Discrete prognostic implication of sarcopenia according to nutritional status in surgically treated patients with hypopharyngeal cancer.

BACKGROUND: Nutritional status and sarcopenia affects the prognosis of head and neck cancers including hypopharyngeal cancer. Hypopharyngeal cancer patients tend to exhibit sarcopenia, which is associated with poor treatment outcomes. This study aims to determine the correlation between nutritional status and sarcopenia, and their prognostic role in surgically treated hypopharyngeal cancer. MATERIALS AND METHODS: Patients who had been diagnosed with squamous cell carcinoma originating from the hypopharynx and underwent surgery between January 2009 and December 2019 were enrolled in this study. The median neutrophil-to-lymphocyte ratio and prognostic nutritional index (PNI) of the cohort were considered the cut-off values. Sarcopenia was evaluated by measuring skeletal muscle index (SMI) at the third lumbar vertebra. Clinical and serological factors predictive of survival outcomes were evaluated. RESULTS: Patients with high PNI showed better 5-year Overall survival (OS) (52.8% vs. 27.2%, p = 0.001) and disease-free survival (DFS) (59.6% vs. 44.6%, p = 0.033) than those with low PNI. Likewise, patients with low SMI showed worse 5-year OS (25.0% vs. 60.9%, p = 0.002) and DFS (42.4% vs. 68.7%, p = 0.034) than patients with high SMI. Among the patients with high PNI, those with sarcopenia displayed significantly worse OS than those with high SMI (78.0% vs. 34.4%, p = 0.049). High PNI with high SMI presented better overall (p = 0.010) and DFS (p = 0.055) than any other group. CONCLUSIONS: Both sarcopenia and PNI were associated with the prognosis of hypopharyngeal cancer. Considering that PNI and sarcopenia indicate the nutritional status, nutritional status may be a significant risk factor. Therefore, nutritional support that ameliorates sarcopenia may improve survival outcomes in surgically treated patients with hypopharyngeal cancer.

Agathobaculum butyriciproducens Shows Neuroprotective Effects in a 6-OHDA-Induced Mouse Model of Parkinson's Disease.

Parkinson's disease (PD) is the second-most prevalent neurodegenerative disease and is characterized by dopaminergic neuronal death in the midbrain. Recently, the association between alterations in PD pathology and the gut microbiota has been explored. Microbiota-targeted interventions have been suggested as a novel therapeutic approach for PD. Agathobaculum butyriciproducens SR79T (SR79) is an anaerobic bacterium. Previously, we showed that SR79 treatment induced cognitive improvement and reduced Alzheimer's disease pathologies in a mouse model. In this study, we hypothesized that SR79 treatment may have beneficial effects on PD pathology. To investigate the therapeutic effects of SR79 on PD, 6-hydroxydopamine (6-OHDA)-induced mouse models were used. D-Amphetamine sulfate (d-AMPH)-induced behavioral rotations and dopaminergic cell death were analyzed in unilateral 6-OHDA-lesioned mice. Treatment with SR79 significantly decreased ipsilateral rotations induced by d-AMPH. Moreover, SR79 treatment markedly activated the AKT/GSK3ß signaling pathway in the striatum. In addition, SR79 treatment affected the Nrf2/ARE signaling pathway and its downstream target genes in the striatum of 6-OHDA-lesioned mice. Our findings suggest a protective role of SR79 in 6-OHDA-induced toxicity by regulating the AKT/Nrf2/ARE signaling pathway and astrocyte activation. Thus, SR79 may be a potential microbe-based intervention and therapeutic strategy for PD.

Humulus japonicus rescues autistic­like behaviours in the BTBR T+ Itpr3tf/J mouse model of autism.

Humulus japonicus (HJ) is a traditional herbal medicine that exhibits anti­inflammatory, antimicrobial and anti­tumor effects that is used for the treatment of hypertension, pulmonary disease and leprosy. Recently, it has also been reported that HJ demonstrates neuroprotective properties in animal models of neurodegenerative diseases. The current study hypothesised that the administration of HJ would exhibit therapeutic effects in autism spectrum disorder (ASD), a neurodevelopmental disorder with lifelong consequences. The BTBR T+ Itpr3tf/J mouse model of ASD was used to investigate the anti­autistic like behavioural effects of HJ. Chronic oral administration of the ethanolic extract of HJ significantly increased social interaction, attenuated repetitive grooming behaviour and improved novel­object recognition in BTBR mice. Anti­inflammatory effects of HJ in the brain were analysed using immunohistochemistry and reverse­transcription quantitative PCR analysis. Microglia activation was markedly decreased in the striatum and hippocampus, and pro­inflammatory cytokines, including C­C Motif Chemokine Ligand 2, interleukin (IL)­1ß and IL­6, were significantly reduced in the hippocampus following HJ treatment. Moreover, HJ treatment normalised the phosphorylation levels of: N­methyl­D­aspartate receptor subtype 2B and calcium/calmodulin­dependent protein kinase type II subunit α in the hippocampus of BTBR mice. The results of the present study demonstrated that the administration of HJ may have beneficial potential for ameliorating behavioural deficits and neuroinflammation in ASD.

Sodium phenylbutyrate reduces repetitive self-grooming behavior and rescues social and cognitive deficits in mouse models of autism.

Autism spectrum disorder (ASD) is a neurodevelopment disorder characterized by deficits in social interaction and restrictive, repetitive, and stereotypical patterns of behavior. However, there is no pharmacological drug that is currently used to target these core ASD symptoms. Sodium phenylbutyrate (NaPB) is a well-known long-term treatment of urea cycle disorders in children. In this study, we assessed the therapeutic effects of NaPB, which is a chemical chaperone as well as histone deacetylase inhibitor on a BTBR T + Itpr3tf/J (BTBR) mice model of ASD. We found that acute and chronic treatment of NaPB remarkably improved, not only core ASD symptoms, including repetitive behaviors and sociability deficit, but also cognitive impairment in the BTBR mice. NaPB substantially induced histone acetylation in the brain of the BTBR mice. Intriguingly, the therapeutic effects of NaPB on autistic-like behaviors, such as repetitive behaviors, impaired sociability, and cognitive deficit also showed in the valproic acid (VPA)-induced mouse model of autism. In addition, pentylenetetrazole (PTZ)-induced seizure was significantly attenuated by NaPB treatment in C57BL/6J and BTBR mice. These findings suggest that NaPB may provide a novel therapeutic approach for the treatment of patients with ASD.

Piperlongumine decreases cognitive impairment and improves hippocampal function in aged mice.

Piperlongumine (PL), a biologically active compound from the Piper species, has been shown to exert various pharmacological effects in a number of conditions, including tumours, diabetes, pain, psychiatric disorders and neurodegenerative disease. In this study, we evaluated the therapeutic effects of PL on hippocampal function and cognition decline in aged mice. PL (50 mg/kg/day) was intragastrically administrated to 23­month­old female C57BL/6J mice for 8 weeks. Novel object recognition and nest building behaviour tests were used to assess cognitive and social functions. Additionally, immunohistochemistry and western blot analysis were performed to examine the effects of PL on the hippocampus. We found that the oral administration of PL significantly improved novel object recognition and nest building behaviour in aged mice. Although neither the percentage area occupied by astrocytes and microglia nor the level of 4­hydroxynonenal protein, a specific marker of lipid peroxidation, were altered by PL treatment, the phosphorylation levels of N­methyl­D­aspartate receptor subtype 2B (NR2B), calmodulin­dependent protein kinase II alpha (CaMKIIα) and extracellular signal­regulated kinase 1/2 (ERK1/2) were markedly increased in the hippocampus of aged mice following the administration of PL. We also found that PL treatment resulted in a CA3­specific increase in the phosphorylation level of cyclic AMP response element binding protein, which is recognized as a potent marker of neuronal plasticity, learning and memory. Moreover, the number of doublecortin­positive cells, a specific marker of neurogenesis, was significantly increased following PL treatment in the dentate gyrus of the hippocampus. On the whole, these data demonstrate that PL treatment may be a potential novel approach in the treatment of age­related cognitive impairment and hippocampal changes.

Effects of histone acetyltransferase inhibitors on L-DOPA-induced dyskinesia in a murine model of Parkinson's disease.

Histone acetylation is a key regulatory factor for gene expression in cells. Modulation of histone acetylation by targeting of histone acetyltransferases (HATs) effectively alters many gene expression profiles and synaptic plasticity in the brain. However, the role of HATs on L-DOPA-induced dyskinesia of Parkinson's disease (PD) has not been reported. Our aim was to determine whether HAT inhibitors such as anacardic acid, garcinol, and curcumin from natural plants reduce severity of L-DOPA-induced dyskinesia using a unilaterally 6-hydroxydopamine (6-OHDA)-lesioned PD mouse model. Anacardic acid 2 mg/kg, garcinol 5 mg/kg, or curcumin 100 mg/kg co-treatment with L-DOPA significantly reduced the axial, limb, and orofacial (ALO) score indicating less dyskinesia with administration of HAT inhibitors in 6-OHDA-lesioned mice. Additionally, L-DOPA's efficacy was not altered by the compounds in the early stage of treatment. The expression levels of c-Fos, Fra-2, and Arc were effectively decreased by administration of HAT inhibitors in the ipsilateral striatum. Our findings indicate that HAT inhibitor co-treatment with L-DOPA may have therapeutic potential for management of L-DOPA-induced dyskinesia in patients with PD.

Effects of different cellulose membranes regenerated from Styela clava tunics on wound healing.

The aim of this study was to investigate the therapeutic effects of three different cellulose membranes (CMs) manufactured from Styela clava tunics (SCTs) on the healing of cutaneous wounds. We examined the physical properties and therapeutic effects of three CMs regenerated from SCTs (referred to as SCT­ CMs), including normal CM (SCT­CM), freeze-dried SCT­CM (FSCT­CM) and sodium alginate-supplemented SCT­CM (ASCT­CM) on skin regeneration and angiogenesis using Sprague-Dawley (SD) rats. FSCT­CM exhibited an outstanding interlayered structure, a high tensile strength (1.64 MPa), low elongation (28.59%) and a low water vapor transmission rate (WVTR) compared with the other SCT-CMs, although the fluid uptake rate was maintained at a medium level. In the SD rats with surgically wounded skin, the wound area and score of wound edge were lower in the FSCT­CM-treated group than in the gauze (GZ)-treated group on days 3-6 and 12-14. In addition, a significant attenuation in the histopathological changes was observed in the FSCT­CM-treated group. Furthermore, the expression level of collagen-1 and the signaling pathway of transforming growth factor (TGF)-ß1 were significantly stimulated by the topical application of FSCT­CM. However, no signs of toxicity were detected in the livers or kidneys of the three SCT­CM-treated groups. Overall, our data indicate that the FSCT­CM may accelerate the process of wound healing in the surgically wounded skin of SD rats through the regulation of angiogenesis and connective tissue formation without inducing any specific toxicity.

Humulus japonicus inhibits the progression of Alzheimer's disease in a APP/PS1 transgenic mouse model.

Humulus japonicus Siebold & Zucc. (HJ) has traditionally been administered to patients with pulmonary disease, skin disease and hypertension in Korea, and it is considered to exert anti-inflammatory, antioxidant, antimicrobial and antimycobacterial effects. However, its effects against Alzheimer's disease (AD) have yet to be explored. Thus, this study was carried out to investigate whether HJ has a beneficial effect on the progression of AD in an animal model. A methanolic extract of HJ (500 mg/kg/day) was intragastrically administered to 5-month-old APP/PS1 transgenic (Tg-APP/PS1) mice for 2.5 months. Novel object recognition and Y-maze alteration tests were used to assess cognitive function, and an immunohistochemical assay was performed to assess amyloid ß (Aß)deposition, tau phosphorylation and gliosis. An in vitro assay using a microglial cell line was also performed to investigate the anti-inflammatory effects of HJ. Our results revealed that HJ significantly decreased the mRNA and protein expression levels of tumor necrosis factor-α (TNF­α), interleukin (IL)-1ß, IL-6 and inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide in the microglial cell line. The administration of HJ for 2 months improved the cognitive function of Tg-APP/PS1 mice. HJ notably reduced the area occupied by Aß and neurofibrillary tangles, and the number of activated astrocytes and microglia in the cortex of Tg-APP/PS1 mice. The findings of our study suggest that HJ has the therapeutic potential to inhibit the progression of AD and to improve cognitive deterioration in Tg-APP/PS1 mice.

Protective effects of the antioxidant extract collected from Styela clava tunics on UV radiation­induced skin aging in hairless mice.

Ultraviolet (UV) radiation is considered a primary cause of skin damage, which is characterized by deep wrinkles, roughness, laxity and pigmentation through oxidative stress and oxidative photodamage. To examine the therapeutic effects of ethanol extract of Styela clava tunics (EtSCT) on UV radiation-induced skin aging in hairless mice, alterations in skin phenotype, histological structures, inflammation, endoplasmic reticulum (ER) stress, oxidative conditions and toxicity were investigated during 13 weeks of UV irradiation and topical application of EtSCT. EtSCT showed high reducing power (3.1%), 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (92.7%) and NO scavenging activity (15.6%) due to its high total flavonoids (15.3 mg/ml) and total phenolics (36.8 mg/ml). The topical application of EtSCT suppressed photoaging of the skin of UV-irradiated mice, and this was demonstrated by the inhibition of wrinkle formation, the suppression of the erythema index as well as the prevention of transepidermal water loss. Additionally, the epidermal thickness and adipocytes number were recovered to a similar level as that in the no radiation group in the UV + EtSCT­treated groups compared with the UV + vehicle­treated group, and the expression of collagen I increased. The attenuation of mitogen­activated protein kinase and ER stress signaling pathways activated by reactive oxygen species was also detected in the UV + EtSCT­treated group. Inflammatory responses including the infiltration of mast cells, CD31 expression and interleukin-6 secretion were significantly lower in the UV + EtSCT-treated groups. Moreover, the concentration of malondialdehyde was reduced and the activity of superoxide dismutase was effectively recovered in the UV + EtSCT-treated groups compared with that in the vehicle-treated groups. Liver and kidney toxicity factors were maintained at a constant level. These results suggest that EtSCT has the potential for use as therapeutic drug which protects against skin aging by regulating the skin morphology, histopathological structures, ER stress, inflammation and oxidative conditions.

Laxative effects of Liriope platyphylla are tightly correlated with suppression of endoplasmic reticulum stress in loperamide-induced constipation of SD rats.

A dysfunction of endoplasmic reticulum (ER) stress response can result in various diseases, including cancer, inflammation, diabetes and neurodegenerative disorders. To investigate whether ER stress response can play an essential role in the induction and treatment of chronic constipation, alterations in the key parameters for ER stress were measured in loperamide (Lop) induced constipation Sprague Dawley (SD) rats treated with aqueous extracts of Liriope platyphylla (AEtLP), which has been shown to have a laxative effect. Symptoms of chronic constipation including alteration of stool parameters and the transverse colon's structure were successfully induced by Lop treatment. Laxative effects such as enhancement of stools parameters, recovery of the mucosa thickness, increased muscle thickness and recovery of flat luminal surface were also observed in the Lop+AEtLP treated group. Furthermore, enhancement of eukaryotic initiation factor 2 alpha (eIF2α) phosphorylation and inositol-requiring enzyme 1 beta (IRE1ß) expression, key indicators for ER stress, that were observed in the Lop+vehicle treated group were significantly recovered in the Lop+AEtLP treated group, although the phosphorylation level of c-Jun N-terminal protein kinase (JNK) remained constant. Moreover, alterations in the transcription level of the marker genes X-box binding protein 1 (XBP-1) and growth arrest and DNA damage-inducible protein (GADD34) were similar to those of eIF2α and IRE1ß. However, their level was slightly or completely recovered after AEtLP treatment. Overall, this study provides the first evidence that ER stress response may be tightly correlated with chronic constipation induced by Lop treatment, as well as the laxative effects of AEtLP.

Therapeutic effect of ethyl acetate extract from Asparagus cochinchinensis on phthalic anhydride-induced skin inflammation.

Asparagus cochinchinensis has been used to treat various diseases including fever, cough, kidney disease, breast cancer, inflammatory disease and brain disease, while IL-4 cytokine has been considered as key regulator on the skin homeostasis and the predisposition toward allergic skin inflammation. However, few studies have investigated its effects and IL-4 correlation on skin inflammation to date. To quantitatively evaluate the suppressive effects of ethyl acetate extracts of A. cochinchinensis (EaEAC) on phthalic anhydride (PA)-induced skin inflammation and investigate the role of IL-4 during their action mechanism, alterations in general phenotype biomarkers and luciferase-derived signals were measured in IL-4/Luc/CNS-1 transgenic (Tg) mice with PA-induced skin inflammation after treatment with EaEAC for 2 weeks. Key phenotype markers including lymph node weight, immunoglobulin E (IgE) concentration, epidermis thickness and number of infiltrated mast cells were significantly decreased in the PA+EaEAC treated group compared with the PA+Vehicle treated group. In addition, expression of IL-1ß and TNF-α was also decreased in the PA+EaEAC cotreated group, compared to PA+Vehicle treated group. Furthermore, a significant decrease in the luciferase signal derived from IL-4 promoter was detected in the abdominal region, submandibular lymph node and mesenteric lymph node of the PA+EaEAC treated group, compared to PA+Vehicle treated group. Taken together, these results suggest that EaEAC treatment could successfully improve PA-induced skin inflammation of IL-4/Luc/CNS-1 Tg mice, and that IL-4 cytokine plays a key role in the therapeutic process of EaEAC.

Diosgenin effectively suppresses skin inflammation induced by phthalic anhydride in IL-4/Luc/CNS-1 transgenic mice.

To quantitatively evaluate the therapeutic effects of diosgenin (DG) and investigate the role of IL-4 on skin inflammation, alterations in luciferase-derived signal and general phenotype biomarkers were measured in IL-4/Luc/CNS-1 transgenic mice with phthalic anhydride (PA)-induced skin inflammation after treatment with DG for 4 weeks. High levels of luciferase-derived signal detected in the abdominal region and submandibular lymph node (SL) of the PA treated group was significantly decreased by 67-88% in the PA + DG cotreated group. Furthermore, the weight of the lymph node and spleen, IgE concentration, epidermis thickness, and number of infiltrated mast cells were lower in the PA + DG treated group than the PA + Vehicle treated group. Moreover, expression of IL-6 and vascular endothelial growth factor (VEGF) also decreased in the PA + DG cotreated group. These results suggest that PA-induced skin inflammation could be successfully suppressed by DG treatment in IL-4/Luc/CNS-1 Tg mice through attenuation of IL-4 and IL-6 expression, as well as decreased IgE concentration and mast cells infiltration.

Protective Effect of Gallotannin-Enriched Extract Isolated from Galla Rhois against CCl4-Induced Hepatotoxicity in ICR Mice.

To investigate the toxicity, protective effects, and action mechanism of gallotannin-enriched extracts isolated from Galla Rhois (GEGR) against carbon tetrachloride (CCl4)-induced hepatotoxicity in Institute for Cancer Research (ICR) mice, alterations in serum biochemical indicators, histopathological structure, antioxidative status, hepatic apoptosis-related proteins, and liver fibrosis regulating factors were measured in mice pretreated with GEGR for five days before CCl4 injection. The GEGR/CCl4 treated group showed decreased levels of three serum marker enzymes (ALP, AST, and ALT) representing liver toxicity, although LDH levels remained constant. Necrotic area indicating hepatic cell death significantly inhibited, while malondialdehyde (MDA) concentration and superoxide dismutase (SOD) expression were dramatically recovered in the GEGR preadministrated group. In mechanism analyses of GEGR, the formation of active caspase-3 and enhancement of Bax/Bcl-2 expression was effectively inhibited in the GEGR/CCl4 treated group. The level of pro-inflammatory cytokines, TNF-α and IL-6, as well as the phosphorylation of p38 and JNK in the TNF-α downstream signaling pathway was rapidly recovered in the GEGR/CCl4 treated group, while anti-inflammatory cytokine (IL-10) increased slightly in the same group. Furthermore, the GEGR/CCl4 treated group showed a significant decrease in collagen accumulation results from alleviation of MMP-2 expression, TGF-ß1 secretion and the phosphorylation of Smad2/3. Taken together, these results suggest that GEGR may induce remarkable protective effects against hepatic injury induced by CCl4 treatment through upregulation of the anti-inflammatory and antioxidant system.

Gadd45ß ameliorates L-DOPA-induced dyskinesia in a Parkinson's disease mouse model.

The dopamine precursor 3,4-dihydroxyphenyl-l-alanine (L-DOPA) is currently the most efficacious pharmacotherapy for Parkinson's disease (PD). However, long-term L-DOPA treatment leads to the development of abnormal involuntary movements (AIMs) in patients and animal models of PD. Recently, involvement of growth arrest and DNA damage-inducible 45ß (Gadd45ß) was reported in neurological and neurobehavioral dysfunctions. However, little is known about the role of Gadd45ß in the dopaminergic nigrostriatal pathway or L-DOPA-induced dyskinesia (LID). To address this issue, we prepared an animal model of PD using unilateral 6-hydroxydopamine (6-OHDA) lesions in the substantia nigra of Gadd45ß(+/+) and Gadd45ß(-/-) mice. Dyskinetic symptoms were triggered by repetitive administration of L-DOPA in these 6-OHDA-lesioned mice. Whereas dopamine denervation in the dorsal striatum decreased Gadd45ß mRNA, chronic L-DOPA treatment significantly increased Gadd45ß mRNA expression in the 6-OHDA-lesioned striatum of wild-type mice. Using unilaterally 6-OHDA-lesioned Gadd45ß(+/+) and Gadd45ß(-/-) mice, we found that mice lacking Gadd45ß exhibited long-lasting increases in AIMs following repeated administration of L-DOPA. By contrast, adeno-associated virus-mediated expression of Gadd45ß in the striatum reduced AIMs in Gadd45ß knockout mice. The deficiency of Gadd45ß in LID increased expression of ΔFosB and c-Fos in the lesioned striatum 90 min after the last administration of L-DOPA following 11days of daily L-DOPA treatments. These data suggest that the increased expression of Gadd45ß induced by repeated administration of L-DOPA may be beneficial in patients with PD.

Neuroprotective effects of fermented soybean products (Cheonggukjang) manufactured by mixed culture of Bacillus subtilis MC31 and Lactobacillus sakei 383 on trimethyltin-induced cognitive defects mice.

OBJECTIVES: This study aimed to investigate the beneficial effects of Cheonggukjang (CGK) manufactured by mixed culture of Bacillus subtilis MC31 and Lactobacillus sakei 383 on neurotoxic damages. METHODS: The specific aspects of brain functions were measured in Institute for Cancer Research (ICR) mice that had been pretreated for 4 weeks with three difference doses of CGK before trimethyltin (TMT) treatment. RESULTS: The short- and long-term memory loss induced by TMT treatment was significantly improved in the CGK-pretreated group in a dose-dependent manner. The number of dead cells in the granule cell layer of the dentate gyrus was decreased in the TMT/CGK-cotreated group relative to the TMT/vehicle-treated group, whereas significant suppression of acetylcholinesterase (AChE) activity was observed in the same group. Additionally, a dose-dependent increase in nerve growth factor (NGF) concentration, activation of the NGF receptor signaling pathway including the TrkA high affinity receptor and p75(NTR) low affinity receptor, and decline in Bax/Bcl-2 level was measured in all TMT/CGK-treated groups, although a decrease in the active form of caspase-3 was observed in the TMT/H-CGK-treated group. Furthermore, superoxide dismutase (SOD) activity was enhanced in the TMT/CGK-treated group, whereas the level of malondialdehyde (MDA), a marker of lipid peroxidation, was 43-58% lower in the TMT/CGK-treated group than the TMT/vehicle-treated group. DISCUSSION: These results demonstrate that CGK fermented by mixed culture of B. subtilis and L. sakei could exert a wide range of beneficial activities for neurodegenerative diseases, including Alzheimer, Parkinson, and Huntington disease.

Transdermal treatment of the surgical and burned wound skin via phytochemical-capped gold nanoparticles.

The biological activities and therapeutic potential of phytochemical-decorated Au nanoparticles (Phyto-AuNPs) were investigated through the treatment of Phyto-AuNPs on the dorsal skin of rats via transdermal drug delivery process in order to regenerate surgical wounded and burned skin. Two different Phyto-AuNPs were applied to the dorsal skin: gallic acid-isoflavone--covered AuNPs (GI-AuNPs) and protocatechuic acid-isoflavone--covered AuNPs (PI-AuNPs). From the biological activity monitoring, it has been resulted that 5-fold thicker epidermis (ER), 50% reduction of metalloproteinase-1 (MMP-1) level, 3-fold higher superoxide dismutase (SOD) activity were obtained in the Phyto-AuNP-treated group, compared with a vehicle group (deionized water (DI-water) treatment). Moreover, the Phyto-AuNPs treatment on the surgical and burn damaged Sprague-Dawley (SD) rats induced higher expression of vascular endothelial growth factor (VEGF) and angiopoietin-2 (Ang-2). It would be plausible that antioxidant property of Phyto-AuNPs assist the acceleration and activation of biomolecules in the healing mechanism, where Phyto-AuNPs can be potential candidates for skin regeneration and wound healing.

Accelerated healing of cutaneous wounds using phytochemically stabilized gold nanoparticle deposited hydrocolloid membranes.

Rapid healing of dermatological wounds is of vital importance in preventing infection and reducing post-treatment side-effects. Here we report the therapeutic effects of phytochemically stabilized gold nanoparticles (pAuNPs) coated on a hydrocolloid membrane (HCM) for curing cutaneous wounds. Furthermore, the remedial effects of pAuNPs on skin regeneration and angiogenesis were examined using Sprague Dawley® (SD) rats with skin injuries after a pAuNP-deposited hydrocolloid membrane (pAuNP-HCM) had been applied for 15 days. The rate of wound closure was 4 times faster in the pAuNP-HCM-treated group than in the gauze (GZ)- or HCM-treated groups in the first 5 days. Moreover, wound widths in the pAuNP-HCM-treated group were significantly reduced after 5-15 days of treatment following the injury, compared with the other groups. In addition, a significant increase in collagen expression and a decrease in matrix metalloproteinase (MMP)-1 expression and transforming growth factor (TGF-ß1) concentration were observed in the pAuNP-HCM-treated group on day 5. Wound tissue applied with the pAuNP-HCM showed enhancement of vascular endothelial growth factor (VEGF), angiopoietin 1 (Ang-1), and angiopoietin 2 (Ang-2) expression. Furthermore, the activity of superoxide dismutases (SODs) was significantly increased in the skin tissue of the pAuNP-HCM-treated group, compared with the GZ- or HCM-treated groups. It is probable that the accelerated process of wound healing in the injured skin of SD rats via pAuNP-HCM results from the synergistic regulation of angiogenesis and connective tissue formation, as well as the stimulation of antioxidant effects.

Bacterial cellulose membrane produced by Acetobacter sp. A10 for burn wound dressing applications.

Bacteria cellulose membranes (BCM) are used for wound dressings, bone grafts, tissue engineering, artificial vessels, and dental implants because of their high tensile strength, crystallinity and water holding ability. In this study, the effects of BCM application for 15 days on healing of burn wounds were investigated based on evaluation of skin regeneration and angiogenesis in burn injury skin of Sprague-Dawley (SD) rats. BCM showed a randomly organized fibrils network, 12.13 MPa tensile strength, 12.53% strain, 17.63% crystallinity, 90.2% gel fraction and 112.14 g × m(2)/h highest water vapor transmission rate (WVTR) although their swelling ratio was enhanced to 350% within 24h. In SD rats with burned skin, the skin severity score was lower in the BCM treated group than the gauze (GZ) group at all time points, while the epidermis and dermis thickness and number of blood vessels was greater in the BCM treated group. Furthermore, a significant decrease in the number of infiltrated mast cells and in vascular endothelial growth factor (VEGF) and angiopoietin-1 (Ang-1) expression was observed in the BCM treated group at day 10 and 15. Moreover, a significant high level in collagen expression was observed in the BCM treated group at day 5 compared with GZ treated group, while low level was detected in the same group at day 10 and 15. However, the level of metabolic enzymes representing liver and kidney toxicity in the serum of BCM treated rats was maintained at levels consistent with GZ treated rats. Overall, BCM may accelerate the process of wound healing in burn injury skin of SD rats through regulation of angiogenesis and connective tissue formation as well as not induce any specific toxicity against the liver and kidney.

Characterization of allergic response induced by repeated dermal exposure of IL-4/Luc/CNS-1 transgenic mice to low dose formaldehyde.

Although formaldehyde (FA) is known to be a major allergen responsible for allergic contact dermatitis, there are conflicting reports regarding correlation between FA exposure and interleukin (IL-4) expression. To investigate whether allergic responses including IL-4 expression were induced by repeated dermal exposure to low dose FA, alterations in the luciferase signal and allergic phenotypes were measured in IL-4/Luc/CNS-1 transgenic (Tg) mice containing luciferase cDNA under control of the IL-4 promoter after exposure to 4% FA for 2 weeks. High levels of luciferase were detected in the abdominal region of the whole body and submandibular lymph node (SLN) of FA treated mice. Additionally, the ear thickness and IgE concentration were significantly upregulated in the FA treated group when compared with the acetone olive oil (AOO) treated group. FA treated mice showed enhanced auricular lymph node (ALN) weight, epidermis and dermis thickness, and infiltration of inflammatory cells. Furthermore, the expression of IL-6 among T helper 2 cytokines was higher in the FA treated group than the AOO treated group, while vascular endothelial growth factor (VEGF) levels remained constant. Overall, the results presented herein provide additional evidence that various allergic responses may be successfully induced in IL-4/Luc/CNS-1 Tg mice after exposure to low dose FA for 2 weeks. The luciferase signal under the IL-4 promoter may reflect general indicators of the allergic response induced by exposure to low dose FA.

Selenium treatment significantly inhibits tumor necrosis factor-α-induced cell death and tau hyperphosphorylation in neuroblastoma cells.

The hyperphosphorylation of the protein tau disrupts its normal function on regulating axonal transport and leads to the accumulation of neurofibrillary tangles (NFT), which are involved in the pathogenesis of Alzheimer's disease (AD). This study was performed to investigate whether sodium selenite may inhibit the hyperphosphorylation of tau induced by treatment with tumor necrosis factor­α (TNF­α). For this purpose, we studied the changes in cell viability, tau phosphorylation and activity of tau kinases in TNF­α+selenite-treated neuroblastoma cells. Cell viability was significantly recovered in the group cotreated with TNF­α and 5 µM selenite for 24 h, but not in the groups treated with TNF­α and lower concentrations of selenite. Tau phosphorylation was significantly higher in the group treated with TNF­α+vehicle (instead of selenite) compared to the non­treated group. However, in the TNF­α+selenite­treated group, the total phosphorylation level of tau protein at the Ser404 site was significantly reduced compared to the TNF­α+vehicle group, although western blot analysis revealed one band of increased intensity in the p­tau sample, corresponding to a phosphorylated tau isoform of 65­70 kDa. In addition, sodium selenite treatment led to a significant recovery in the immunofluorescence intensity of the p­tau protein in the cytoplasm and nucleus and in the apoptotic rate of neuroblastoma cells stained with the p­tau antibody and 4',6­diamidino­2­phenylindole (DAPI). The phosphorylation of two protein kinases responsible for phosphorylation of tau, glycogen synthase kinase 3ß (GSK­3ß) and Akt, also known as protein kinase B, was markedly decreased in the TNF­α+selenite­treated group relative to the TNF­α+vehicle­treated group. Overall, these results provide strong evidence that sodium selenite (selenium) can inhibit cell death and tau phosphorylation induced by TNF­α in neuroblastoma cells, through the inhibition GSK­3ß and Akt phosphorylation.