Low Molecular Weight Collagen Peptide (LMWCP) Promotes Hair Growth by Activating the Wnt/GSK-3ß/ß-Catenin Signaling Pathway.

Low molecular weight collagen peptide (LMWCP) is a collagen hydrolysate derived from fish. We investigated the effects of LMWCP on hair growth using human dermal papilla cells (hDPCs), human hair follicles (hHFs), patch assay, and telogenic C57BL/6 mice, while also examining the underlying mechanisms of its action. LMWCP promoted proliferation and mitochondrial potential, and the secretion of hair growth-related factors, such as EGF, HB-EGF, FGF-4, and FGF-6 in hDPCs. Patch assay showed that LMWCP increased the neogeneration of new HFs in a dose-dependent manner. This result correlated with an increase in the expression of dermal papilla (DP) signature genes such as, ALPL, SHH, FGF7, and BMP-2. LMWCP upregulated phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) and ß-catenin, and nuclear translocation of ß-catenin, and it increased the expression of Wnt3a, LEF1, VEGF, ALP, and ß-catenin. LMWCP promoted the growth of hHFs and increased the expression of ß-catenin and VEGF. Oral administration of LMWCP to mice significantly stimulated hair growth. The expression of Wnt3a, ß-catenin, PCNA, Cyclin D1, and VEGF was also elevated in the back skin of the mice. Furthermore, LMWCP increased the expression of cytokeratin and Keratin Type I and II. Collectively, these findings demonstrate that LMWCP has the potential to increase hair growth via activating the Wnt/ß-catenin signaling pathway.

In Vitro and In Vivo Bone-Forming Effect of a Low-Molecular-Weight Collagen Peptide.

This study reveals that low-molecular-weight collagen peptide (LMWCP) can stimulate the differentiation and the mineralization of MC3T3-E1 cells in vitro and attenuate the bone remodeling process in ovariectomized (OVX) Sprague-Dawley rats in vivo. Moreover, the assessed LMWCP increased the activity of alkaline phosphatase (ALP), synthesis of collagen, and mineralization in MC3T3-E1 cells. Additionally, mRNA levels of bone metabolism-related factors such as the collagen type I alpha 1 chain, osteocalcin (OCN), osterix, bone sialoprotein, and the Runt family-associated transcription factor 2 were increased in cells treated with 1,000 µg/ml of LMWCP. Furthermore, we demonstrated that critical bone morphometric parameters exhibited significant differences between the LMWCP (400 mg/kg)-receiving and vehicle-treated rat groups. Moreover, the expression of type I collagen and the activity of ALP were found to be higher in both the femur and lumbar vertebrae of OVX rats treated with LMWCP. Finally, the administration of LMWCP managed to alleviate osteogenic parameters such as the ALP activity and the levels of the bone alkaline phosphatase, the OCN, and the procollagen type 1 N-terminal propeptide in OVX rats. Thus, our findings suggest that LMWCP is a promising candidate for the development of food-based prevention strategies against osteoporosis.

Protective Effect of Ribes nigrum Extract against Blue Light-Induced Retinal Degeneration In Vitro and In Vivo.

Although blackcurrant has several health benefits, such as antioxidant and anti-inflammatory properties, its effects on the retina remain unclear. In this study, we investigated the efficacy of black currant extract (BCE) in an in vitro and in vivo model of dry age-related macular degeneration (AMD) induced by blue light. Dry macular degeneration is characterized by the abnormal accumulation of lipofuscin (e.g., N-retinylidene-N-retinylethanolamine, A2E) in the retina. Blue light (BL) significantly decreased the viability of A2E-laden human retinal pigment epithelial cells (ARPE-19). However, BCE treatment protected ARPE-19 cells from A2E and BL. A2E, which is oxidized by blue light, generates reactive oxygen species in RPE cells. Treatment with BCE significantly decreased (80.8%) reactive oxygen species levels induced by A2E and BL in a concentration-dependent manner. BCE inhibited A2E accumulation in ARPE-19 cells and significantly downregulated the expression of genes increased by A2E and BL in ARPE-19 cells. In vivo, oral administration of BCE (25-100 mg/kg) ameliorated ocular lesions of BL-induced retinal damage in a mouse model and rescued the thickness of the whole retina, photoreceptor segment layer, outer nuclear layer, and inner nuclear layer. The decrease in the number of nuclei in the outer nuclear layer induced by BL was also rescued by BCE. Additionally, BCE administration rescued (40.0%) the BL-induced reduction in the expression level of superoxide dismutase 1. Taken together, our results suggest that BCE may have preventive and therapeutic effects on dry AMD through its antioxidant activity and inhibition of lipofuscin accumulation in the retina.

Effect of a Topical Collagen Tripeptide on Antiaging and Inhibition of Glycation of the Skin: A Pilot Study.

The glycation process has been recognized as one of the critical parameters that accelerate signs of skin aging, especially in skin exposed to environment factors, such as ultraviolet radiation. Although previous studies showed the anti-inflammatory and antiaging properties of the hydrolyzed collagen tripeptide (CTP), its exact mechanism is not fully understood. Therefore, in this study, we sought to investigate the effect of a topical CTP on facial skin. Our group designed a 4 week prospective, single-arm study of 22 Asian women who applied topical CTP. We observed significant improvements in skin wrinkles, elasticity, and density with a reduction in skin accumulation of advanced glycated end products (AGEs) at week 4 without any adverse effects. The in vitro study revealed a preventive effect of the topical CTP on the accumulation of AGEs, denatured collagen production, and reactive oxygen species in dermal fibroblasts. Moreover, treatment with the CTP decreased induction of matrix metalloproteinases while increasing the collagen 1 level. These results suggest that the application of a topical CTP might improve clinical aging phenotypes via the inhibition of glycation and oxidative stress, leading to a delay in cellular aging.

Ground Moving Target Tracking Filter Considering Terrain and Kinematics.

This paper addresses ground target tracking (GTT) for airborne radar. Digital terrain elevation data (DTED) are widely used for GTT as prior information under the premise that ground targets are constrained on terrain. Existing works fuse DTED to a tracking filter in a way that adopts only the assumption that the position of the target is constrained on the terrain. However, by kinematics, it is natural that the velocity of the moving ground target is constrained as well. Furthermore, DTED provides neither continuous nor accurate measurement of terrain elevation. To overcome such limitations, we propose a novel soft terrain constraint and a constraint-aided particle filter. To resolve the difficulties in applying the DTED to the GTT, first, we reconstruct the ground-truth terrain elevation using a Gaussian process and treat DTED as a noisy observation of it. Then, terrain constraint is formulated as joint soft constraints of position and velocity. Finally, we derive a Soft Terrain Constrained Particle Filter (STC-PF) that propagates particles while approximately satisfying the terrain constraint in the prediction step. In the numerical simulations, STC-PF outperforms the Smoothly Constrained Kalman Filter (SCKF) in terms of tracking performance because SCKF can only incorporate hard constraints.

Low-Molecular-Weight Collagen Peptide Ameliorates Osteoarthritis Progression through Promoting Extracellular Matrix Synthesis by Chondrocytes in a Rabbit Anterior Cruciate Ligament Transection Model.

This study examined whether the oral administration of low-molecular-weight collagen peptide (LMCP) containing 3% Gly-Pro-Hyp with >15% tripeptide (Gly-X-Y) content could ameliorate osteoarthritis (OA) progression using a rabbit anterior cruciate ligament transection (ACLT) model of induced OA and chondrocytes isolated from a patient with OA. Oral LMCP administration (100 or 200 mg/kg/day) for 12 weeks ameliorated cartilage damage and reduced the loss of proteoglycan compared to the findings in the ACLT control group, resulting in dose-dependent (p < 0.05) improvements of the OARSI score in hematoxylin & eosin (H&E) and Safranin O staining. In microcomputed tomography analysis, LMCP also significantly (p < 0.05) suppressed the deterioration of the microstructure in tibial subchondral bone during OA progression. The elevation of IL-1ßand IL-6 concentrations in synovial fluid following OA induction was dose-dependently (p < 0.05) reduced by LMCP treatment. Furthermore, immunohistochemistry illustrated that LMCP significantly (p < 0.05) upregulated type II collagen and downregulated matrix metalloproteinase-13 in cartilage tissue. Consistent with the in vivo results, LMCP significantly (p < 0.05) increased the mRNA expression of COL2A1 and ACAN in chondrocytes isolated from a patient with OA regardless of the conditions for IL-1ßinduction. These findings suggest that LMCP has potential as a therapeutic treatment for OA that stimulates cartilage regeneration.

Oral Intake of Low-Molecular-Weight Collagen Peptide Improves Hydration, Elasticity, and Wrinkling in Human Skin: A Randomized, Double-Blind, Placebo-Controlled Study.

Collagen-peptide supplementation could be an effective remedy to improve hydration, elasticity, and wrinkling in human skin. The aim of this study was to conduct a double-blind, randomized, placebo-controlled trial to clinically evaluate the effect on human skin hydration, wrinkling, and elasticity of Low-molecular-weight Collagen peptide (LMWCP) with a tripetide (Gly-X-Y) content >15% including 3% Gly-Pro-Hyp. Individuals (n = 64) were randomly assigned to receive either placebo or 1000 mg of LMWCP once daily for 12 weeks. Parameters of skin hydration, wrinkling, and elasticity were assessed at baseline and after 6 weeks and 12 weeks. Compared with the placebo group, skin-hydration values were significantly higher in the LMWCP group after 6 weeks and 12 weeks. After 12 weeks in the LMWCP group, visual assessment score and three parameters of skin wrinkling were significantly improved compared with the placebo group. In case of skin elasticity, one parameter out of three was significantly improved in the LMWCP group from the baseline after 12 weeks, while, compared with the placebo group, two parameters out of three in the LMWCP group were higher with significance after 12 weeks. In terms of the safety of LMWCP, none of the subjects presented adverse symptoms related to the test material during the study period. These results suggest that LMWCP can be used as a health functional food ingredient to improve human skin hydration, elasticity, and wrinkling.

Inhibitory Effects of Boesenbergia pandurata on Age-Related Periodontal Inflammation and Alveolar Bone Loss in Fischer 344 Rats.

Periodontitis, an infective disease caused by oral pathogens and the intrinsic aging process, results in the destruction of periodontal tissues and the loss of alveolar bone. This study investigated whether Boesenbergia pandurata extract (BPE) standardized with panduratin A exerted anti-periodontitis effects, using an aging model representative of naturally occurring periodontitis. In aged rats, the oral administration of BPE (200 mg·kg-1·day-1) for 8 weeks significantly reduced the mRNA and protein expression of interleukin-1ß, nuclear factor-kappa B, matrix metalloproteinase (MMP)-2, and MMP-8 in gingival tissues (p < 0.01). In alveolar bone, histological analysis with staining and micro-computed tomography revealed the attenuation of alveolar bone resorption in the BPE-treated aged group, which led to a significant reduction in the mRNA and protein expression of nuclear factor of activated T-cells c1 (NFATc1), c-Fos, tartrate-resistant acid phosphatase, and cathepsin K (p < 0.01). BPE not only increased the expression of osteoblast differentiation markers, such as alkaline phosphate, and collagen type I (COL1A1), but also increased the ratio of osteoprotegerin to RANKL. Collectively, the results strongly suggested that BPE is a natural resource for the prevention or treatment of periodontal diseases.

Oral intake of Boesenbergia pandurata extract improves skin hydration, gloss, and wrinkling: A randomized, double-blind, and placebo-controlled study.

BACKGROUND: Photoaging is a severe skin damage that occurs as a result of exposure to external elements, primarily ultraviolet (UV) irradiation. Chronically, UV-irradiated skin exhibits the signs of sunburn and hyperpigmentation with the destruction of connective tissues. Previously, Boesenbergia pandurata (B. pandurata) and its active compound panduratin A showed antiphotoaging activities in vitro and in vivo. OBJECTIVE: The aim of this study was to investigate the clinical efficacy of B. pandurata intake on skin hydration, gloss, wrinkling, and elasticity. METHODS: A double-blind, placebo-controlled trial was conducted to clinically evaluate the effect of B. pandurata ethanol extract (BPE) containing 8% of panduratin A on human skin hydration, gloss, wrinkling, and elasticity. Ninety-two subjects were randomly assigned to receive tablets containing either BPE or placebo for 12 weeks. RESULTS: The test group had significantly increased skin hydration and gloss and decreased wrinkling compared to the placebo group at 12 weeks. There was no significant difference in skin elasticity between the two groups; however, the increment rate in the test group was higher than that in the placebo group at 12 weeks. None of the subjects developed adverse symptoms during the study period. CONCLUSION: These results suggest that BPE can be used as a nutraceutical or nutricosmetic material for improving human skin hydration, gloss, and wrinkling.

Macelignan attenuated allergic lung inflammation and airway hyper-responsiveness in murine experimental asthma.

AIMS: Macelignan isolated from Myristica fragrans Houtt. is widely used for spice and flavoring for foods, and has been reported to have anti-inflammatory activity. The aim of this study was to investigate the effects of macelignan on allergic lung inflammation with a murine model of experimental asthma. MAIN METHODS: Fungal protease mixed with chicken egg ovalbumin allergen was used as a challenge to induce murine experimental asthma. To determine its effects on allergy and inflammation, macelignan was administered orally during allergen challenge, and the symptoms of allergic asthma and its underlined mechanisms were examined. KEY FINDINGS: Treatment with macelignan attenuated eosinophilic airway inflammation and airway hyper-responsiveness. With the administration of macelignan, interleukin-4 (IL-4) producing cells, but not interferon-γ (IFN-γ) or IL-17 producing cells, were diminished in the lungs. Additionally, activation of the T helper type 2 (Th2) cell-specific master transcription factor, GATA3 was decreased with macelignan treatment. Finally, production of IL-4 but not IFN-γ or IL-17, by CD4(+) T cells was reduced with stimulation when combined with the administration of macelignan. SIGNIFICANCE: Our data show that macelignan has anti-inflammatory effects on Th2 cell-mediated allergic lung inflammation and could potentially provide a novel preventative and/or therapy for the treatment of allergic diseases.

Effects of Collagen Tripeptide Supplement on Photoaging and Epidermal Skin Barrier in UVB-exposed Hairless Mice.

Collagen tripeptide (CTP) is a functional food material with several biological effects such as improving dry skin and wound and bone fracture healing. This study focused on the anti-photoaging effects of CTP on a hairless mouse model. To evaluate the effects of CTP on UVB-induced skin wrinkle formation in vivo, the hairless mice were exposed to UVB radiation with oral administration of CTP for 14 weeks. Compared with the untreated UVB control group, mice treated with CTP showed significantly reduced wrinkle formation, skin thickening, and transepidermal water loss (TEWL). Skin hydration and hydroxyproline were increased in the CTP-treated group. Moreover, oral administration of CTP prevented UVB-induced MMP-3 and -13 activities as well as MMP-2 and -9 expressions. Oral administration of CTP increased skin elasticity and decreased abnormal elastic fiber formation. Erythema was also decreased in the CTP-treated group. Taken together, these results strongly suggest that CTP has potential as an anti-photoaging agent.

Isolated coccygeal tuberculosis.

Isolated tuberculosis of the coccyx is extremely rare. A 35-year-old man presented with a 3-month history of coccygeal and gluteal pain. Computed tomography and magnetic resonance imaging revealed osseous destruction and a large enhancing mass involving the coccyx with anterior and posterior extension. Pathologic examination of the surgical specimen revealed necrosis, chronic granulomatous inflammation, and multinucleated giant cells consistent with tuberculosis. This case highlights the importance of considering tuberculosis as a diagnosis even though unusual sites are involved.