Lipid-based nanoformulation optimization for achieving cutaneous targeting: Niosomes as the potential candidates to fulfill this aim.

The present study screened the utility of topically-applied nanoformulations to target the drugs/actives into the skin reservoir with the reduction of possible systemic absorption. The lipid-based nanoformulations selected in this study included solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), nanoemulsions (NEs), liposomes, and niosomes. We loaded flavanone and retinoic acid (RA) as the penetrants. The prepared nanoformulations were assessed for their average diameter, polydispersity index (PDI), and zeta potential. An in vitro permeation test (IVPT) was utilized to determine the skin delivery into/across pig skin, atopic dermatitis (AD)-like mouse skin, and photoaged mouse skin. We found an increased skin absorption of lipid nanoparticles following the increase of solid lipid percentage in the formulations (SLNs > NLCs > NEs). The use of liposomes even reduced the dermal/transdermal selectivity (S value) to lessen the cutaneous targeting. The niosomes resulted in significantly greater RA deposition and reduced permeation in the Franz cell receptor compared to the other nanoformulations. The S value of the RA delivery via stripped skin was increased by 26-fold in the niosomes compared to the free RA. The dye-labeled niosomes displayed a strong fluorescence in the epidermis and upper dermis through the visualization of fluorescence and confocal microscopies. The cyanoacrylate skin biopsy manifested greater hair follicle uptake of the niosomes compared to the free penetrants by 1.5 to three-fold. The 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay indicated an increase in antioxidant ability from 55% to 75% after flavanone entrapment in the niosomes. In the activated keratinocytes, the niosomal flavanone could suppress the overexpressed CCL5 to the baseline control because of the facile cell internalization. After the formulation optimization, the niosomes with higher phospholipid amount had a superior effect in delivering penetrants into the skin reservoir, with limited permeation to the receptors.

Evaluation of the Anti-Atopic Dermatitis Effects of α-Boswellic Acid on Tnf-α/Ifn-γ-Stimulated HaCat Cells and DNCB-Induced BALB/c Mice.

Boswellic acids, triterpenoids derived from the genus Boswellia (Burseraceae), are known for their anti-inflammatory and anti-tumor efficacy. Atopic dermatitis is a chronic, non-infectious inflammatory skin disease. However, the effects of α-boswellic acid on atopic dermatitis have not been studied. Therefore, in this study we examined the expression level of pro-inflammatory cytokines, histopathological analysis, and physiological data from BALB/c mice with atopic-like dermatitis induced by 2,4-dinitrochlorobenzene and TNF-α/IFN-γ-stimulated HaCaT cells to better understand the agent's anti-atopic dermatitis efficacy. First, we found that α-boswellic reduced the epidermal thickening, mast cell numbers, and dermal infiltration of 2,4-dinitrochlorobenzene-induced atopic-like dermatitis in BALB/c mice. Furthermore, we also found that α-boswellic acid can restore transepidermal water loss and skin reddening in mice. In human keratinocytes inflamed by TNF-α/IFN-γ, α-boswellic acid inhibited MAP kinase activation and showed a reduction in NF-κB nuclear translocation. Finally, α-boswellic acid can reduce the expression level of cytokines (IL-1ß, IL-6, and IL-8) following the stimulation of TNF-α/IFN-γ in HaCaT cells. Taken together, our study suggests that α-boswellic acids are a potential component for the development of anti-atopic dermatitis drugs.

Anti-Inflammatory Effects of Cycloheterophyllin on Dinitrochlorobenzene-Induced Atopic Dermatitis in HaCaT Cells and BALB/c Mice.

Atopic dermatitis (eczema) is a condition that makes skin red and itchy. Though common in children, the condition can occur at any age. Atopic dermatitis is persistent (chronic) and tends to recur periodically. It may be accompanied by asthma or hay fever. No cure has been found for eczema. Therefore, it is very important to develop ingredients that aid the prevention and treatment of atopic dermatitis. Cycloheterophyllin is derived from Artocarpus heterophyllus and has antioxidant and anti-inflammatory activities. However, it still is not understood whether cycloheterophyllin is an anti-atopic dermatitis agent. Keratinocytes (HaCaT cells) and BALB/c mice for inducing AD-like cutaneous lesions were used to evaluate the potential of cycloheterophyllin as an anti-atopic dermatitis agent. The release of pro-inflammatory cytokines induced by treatment of TNF-α/IFN-γ was reduced after pretreatment with cycloheterophyllin. The inhibitory effects could be a contribution from the effect of the MAP kinases pathway. Moreover, the symptoms of atopic dermatitis (such as red skin and itching) were attenuated by pretreatment with cycloheterophyllin. Epidermal hyperplasia and mast cell infiltration were decreased in the histological section. Finally, damage to the skin barrier was also found to recover through assessment of transepidermal water loss. Taken together, prenylflavone-cycloheterophyllin from Artocarpus heterophyllus is a potential anti-atopic dermatitis ingredient that can be used in preventing or treating the condition.

Urolithin A Inactivation of TLR3/TRIF Signaling to Block the NF-κB/STAT1 Axis Reduces Inflammation and Enhances Antioxidant Defense in Poly(I:C)-Induced RAW264.7 Cells.

Urolithin A is an active compound of gut-microbiota-derived metabolites of polyphenol ellagic acid that has anti-aging, antioxidative, and anti-inflammatory effects. However, the effects of urolithin A on polyinosinic acid-polycytidylic acid (poly(I:C))-induced inflammation remain unclear. Poly(I:C) is a double-stranded RNA (dsRNA) similar to a virus and is recognized by Toll-like receptor-3 (TLR3), inducing an inflammatory response in immune cells, such as macrophages. Inflammation is a natural defense process of the innate immune system. Therefore, we used poly(I:C)-induced RAW264.7 cells and attenuated the inflammation induced by urolithin A. First, our data suggested that 1-30 µM urolithin A does not reduce RAW264.7 cell viability, whereas 1 µM urolithin A is sufficient for antioxidation and the decreased production of tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), and C-C chemokine ligand 5. The inflammation-related proteins cyclooxygenase-2 and inducible nitric oxide synthase were also downregulated by urolithin A. Next, 1 µM urolithin A inhibited the levels of interferon (INF)-α and INF-ß. Urolithin A was applied to investigate the blockade of the TLR3 signaling pathway in poly(I:C)-induced RAW264.7 cells. Moreover, the TLR3 signaling pathway, subsequent inflammatory-related pathways, and antioxidation pathways showed changes in nuclear factor-κB (NF-κB) signaling and blocked ERK/mitogen-activated protein kinase (MAPK) signaling. Urolithin A enhanced catalase (CAT) and superoxide dismutase (SOD) activities, but decreased malondialdehyde (MDA) levels in poly(I:C)-induced RAW264.7 cells. Thus, our results suggest that urolithin A inhibits TLR3-activated inflammatory and oxidative-associated pathways in macrophages, and that this inhibition is induced by poly(I:C). Therefore, urolithin A may have antiviral effects and could be used to treat viral-infection-related diseases.

Pharmacological Role of Functionalized Gold Nanoparticles in Disease Applications.

Gold has always been regarded as a symbol of nobility, and its shiny golden appearance has always attracted the attention of many people. Gold has good ductility, molecular recognition properties, and good biocompatibility. At present, gold is being used in many fields. When gold particles are as small as several nanometers, their physical and chemical properties vary with their size in nanometers. The surface area of a nano-sized gold surface has a special effect. Therefore, gold nanoparticles can, directly and indirectly, give rise to different biological activities. For example, if the surface of the gold is sulfided. Various substances have a strong chemical reactivity and are easy to combine with sulfhydryl groups; hence, nanogold is often used in biomedical testing, disease diagnosis, and gene detection. Nanogold is easy to bind to proteins, such as antibodies, enzymes, or cytokines. In fact, scientists use nanogold to bind special antibodies, as a tool for targeting cancer cells. Gold nanoparticles are also directly cytotoxic to cancer cells. For diseases caused by inflammation and oxidative damage, gold nanoparticles also have antioxidant and anti-inflammatory effects. Based on these unique properties, gold nanoparticles have become the most widely studied metal nanomaterials. Many recent studies have further demonstrated that gold nanoparticles are beneficial for humans, due to their functional pharmacological properties in a variety of diseases. The content of this review will be the application of gold nanoparticles in treating or diagnosing pressing diseases, such as cancers, retinopathy, neurological diseases, skin disorders, bowel diseases, bone cartilage disorders, cardiovascular diseases, infections, and metabolic syndrome. Gold nanoparticles have shown very obvious therapeutic and application potential.

Cutaneous Delivery of Cosmeceutical Peptides Enhanced by Picosecond- and Nanosecond-Domain Nd:YAG Lasers with Quick Recovery of the Skin Barrier Function: Comparison with Microsecond-Domain Ablative Lasers.

Picosecond or nanosecond-domain non-ablative lasers generate faster photothermal effects and cause less injury than microsecond lasers. In this study, we investigated the enhancing effect of 1064 nm picosecond- and nanosecond-domain neodymium (Nd):yttrium-aluminum-garnet (YAG) lasers on the cutaneous delivery of cosmeceutical peptides. Microsecond-domain fractional ablative CO2 and fully ablative erbium (Er):YAG lasers were also used for comparison. In the Franz diffusion cell study, pig or mouse skin was treated with a laser before exposure to palmitoyl tripeptide (PT)-1, PT-38, and copper tripeptide (CT)-1 at a concentration of 150 µM. Psoriasiform, atopic dermatitis (AD)-like, and photoaged skins were also developed as permeation barriers. The non-ablative laser elicited the ultrastructural disruption of the stratum corneum and epidermal vacuolation. All laser modalities significantly increased the skin permeation of peptides in vitro. The non-ablative laser chiefly enhanced peptide delivery to the receptor compartment, whereas the ablative laser mainly increased the intracutaneous peptide deposition. The picosecond- and nanosecond-domain Nd:YAG lasers elevated the amount of PT-1 in the receptor up to 40- and 22-fold compared with untreated skin, respectively. Laser treatment promoted peptide delivery in barrier-deficient and inflamed skins, although this enhancement effect was less than that observed in healthy skin. Fluorescence microscopy indicated the capability of the non-ablative laser to deliver peptides to deeper skin strata. The ablative laser confined the peptide distribution in the epidermis. Confocal microscopy showed that peptides penetrated the skin along the microdots created by the fractional Nd:YAG and CO2 lasers. The skin barrier function determined by transepidermal water loss suggested quick recovery when using a nanosecond-domain laser (within 4 h). A longer period was needed for the skin treated with the fully ablative Er:YAG laser (76-84 h). Nanosecond non-ablative laser-facilitated peptide delivery may become an efficient and safe approach for cosmeceutical applications.

Low-fluence laser-facilitated platelet-rich plasma permeation for treating MRSA-infected wound and photoaging of the skin.

Platelet-rich plasma (PRP) is rich in cytokines and growth factors and is a novel approach for tissue regeneration. It can be used for skin rejuvenation but the large molecular size of the actives limits its topical application. In this study, low-fluence laser-facilitated PRP was delivered to evaluate its effect on absorption through the skin, infection-induced wound, and photoaging. The PRP permeation enhancement was compared for two ablative lasers: fractional (CO2) laser and fully-ablative (Er:YAG) laser. In the Franz cell experiment, pig skin was treated with lasers with superficial ablation followed by the application of recombinant cytokines, growth factors, or PRP. The transport of interferon (IFN)-γ and tumor necrosis factor (TNF)-α was negligible in intact skin and stratum corneum (SC)-stripped skin. Both lasers significantly elevated skin deposition of IFN-γ and TNF-α from PRP, and fully-ablative laser showed a higher penetration enhancement. A similar tendency was found for vascular endothelial growth factor and epidermal growth factor. Er:YAG laser-exposed skin displayed 1.8- and 3.9-fold higher skin deposition of platelet-derived growth factor (PDGF)-BB and transforming growth factor (TGF)-ß1 from PRP, respectively. According to the confocal images, both laser interventions led to an extensive and deep distribution of IFN-γ and PDGF-BB in the skin. In the in vivo methicillin-resistant Staphylococcus aureus (MRSA) infection model, CO2 laser- and Er:YAG laser-assisted PRP delivery reduced bacterial load from 1.8 × 106 to 5.9 × 105 and 1.4 × 104 colony-forming units, respectively. The open wound induced by MRSA was closed by the laser-assisted PRP penetration. In the mouse photoaging model, elastin and collagen deposition were fully restored by combined PRP and full-ablative laser but not by PRP alone and PRP combined with fractional laser. Laser-facilitated PRP delivery even with a low fluence setting can be considered a promising strategy for treating some dermatological disorders.

Luteolin Attenuates IL-1ß-Induced THP-1 Adhesion to ARPE-19 Cells via Suppression of NF-κB and MAPK Pathways.

Cytokine-induced endothelial dysfunction leads to inflammation and vascular adhesion molecule production in retinal pigment epithelium (RPE) cells. Inflammation is a critical mediator in retinal degeneration (RD) diseases, including age-related macular degeneration (AMD), and RD progression may be prevented through anti-inflammatory activity in RPE cells. The flavonoid polyphenol luteolin (LU) has anti-inflammatory and antidiabetes activities, but its effects regarding retinal protection remain unknown. Here, we examined the ability of luteolin to alleviate markers of inflammation related to RD in cytokine-primed APPE-19 cells. We found that luteolin decreased the levels of interleukin- (IL-) 6, IL-8, soluble intercellular adhesion molecule-1 (sICAM-1), and monocyte chemoattractant protein-1 (MCP-1) and attenuated adherence of the human monocytic leukemia cell line THP-1 to IL-1ß-stimulated ARPE-19 cells. Luteolin also increased anti-inflammatory protein heme oxygenase-1 (HO-1) levels. Interestingly, luteolin induced protein kinase B (AKT) phosphorylation, thus inhibiting nuclear factor- (NF-) κB transfer from cytoplasm into the nucleus and suppressing mitogen-activated protein kinase (MAPK) inflammatory pathways. Furthermore, cotreatment with MAPK inhibitors and luteolin decreased inflammatory cytokine and chemokine levels, and further suppressed THP-1 adhesion. Overall, these results provide evidence that luteolin protects ARPE-19 cells from IL-1ß-stimulated increases of IL-6, IL-8, sICAM-1, and MCP-1 production by blocking the activation of MAPK and NF-κB signaling pathways, thus ameliorating the inflammatory response.

An isoflavone extract from soybean cake suppresses 2,4-dinitrochlorobenzene-induced contact dermatitis.

ETHNOPHARMACOLOGICAL RELEVANCE: Numerous epidemiological and clinical studies have demonstrated the protective role of dietary isoflavones against development of several chronic diseases. ISO-1, one fraction of isoflavone powders derived from soybean cake, is reported to attenuate inflammation and photodamage. AIM OF THE STUDY: Contact dermatitis is a common inflammatory skin disease, which accounts for most occupational skin disorders. Instead of oral administration, we aimed to explore the effects of topical ISO-1 application on contact dermatitis by using 2,4-dinitrochlorobenzene (DNCB)-stimulated HaCaT keratinocytes and DNCB-induced mouse dermatitis as models. MATERIALS AND METHODS: In the in vitro study, we first evaluated the biologic effects of DNCB on HaCaT keratinocytes. HaCaT keratinocytes were treated with 2,4-dinitrochlorobenzene (DNCB), and cell viability was measured by MTT assay. Then, we detect the prominent induction of IL-8 mRNA expression after DNCB and ISO-1 treatment by reverse transcription polymerase chain reaction (RT-PCR), and release of IL-8 from HaCaT keratinocytes was measured by ELISA assay. HaCaT keratinocytes were pretreated with ISO-1 and then treated with DNCB, phosphorylation of JNK, p38, ERK and IκBα was analyzed by western blot. In the in vivo study, the hairless mice were used for an induced contact dermatitis model. The surface changes in the dorsal skin after DNCB and ISO-1 treatment were recorded using photography, and TEWL, erythema were measured using an MPA-580 cutometer. Blood was also collected from mice for measurement of white blood cell counts. RESULTS: Results showed ISO-1 inhibited DNCB-induced IL-8 production and also suppressed DNCB-induced phosphorylation of JNK and p38, and IκBα in HaCaT. In the animal model of DNCB-induced contact dermatitis, topical ISO-1 treatment significantly decreased DNCB-induced erythema and transepidermal water loss (TEWL) in mouse skin. ISO-1 also reduced DNCB-induced skin thickening and increase of white blood cell count. CONCLUSIONS: ISO-1 is promising for improvement of DNCB-induced inflammation and skin barrier impairment, suggesting the potential application of topical ISO-1 for inflammatory dermatoses.

Supplementation of nano-bubble curcumin extract improves gut microbiota composition and exercise performance in mice.

BACKGROUND: In a previous study, we evaluated the potential beneficial effect of nano-bubble curcumin extract (NCE) in reducing exercise-related injuries and improving performance. METHODS: In this study, we seek to investigate changes in the gut microbiota composition upon NCE supplementation in relation to health and exercise performance. Male ICR mice were divided into 3 groups (n = 8 per group) and orally administered NCE once daily for six weeks at 0 (vehicle), 3.075 (NCE-1X) and 15.375 g kg-1 day-1 (NCE-5X). The gut microbiota from the mice was analyzed using 16S rRNA gene sequencing. RESULTS: NCE-5X did not appear to obviously cluster with the vehicle group, although NCE-5X groups showed an increased Firmicutes/Bacteroidetes ratio compared with the vehicle group. In addition, anti-fatigue activity and exercise performance were evaluated by investigating the exhaustive swimming time, forelimb grip strength and serum levels of lactate, ammonia, glucose, blood urea nitrogen (BUN), creatine kinase (CK) and lactate dehydrogenase (LDH) after swimming. The NCE-1X and NCE-5X groups showed a significantly longer exhaustive swimming time and higher relative forelimb grip strength than the vehicle group. Tissue glycogen content, an important energy source for exercise, increased significantly with NCE supplementation. CONCLUSION: Taken together, our results indicate that NCE supplementation alters the gut microbiota composition and aids in overcoming physical fatigue. Curcumin may be acting on the gut microbiome to modulate the gut system towards improving exercise performance.

Development of flavanone and its derivatives as topical agents against psoriasis: The prediction of therapeutic efficiency through skin permeation evaluation and cell-based assay.

Flavonoids inhibit skin inflammation. Previous study suggests that the flavonoids with flavanone backbone were beneficial to penetrate into the skin. We aimed to investigate the possibility of psoriasis treatment by topically applied flavanone and its derivatives including naringenin, hesperetin, 6-hydroxyflavanone, flavanone, and 6-bromoflavone. The skin absorption of the compounds was determined by Franz cells. Molecular modeling was used to compute the physicochemical and molecular parameters of the penetrants in order to elucidate the correlation between structure and permeation. Among the compounds tested, flavanone showed the greatest skin absorption. The in vitro skin absorption predicted efficient skin targeting of 6-bromoflavone with minimal risk of circulation absorption. The permeation of naringenin was remarkably enhanced 13-fold in the barrier-defective skin mimicking inflamed skin. The penetrants with fewer hydrogen bond number, total polarity surface, and molecular volume were advantageous for facile skin absorption. In the cell-based study, IL-1ß inhibition in imiquimod (IMQ)-stimulated keratinocytes was increased following the increase in compound lipophilicity. Naringenin, a flavanone analog with three hydroxyl moieties, could suppress IL-6 overexpression to baseline control. We assessed the anti-inflammatory potency of the chemicals in comparison with tacrolimus as reference in a psoriasis-like mouse model. Flavanone was found to mitigate scaling and epidermal hyperplasia at a higher level than naringenin. Flavanone lessened IL-6 overexpression by 80% in the psoriasiform plaque. The skin barrier function recorded by transepidermal water loss (TEWL) was recovered by naringenin but not flavanone. The experimental data indicate that naringenin and flavanone are potential candidates for anti-psoriatic therapy.

Chrysin alleviates imiquimod-induced psoriasis-like skin inflammation and reduces the release of CCL20 and antimicrobial peptides.

Psoriasis is a common non-contagious chronic inflammatory skin lesion, with frequent recurrence. It mainly occurs due to aberrant regulation of the immune system leading to abnormal proliferation of skin cells. However, the pathogenic mechanisms of psoriasis are not fully understood. Although most of the current therapies are mostly efficient, the side effects can result in therapy stop, which makes the effectiveness of treatment strategies limited. Therefore, it is urgent and necessary to develop novel therapeutics. Here, we investigated the efficacy of chrysin, a plant flavonoid, which we previously reported to possess strong antioxidant and anti-inflammatory effects, against psoriasis-like inflammation. Our results revealed that chrysin significantly attenuated imiquimod-induced psoriasis-like skin lesions in mice, and improved imiquimod-induced disruption of skin barrier. Moreover, the TNF-α, IL-17A, and IL-22-induced phosphorylation of MAPK and JAK-STAT pathways, and activation of the NF-κB pathway were also attenuated by chrysin pretreatment of epidermal keratinocytes. Most importantly, chrysin reduced TNF-α-, IL-17A-, and IL-22-induced CCL20 and antimicrobial peptide release from epidermal keratinocytes. Thus, our findings indicate that chrysin may have therapeutic potential against inflammatory skin diseases. Our study provides a basis for further investigating chrysin as a novel pharmacologic agent and contributes to the academic advancement in the field of Chinese herbal medicine.

The Inhibitory Effects of Gold Nanoparticles on VEGF-A-Induced Cell Migration in Choroid-Retina Endothelial Cells.

BACKGROUND: Vascular endothelial growth factor (VEGF) is upregulated by hypoxia and is a crucial stimulator for choroidal neovascularization (CNV) in age-related macular degeneration and pathologic myopia, as well as retinal neovascularization in proliferative diabetic retinopathy. Retinal and choroidal endothelial cells play key roles in the development of retinal and CNV, and subsequent fibrosis. At present, the effects of gold nanoparticles (AuNPs) on the VEGF-induced choroid-retina endothelial (RF/6A) cells are still unknown. In our study, we investigated the effects of AuNPs on RF/6A cell viabilities and cell adhesion to fibronectin, a major ECM protein of fibrovascular membrane. Furthermore, the inhibitory effects of AuNPs on RF/6A cell migration induced by VEGF and its signaling were studied. METHODS: The cell viability assay was used to determine the viability of cells treated with AuNPs. The migration of RF/6A cells was assessed by the Transwell migration assay. The cell adhesion to fibronectin was examined by an adhesion assay. The VEGF-induced signaling pathways were determined by western blotting. RESULTS: The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay revealed no cytotoxicity of AuNPs on RF/6A cells. AuNPs inhibited VEGF-induced RF/6A cell migration in a concentration-dependent manner but showed no significant effects on RF/6A cell adhesion to fibronectin. Inhibitory effects of AuNPs on VEGF-induced Akt/eNOS were found. CONCLUSIONS: These results suggest that AuNPs are an effective inhibitor of VEGF-induced RF/6A cell migration through the Akt/eNOS pathways, but they have no effects on their cell viabilities and cell adhesion to fibronectin.

Electronic cigarette exposure reduces exercise performance and changes the biochemical profile of female mice.

Electronic cigarette(s) (EC) becoming a preferred replacement for nicotine delivery among many smokers in recent years. However, the effect of EC on human health is inconclusive due to a lack of empirical research investigating EC-induced health hazard or benefit. In this study, we examine the effect of vapor produced by EC on exercise performance and health-related profiles in a mouse model. Female ICR mice were divided into five groups (n = 6 per group) and exposed for 14 days. Our results indicate that EC exposure leads to dose-dependent decrease in the grip strength and swimming time of the mice. The EC-treated groups also showed a dose-dependent decrease in liver and muscle glycogen storage. In addition, EC treatment had no negative effect on levels of biochemical indices. We also did not detect any adverse effect or gross abnormalities on the morphology of the major organs.

The effects of Jilin sika Deer's (Cervus dybowski) tendon liquid supplementation on endurance drop jumps performance, biochemistry profile of free boxing players.

ETHNOPHARMACOLOGICAL RELEVANCE: Risk of anterior cruciate ligament is a persistent and severe problem in athletes owing to strenuous exercise-induced lower-body injury. Tendon of deer liquid (TD) a familiar traditional Chinese medicine, has been used for strengthening the bones and muscles. AIM OF THE STUDY: In this study, we seek to demonstrate the application of TD in improving endurance exercise performance and reducing the risk of endurance training injury for free boxing players. MATERIALS AND METHODS: Sixteen male free boxing players were randomly assigned to the TD and placebo groups. Body composition, clinical biochemistry profiles, kinematic and physiology exercise tests were evaluated at 2 time points - pre-supplementation (pre-) and after 6 weeks post-supplementation (post-). RESULTS: TD group exhibited significant increase in levels of serum total protein (TP) compared to the placebo group after a 6-week supplementation. Following the treadmill test, serum glucose and maximal oxygen consumption (VO2 max) levels were increased in the TD group. In the endurance test consisting of 200 counts of drop vertical jumps (DVJs), subjects in the TD group also showed an increase in vertical jump height and reduced risk of musculoskeletal system injuries. CONCLUSIONS: TD supplementation leads to better physiological adaptation in free boxing players and has the potential for use as a nutrient supplement toward a variety of benefits for endurance athletes.

Laser ablation and topical drug delivery: a review of recent advances.

Introduction: The ablative laser can be used as an effective approach for enhancing drug permeation via the skin. The enhancement mechanisms of laser-assisted drug permeation are the direct ablation of the superficial skin, optical breakdown by a photomechanical wave, and a photothermal effect. Areas covered: This review describes the development of laser-assisted drug delivery in the recent 5 years. This review systematically introduces the concepts and enhancement mechanisms of the technique, highlighting the potential of the laser approach for increasing drug absorption via the skin. A recent advance of this approach is the use of fractional laser offering limited skin damage and short recovery time. Another sign of progress regarding laser-assisted drug delivery in the recent 5 years is the clinical trials for treating various dermatological disorders. Expert opinion: The potential use of the laser-assisted approach affords a novel treatment for topical drug application with significant efficacy. Although many clinical studies have been performed, further studies using a large group for patients are needed to confirm and clarify the findings in the in vitro or animal experiments. The laser-assisted delivery should be optimized to achieve skin targeting without the risk of diffusion into circulation.

Nanobubbles Water Curcumin Extract Reduces Injury Risks on Drop Jumps in Women: A Pilot Study.

PURPOSE: To verify the beneficial effects of Nanobubbles water curcumin extract (NCE) supplementation on health promotion and to demonstrate the application of NCE in reducing the risk of musculoskeletal injury. METHODS: In the current study, 12 females were randomly assigned to NCE (15g/day) and maltodextrin groups. Performance and related body composition were evaluated at 2 time points-presupplementation (pre-) and after 4 weeks of postsupplementation (post-). The posttest consists of a set of biochemical parameters for antifatigue activity and injury status evaluation. RESULTS: NCE group exhibited significantly lower levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), triglycerides (TG), and higher high-density lipoprotein (HDL) after a 4-week supplementation, compared with the placebo group. After a 15-minute session on the spinning bike, serum lactate and ammonia levels were decreased and glucose was economized in the NEC group. 4-week-NCE supplementation was also able to reduce the peak vertical ground reaction force (PVGRF) during drop jump. Therefore, the risk of musculoskeletal system in lower extremity could be reduced. CONCLUSION: We demonstrate that 4-week-NCE supplementation can also be used in explosiveness exercise for better physiological adaptation. Thus, NCE has potential for use with nutrient supplements toward a variety of benefits for athletics.

Post-irradiation recovery time strongly influences fractional laser-facilitated skin absorption.

Fractional CO2 laser treatment has been used in some clinical trials to promote topical drug delivery. Currently, there is no standard for laser settings to achieve a feasible therapy. The cutaneous recovery following laser treatment and its influence on drug absorption have not been well explored. This study evaluated the kinetics of laser-treated skin-barrier restoration and drug permeation in nude mice. The skin recovery and observation of the process were characterized by transdermal water loss (TEWL), erythema measurement, gross appearance, optical microscopy, and scanning electron microscopy (SEM). The skin absorption of a lipophilic small permeant (tretinoin), a hydrophilic small permeant (acyclovir), and a large molecule (fluorescein isothiocyanate dextran 4 kDa, FD4) was examined in vitro using Franz cell. TEWL suggested that the laser-treated skin restored its barrier function at 16 h after irradiation. The fractional laser produced microchannels of about 150 µm in diameter and 25 µm in depth that were surrounded with thermal coagulation. The bright-field imaging indicated that the micropores were progressively closed during the recovery period but had not completely closed even after a 16-h recovery. The laser treatment led to a rapid tretinoin penetration across the skin immediately after irradiation, with a 5-fold enhancement compared to intact skin. This enhancement was gradually reduced following the increase of recovery time. Conversely, the acyclovir and FD4 permeation peaked at 1-2 h post-irradiation. The FD4 flux was even elevated as the recovery time increased. The reasons for this could have been the subsequent inflammation after laser exposure and the deficient tight junction (TJ) barrier. The confocal imaging demonstrated the perpendicular diffusion of rhodamine B and FD4 through microchannels immediately after laser exposure. The lateral diffusion from the microchannels was observed at 2 h post-irradiation. Our results revealed a time-dependent recovery of skin permeation. The time frame for applying the drugs after laser irradiation was dependent upon the permeants and their various physicochemical properties.

Ludwigia octovalvis (Jacq.) raven extract supplementation enhances muscle glycogen content and endurance exercise performance in mice.

Ludwigia octovalvis extract (LOE) is a widely used traditional Chinese herbal medicine. To date, few studies have demonstrated the effect of LOE supplementation on exercise performance, physical fatigue and biochemical profile. The purpose of this study is to evaluate the potential beneficial effects of LOE extract on fatigue and ergogenic functions following physiological challenge. Male ICR mice from 3 groups (n=8 per group) were orally administered LOE for 4 weeks at 0 (vehicle), 61.5 (LOE-1X) or 307.5 (LOE-5X) mg/kg/day. LOE supplementation was able to dose-dependently increase endurance swimming time (P<0.0001) and decrease levels of serum lactate (P=0.0022), ammonia (P<0.0001), creatine kinase (P<0.0001), blood urea nitrogen (P<0.0001) and glucose utilization (P<0.0001) after acute exercise challenge. The glycogen in gastrocnemius muscle also increased with LOE treatment in a dose-dependent manner (P<0.0001). Biochemically, AST, ALT, LDH, CK, BUN, creatinine and UA levels were decreased with LOE treatment. Our study shows that 4-week supplementation with LOE increases muscle glycogen content storage to enhance exercise performance and anti-fatigue effects.

Spilanthol inhibits TNF­α­induced ICAM­1 expression and pro­inflammatory responses by inducing heme oxygenase­1 expression and suppressing pJNK in HaCaT keratinocytes.

Spilanthol has been reported to possess antioxidant, anti­inflammatory, antimicrobial and antinociceptive properties. At present, the literature has reported the beneficial role of spilanthol on tumor necrosis factor­α (TNF­α)­stimulated HaCaT cells. The present study investigated the effects of spilanthol on the expression of TNF­α­induced intercellular adhesion molecule 1 (ICAM­1) and cyclooxygenase (COX)­2 in the human keratinocyte cell line HaCaT. Cells were pretreated with various concentrations of spilanthol (10­150 µM) followed by TNF­α to induce inflammation. Pretreatment with spilanthol decreased TNF­α­induced COX­2 expression by western blotting and suppressed the expression of pro­inflammatory mediators, including interleukin (IL)­6, IL­8 and monocyte chemotactic protein 1 using ELISA. Spilanthol also decreased the expression of TNF­α­induced ICAM­1 protein and mRNA assay by western blotting and RT­qPCR, respectively, in addition to the monocyte adhesiveness of HaCaT cells. Furthermore, spilanthol significantly suppressed the phosphorylation of c­Jun N­terminal kinase (JNK), while pretreatment with spilanthol enhanced heme oxygenase (HO)­1 protein expression by western blotting. These results demonstrated that spilanthol may exert its anti­inflammatory activity by suppressing the TNF­α­induced expression of ICAM­1, COX­2 and pro­inflammatory mediators by enhancing that of HO­1, and inhibiting the activation of the phosphorylated JNK signaling pathway. It is hypothesized that spilanthol may be a natural anti­inflammatory drug to attenuate skin inflammatory disease.