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Hematopoietic stem cell (HSC) gene therapy has the potential to cure many genetic, malignant, and infectious diseases. We have shown in a nonhuman primate gene therapy and transplantation model that the CD34+CD90+ cell fraction was exclusively responsible for multilineage engraftment and hematopoietic reconstitution. In this study, we show the translational potential of this HSC-enriched CD34 subset for lentivirus-mediated gene therapy. Alternative HSC enrichment strategies include the purification of CD133+ cells or CD38low/– subsets of CD34+ cells from human blood products. We directly compared these strategies to the isolation of CD90+ cells using a good manufacturing practice (GMP) grade flow-sorting protocol with clinical applicability. We show that CD90+ cell selection results in about 30-fold fewer target cells in comparison to CD133+ or CD38low/– CD34+ hematopoietic stem and progenitor cell (HSPC) subsets without compromising the engraftment potential in vivo. Single-cell RNA sequencing confirmed nearly complete depletion of lineage-committed progenitor cells in CD90+ fractions compared to alternative selections. Importantly, lentiviral transduction efficiency in purified CD90+ cells resulted in up to 3-fold higher levels of engrafted gene-modified blood cells. These studies should have important implications for the manufacturing of patient-specific HSC gene therapy and gene-engineered cell products.

Exposure to UV radiation is the primary cause of skin photoaging. UV damage is a result of increases in MMPs activity and degradation of collagen, resulting in wrinkle formation. Although the antioxidant potential of Urtica species is well known, the protective effects of Urtica thunbergiana against UVB-irradiated photoaging have not been explored. To examine the anti-photoaging effects of Urtica thunbergiana leaf extract (UT), levels of intracellular ROS, MMPs, IL-6, procollagen type 1, and TGF-β1 were investigated in UVB-irradiated NHDFs. We also examined anti-wrinkle effects of UT by measuring physiological and histological skin changes in hairless mice. Our data showed that UVB exposure decreased the level of phosphorylated NFATc1. One active component of UT, chlorogenic acid (CGA), regulated NFATc1 dephosphorylation to a similar extent as tacrolimus, a calcineurin inhibitor. Our results suggest that UT and its active component, CGA, have the potential to prevent UVB-induced premature skin aging by regulating NFATc1.

Ultraviolet (UV) light exposure induces skin damage, which can result in elevated matrix metalloproteinase (MMP) and in the loss of Type 1 procollagen. Rosa damascena (RD) is well known for its aromatic flowers. This aesthetic has led it to be used in the cosmetic industry to provide fragrances. Additionally, RD has been used as an herbal remedy for pharmacological conditions; it has not, however, been tested for its effect on photoaged skin. In this study, we investigated whether treatment with 50% ethanol RD extract induces a protective effect on photoaging. We found that RD impacted MMP transcription by suppressing AP-1 activation. Simultaneously, RD reversed the UV-induced reduction in Type 1 procollagen and TGF-β1 expression by regulating Smads. Finally, we observed a reduction in wrinkle formation after RD treatment on photoaging-induced hairless mice. Together, our findings indicate that RD may act as an effective anti-aging treatment if consumed as functional food.

Background: Human skin undergoes distinct changes throughout the aging process, based on both intrinsic and extrinsic factors. In a process called photoaging, UVB irradiation leads to upregulation of matrix metalloproteinase-1, which then causes collagen degradation and premature aging. Mixtures of medicinal plants have traditionally been used as drugs in oriental medicine. Based on the previously reported antioxidant properties of Panax ginseng Meyer and Crataegus pinnatifida, we hypothesized that the mixture of P. ginseng Meyer and C. pinnatifida (GC) would have protective effects against skin aging. Methods: Anti-aging activity was examined both in human dermal fibroblasts under UVB irradiation by using Western blot analysis and in healthy human skin by examining noninvasive measurements. Results: In vitro studies showed that GC improved procollagen type I expression and diminished matrix metalloproteinase-1 secretion. Based on noninvasive measurements, skin roughness values, including total roughness (R1), maximum roughness (R2), smoothness depth and average roughness (R3), and global photodamage scores were improved by GC application. Moreover, GC ameliorated the high values of smoothness depth (R4), which means that GC reduced loss of skin moisture. Conclusion: These results suggest that GC can prevent aging by inhibiting wrinkle formation and increasing moisture in the human skin.

Background: During the aging process, skin shows visible changes, characterized by a loss of elasticity and the appearance of wrinkles due to reduced collagen production and decreased elasticity of elastin fibers. Panax ginseng Meyer has been used as a traditional medicine for various diseases due to its wide range of biological activities including skin protective effects. Ginsenosides are the main components responsible for the biological activities of ginseng. However, the protective activities of an enzymatic preparation of red ginseng against human skin aging have not been investigated. Methods: The efficacy of an enzyme-treated powder complex of red ginseng (BG11001) in preventing human skin aging was evaluated by oral administration to 78 randomized individuals. All patients were requested to take three daily capsules containing either 750 mg of BG11001 or a placebo vehicle for 24 wk; at the end of the testing period, skin roughness, elasticity, and skin water content were measured. Results: BG11001 significantly reduced the average roughness of eye wrinkles and the Global Photo Damage Score compared with the placebo, although there were no significant differences in arithmetic roughness average between the groups. In addition, gross elasticity and net elasticity values increased, and transepidermal water loss level decreased, indicating improved skin elasticity and moisture content. Conclusion: In conclusion, enzyme-treated red ginseng extract significantly improved eye wrinkle roughness, skin elasticity, and moisture content. Moreover, enzyme-treated red ginseng extract would be useful substance as a bio-health skin care product.

Premature stop codons in CACNA1A, which encodes the α1A subunit of neuronal P/Q-type (CaV2.1) Ca2+ channels, cause episodic ataxia type 2 (EA2). CACNA1A undergoes extensive alternative splicing, which contributes to the pharmacological and kinetic heterogeneity of CaV2.1-mediated Ca2+ currents. We identified three novel heterozygous stop codon mutations associated with EA2 in an alternately spliced exon (37A), which encodes part of an EF-hand motif required for Ca2+-dependent facilitation. One family had a C to G transversion (Y1854X). A dinucleotide deletion results in the same premature stop codon in a second family, and a further single nucleotide change leads to a different truncation (R1858X) in a de novo case of EA2. Expression studies of the Y1854X mutation revealed loss of CaV2.1-mediated current. Because these mutations do not affect the alternate exon 37B, these findings reveal unexpected dependence of cerebellar function on intact exon 37A-containing CaV2.1 channels.