Skin Barrier-enhancing, Antiwrinkle, and Antimelanogenic Effects of Probiotic Lysates Composed of Nucleotides

Several previous studies have investigated the skin aging prevention effects of ceramide, hyaluronic acid, and natural or fermented plant materials. Recently, oral administration and dermal application of probiotics or probiotic lysates have shown antiaging effects. The purpose of this study is to optimize the preparation of probiotic lysates with a high concentration of nucleotides and to confirm the effects of probiotic lysates on the skin. Probiotic lysates were prepared by heating at 121°C for various periods with adding of sodium hyaluronic acid. Probiotic lysates of Bifidobacterium longum HDB7072, Lactobacillus paracasei HDB1196, and Lactobacillus acidophilus HDB1014 were applied to normal human epidermal keratinocytes (NHEKs), fibroblast cells, and B16F1 cells, respectively. Cell viability, antioxidant effects, and mRNA expression were evaluated by using MTT assays, DPPH assays, and qRT-PCR. Probiotic lysates prepared by heating the culture medium at 121°C for 2 h with 0.5% sodium hyaluronic acid showed the highest nucleotide concentration. In the three tested skin cells, the cell viability of filtered lysates was similar or higher to that of unfiltered lysates. HDB7072 lysates increased filaggrin expression in NHEKs. HDB1196 lysates showed DPPH radical-scavenging and antiwrinkle effects through the downregulation of matrix metalloproteinase-1 and upregulation of collagen type 1 in fibroblasts. HDB1014 lysates had antioxidant and antimelanogenic effects in B16F1 cells. Cell wall-removed probiotic lysates could be used as novel ingredients to improve skin aging and skin barrier issues.

Molecular docking of lutein as anti-photoaging agent in silico

The accumulation of UV exposure resulted in the loss of skin elasticity, and the appearance of wrinkles on the skin is commonly known as photoaging. Matrix metalloproteinase-1 (MMP-1) is an enzyme that degrades type I and III fibrillar collagen. This study aims to determine the mechanism of MMP-1 inhibition by lutein, a carotenoid compound with high antioxidant activity, using in silico molecular docking. This study was conducted by optimization of lutein structure using HyperChem 8, preparation of MMP-1 (PDB ID: 966C) using Chimera 1.10.1, validation of the method, and docking lutein against MMP-1 using Autodock 4.2. The results showed lutein had binding energy of -12.28 kcal/mol, lower than RS2 native ligand (-10.83 kcal/mol). The hydrogen bond formed between lutein and MMP-1 through HIS228 residue. To conclude, lutein may be developed as an anti-photoaging agent by inhibiting the MMP-1.

Anti-aging Effect of Mixed Extract from Medicinal Herbs

Purpose: This study was conducted to confirm the applicability of a mixed herbal extract (MHE) as an anti-aging cosmetic ingredient by investigating its skin anti-aging activities in vitro and in vivo.Methods: In this study, we prepared MHE using an ultrasonic extraction containing Forsythiae fructus, Tribuli fructus, Solomon’s seal, Siberian ginseng, Ponciri fructus and Ginseng. We investigated the anti-aging effect of the MHE for skin in dermal fibroblasts. The anti-aging activity was determined by the type I collagen synthesis levels. Matrix metalloproteinase-1 (MMP1) and tissue inhibitor of metalloproteinases 1 (TIMP1) mRNA levels were measured by qRT-PCR. MMP1 protein levels were evaluated by blotting analysis. Clinical tests of skin moisture, elasticity, texture, and wrinkles were performed using cosmetics containing 1% MHE.Results: The MHE induced the upregulation of pro-collagen type I synthesis and TIMP1 mRNA expression. The MHE led to the downregulation of MMP1 mRNA levels and protein levels. Furthermore, after skin application of cosmetics containing 1% MHE, skin hydration, elasticity, texture, and crow’s feet were improved 4 weeks after the treatment.Conclusion: MHE has an anti-aging effect by promoting collagen synthesis and suppressing MMP1 gene expression in vitro, and it has a skin improvement effect in vivo. Therefore, the MHE was shown to have value as a functional cosmetic ingredient.

Oral Cancer Theranostic Application of FeAu Bimetallic Nanoparticles Conjugated with MMP-1 Antibody

Metastatic oral squamous cell carcinoma (SCC) displays a poor disease prognosis with a 5-year survival rate of 39%. Chemotherapy has emerged as the mainstream treatment against small clusters of cancer cells but poses more risks than benefits for metastatic cells due to the non-specificity and cytotoxicity. To overcome these obstacles, we conjugated antibodies specific for matrix metalloproteinase-1 (MMP-1), a prognostic biomarker of SCC, to iron–gold bimetallic nanoparticles (FeAu NPs) and explored the capability of this complex to target and limit SSC cell growth via magnetic field-induced hyperthermia. Our results showed that 4.32 ± 0.79 nm sized FeAu NPs were superparamagnetic in nature with a saturation magnetization (Ms) of 5.8 emu/g and elevated the media temperature to 45 °C, confirming the prospect to deliver hyperthermia. Furthermore, conjugation with MMP-1 antibodies resulted in a 3.07-fold higher uptake in HSC-3 (human tongue squamous cell carcinoma) cells as compared to L929 (fibroblast) cells, which translated to a 5-fold decrease in cell viability, confirming SCC targeting. Finally, upon magnetic stimulation, MMP-1-FeAu NPs conjugate triggered 89% HSC-3 cellular death, confirming the efficacy of antibody-conjugated nanoparticles in limiting SCC growth. The synergistic effect of biomarker-specific antibodies and magnetic nanoparticle-induced hyperthermia may open new doors towards SCC targeting for improved disease prognosis.

Establishment of an Ex Vivo Inflammatory Osteoarthritis Model With Human Osteochondral Explants

Osteoarthritis (OA) is the most common degenerative joint disease without clear pathophysiological mechanism and effective drugs for treatment. Although various animal models exist, the translation of the outcome into clinics remains difficult due to species differences. In this study, an ex vivo inflammatory OA model was induced using different concentrations of interleukin one beta (IL-1β) and tumor necrosis factor α (TNF-α) on explants from the human femoral head. In the inflammatory OA groups, the gene expression levels of cartilage catabolism (matrix metalloproteinase 1 (MMP1), matrix metalloproteinase 3 (MMP3)), and inflammation (interleukin 6 (IL-6), interleukin 8 (IL-8)) markers were significantly upregulated, while the anabolic genes (collagen 2 (COL2), aggrecan (ACAN), and proteoglycan 4 (PRG4)) were downregulated compared to the control group. The release of cytokines (IL-6, IL-8) and nitric oxide (NO) in the conditioned medium was also upregulated in inflammatory OA groups. The Safranin O/Fast Green staining showed loss of proteoglycan in the superficial zone cartilage after cytokine treatment. The results indicated that an ex vivo inflammation and degeneration model was successfully established using osteochondral explants from the human femoral head. This model can be used to elucidate the in-depth mechanism of inflammatory OA and to screen new drugs for OA treatment.

Drosophila hemocytes recognize lymph gland tumors of mxc mutants and activate the Toll pathway in reactive oxygen species-dependent manner

Mechanisms of cancer cell recognition and elimination by the innate immune system remains unclear. Circulating hemocytes are associated with the hematopoietic tumors in Drosophila mxcmbn1 mutant larvae. The innate immune signalling pathways are activated in the fat body to suppress the tumor growth by inducing antimicrobial peptides (AMP). Here, we investigated the regulatory mechanism underlying the activation in the mutant. Reactive oxygen species accumulated in the hemocytes due to induction of dual oxidase and its activator. The hemocytes were also localized on the fat body. These were essential for transmitting the information on tumors toward the fat body to induce AMP expression. Regarding to the tumor recognition, we found that matrix metalloproteinase 1 (MMP1) and MMP2 were highly expressed in the tumors. Ectopic expression of MMP2 was associated with AMP induction in the mutants. Furthermore, the basement membrane components in the tumors were reduced and ultimately lost. The hemocytes may recognize the disassembly in the tumors. Our findings highlight the underlying mechanism via which macrophage-like hemocytes recognize tumor cells and relay the information toward the fat body to induce AMPs. and contribute to uncover the immune system's roles against cancer.

Spectral, Anti-Inflammatory, Anti-Pyretic, Leishmanicidal, and Molecular Docking Studies, Against Selected Protein Targets, of a New Bisbenzylisoquinoline Alkaloid

A new bisbenzylisoquinoline named as chondrofolinol (1) and four reported compounds (2–5) were isolated and characterized from the roots of Berberis glaucocarpa Stapf. Anti-inflammatory, anti-pyretic, and leishmanicidal studies were performed against carrageenan-induced paw edema, yeast-induced pyrexia, and the promastigotes of Leishmania tropica, respectively. The new compound significantly reduced the paw volume in carrageenan-induced paw edema and rectal temperature in yeast-induced pyrexia at 10 and 20 mg/ kg of body weight. Chondrofolinol caused almost 100% inhibition of the promastigotes of Leishmania tropica. All the compounds displayed minimal cytotoxicity against THP-1 monocytic cells. In order to ascertain the potential macromolecular targets of chondrofolinol responsible for the observed anti-inflammatory and anti-leishmanial activities, a molecular docking study was carried out on relevant protein targets of inflammation and Leishmania. Protein targets of human endoplasmic reticulum aminopeptidase 2 (ERAP2) and human matrix metalloproteinase-1 (MMP-1) for inflammation and protein targets of N-myristoyltransferase (NMT), tyrosyl-tRNA synthetase (TyrRS), and uridine diphosphate-glucose pyrophosphorylase (UGPase) for Leishmania major were selected after thorough literature search about protein targets responsible for inflammation and Leishmania major. Chondrofolinol showed excellent docking to ERAP2 and to MMP-1. The Leishmania major protein targets with the most favorable docking scores to chondrofolinol were NMT, TyrRS, and UGPase. The study indicated that bisbenzylisoquinoline and isoquinoline alkaloids possess anti-pyretic, anti-inflammatory, and anti-leishmanial properties with minimal cytotoxicity and therefore, need to be further explored for their therapeutic potential.