'Speed-ageing' of human skin in serum-free organ culture ex vivo: An instructive novel assay for preclinical human skin ageing research demonstrates senolytic effects of caffeine and 2,5-dimethylpyrazine.

Preclinical human skin ageing research has been limited by the paucity of instructive and clinically relevant models. In this pilot study, we report that healthy human skin of different age groups undergoes extremely accelerated ageing within only 3 days, if organ-cultured in a defined serum-free medium. Quantitative (immuno-)histomorphometry documented this unexpected ex vivo phenotype on the basis of ageing-associated biomarkers: the epidermis showed significantly reduced rete ridges and keratinocyte proliferation, sirtuin-1, MTCO1 and collagen 17a1 protein levels; this contrasted with significantly increased expression of the DNA-damage marker, γH2A.X. In the dermis, collagen 1 and 3 and hyaluronic acid content were significantly reduced compared to Day 0 skin. qRT-PCR of whole skin RNA extracts also showed up-regulated mRNA levels of several (inflamm-) ageing biomarkers (MMP-1, -2, -3, -9; IL6, IL8, CXCL10 and CDKN1). Caffeine, a methylxanthine with recognized anti-ageing properties, counteracted the dermal collagen 1 and 3 reduction, the epidermal accumulation of γH2A.X, and the up-regulation of CXCL10, IL6, IL8, MMP2 and CDKN1. Finally, we present novel anti-ageing effects of topical 2,5-dimethylpyrazine, a natural pheromone TRPM5 ion channel activator. Thus, this instructive, clinically relevant "speed-ageing" assay provides a simple, but powerful new research tool for dissecting skin ageing and rejuvenation, and is well-suited to identify novel anti-ageing actives directly in the human target organ.

Hesperetin activates CISD2 to attenuate senescence in human keratinocytes from an older person and rejuvenates naturally aged skin in mice.

BACKGROUND: CDGSH iron-sulfur domain-containing protein 2 (CISD2), a pro-longevity gene, mediates healthspan in mammals. CISD2 is down-regulated during aging. Furthermore, a persistently high level of CISD2 promotes longevity and ameliorates an age-related skin phenotype in transgenic mice. Here we translate the genetic evidence into a pharmaceutical application using a potent CISD2 activator, hesperetin, which enhances CISD2 expression in HEK001 human keratinocytes from an older person. We also treated naturally aged mice in order to study the activator's anti-aging efficacy. METHODS: We studied the biological effects of hesperetin on aging skin using, firstly, a cell-based platform, namely a HEK001 human keratinocyte cell line established from an older person. Secondly, we used a mouse model, namely old mice at 21-month old. In the latter case, we investigate the anti-aging efficacy of hesperetin on ultraviolet B (UVB)-induced photoaging and naturally aged skin. Furthermore, to identify the underlying mechanisms and potential biological pathways involved in this process we carried out transcriptomic analysis. Finally, CISD2 knockdown HEK001 keratinocytes and Cisd2 knockout mice were used to study the Cisd2-dependent effects of hesperetin on skin aging. RESULTS: Four findings are pinpointed. Firstly, in human skin, CISD2 is mainly expressed in proliferating keratinocytes from the epidermal basal layer and, furthermore, CISD2 is down-regulated in the sun-exposed epidermis. Secondly, in HEK001 human keratinocytes from an older person, hesperetin enhances mitochondrial function and protects against reactive oxygen species-induced oxidative stress via increased CISD2 expression; this enhancement is CISD2-dependent. Additionally, hesperetin alleviates UVB-induced damage and suppresses matrix metalloproteinase-1 expression, the latter being a major indicator of UVB-induced damage in keratinocytes. Thirdly, transcriptomic analysis revealed that hesperetin modulates a panel of differentially expressed genes that are associated with mitochondrial function, redox homeostasis, keratinocyte function, and inflammation in order to attenuate senescence. Intriguingly, hesperetin activates two known longevity-associated regulators, namely FOXO3a and FOXM1, in order to suppress the senescence-associated secretory phenotype. Finally, in mouse skin, hesperetin enhances CISD2 expression to ameliorate UVB-induced photoaging and this occurs via a mechanism involving CISD2. Most strikingly, late-life treatment with hesperetin started at 21-month old and lasting for 5 months, is able to retard skin aging and rejuvenate naturally aged skin in mice. CONCLUSIONS: Our results reveal that a pharmacological elevation of CISD2 expression at a late-life stage using hesperetin treatment is a feasible approach to effectively mitigating both intrinsic and extrinsic skin aging and that hesperetin could act as a functional food or as a skincare product for fighting skin aging.

Combined dasatinib and quercetin treatment contributes to skin rejuvenation through selective elimination of senescent cells in vitro and in vivo.

The skin's protective functions are compromised over time by both endogenous and exogenous aging. Senescence is well-documented in skin phenotypes, such as wrinkling and sagging, a consequence of the senescence-associated secretory phenotype (SASP) that involves the accumulation of senescent fibroblasts, chronic inflammation, and collagen remodeling. Although therapeutic approaches for eliminating senescent cells from the skin are available, their efficacy remains unclear. Accordingly, we aimed to examine the effects of dasatinib in combination with quercetin (D + Q) on senescent human skin fibroblasts and aging human skin. Senescence was induced in human dermal fibroblasts (HDFs) using approaches such as long-term passaging, ionizing radiation, and doxorubicin treatment. The generated senescent cells were treated with D + Q or vehicle. Additionally, a mouse-human chimera model was generated by subcutaneously transplanting whole-skin grafts of aged individuals onto nude mice. Mouse models were administered D + Q or vehicle by oral gavage for 30 days. Subsequently, skin samples were harvested and stained for senescence-associated beta-galactosidase. Senescence-associated markers were assessed by western blotting, reverse transcription-quantitative PCR and histological analyses. Herein, D + Q selectively eliminated senescent HDFs in all cellular models of induced senescence. Additionally, D + Q-treated aged human skin grafts exhibited increased collagen density and suppression of the SASP compared with control grafts. No adverse events were observed during the study period. Collectively, D + Q could ameliorate skin aging through selective elimination of senescent dermal fibroblasts and suppression of the SASP. Our findings suggest that D + Q could be developed as an effective therapeutic approach for combating skin aging.

Horizontal necklines correction with absorbable braided polydioxanone threads: Case series.

INTRODUCTION: The prevalence of horizontal neck lines as a cosmetic concern is widely acknowledged, yet the available treatment options are limited, and no studies have investigated the use of polydioxanone-barbed threads. These threads, characterized by a finely braided structure, function as a scaffold to attract regenerative factors and facilitate the migration and proliferation of cells. This study aims to evaluate the outcomes of concurrent application of braided polydioxanone-barbed threads for addressing horizontal neck wrinkles. METHODOLOGY: A retrospective case series involving four female participants (aged 41, 43, 45, and 46) treated with polydioxanone-barbed threads for horizontal neck wrinkles between January 2023 and July 2023 was conducted. Adult patients were assessed at an 8-week follow-up, revealing a significant reduction in wrinkle intensity based on the Horizontal Neck Wrinkle Severity Scale. RESULTS: The analysis of horizontal neck lines demonstrated a notable decrease in wrinkle intensity according to the Horizontal Neck Wrinkle Severity Scale at the 8-week mark, and this improvement maintained statistical significance. Both patient Global Aesthetic Improvement Scale (GAIS) scores (90%-100%) and physician GAIS scores (100%) were rated as excellent. CONCLUSION: The subdermal application of polydioxanone-barbed threads for horizontal neck lines proves to be a secure and efficacious approach for treating horizontal neck wrinkles, with no observed Tyndall effect. This technique shows promise for rejuvenating the skin in the horizontal neckline region.

Evaluation of a Novel Ablative 1940 nm Pulsed Laser for Skin Rejuvenation.

BACKGROUND: Skin rejuvenation is a widely sought-after goal, prompting advancements in laser technology for noninvasive and effective treatments. Ablative lasers, in particular, have evolved to address diverse skin concerns, with fractional ablative lasers offering better-tolerated outcomes. The introduction of a novel ablative Thulium pulsed laser, based on Thulium-doped Yttrium aluminum Perovskite (Tm:YAP) crystal, delivers precise and controlled skin rejuvenation by allowing customization of ablative microcolumns. METHODS: A pilot in vivo study was conducted on the abdominal skin of a live female pig. Using the Laser Team Medical (LTM) prototype laser, treatments were administered with varying coagulation settings (minimal and maximum) and energies (32, 80, 120, and 160 mJ per microcolumn). Biopsies were harvested, fixed, and stained for subsequent analysis. The penetration depth and width of the microcolumns were evaluated. RESULTS: Low coagulation settings produced ablative microcolumns with thermal affected zones of 160 µm width, while high coagulation settings resulted in wider zones of 400-530 µm. The ablation cavities' width was estimated to be less than 100 µm in both settings. The novel 1940 nm pulsed laser demonstrated superior microcolumn properties, offering potential advantages such as shorter downtime and increased efficacy compared to existing fractional ablative lasers. CONCLUSION: This study presents encouraging preliminary results regarding the efficacy and safety of the first ablative 1940 nm pulsed laser. The results show ablative microcolumns thinner than the counterpart devices, showing the device safety and potential higher efficacy along with short downtime. The LTM novel ablative 1940 nm pulsed laser holds immense potential for enhancing skin rejuvenation treatments due to its superior microcolumns properties. The versatility of this laser can open new treatment procedures and may extend to different areas of dermatology.

Extracellular Vesicles from Ecklonia cava and Phlorotannin Promote Rejuvenation in Aged Skin.

Plant-derived extracellular vesicles (EVs) elicit diverse biological effects, including promoting skin health. EVs isolated from Ecklonia cava (EV-EC) carry heat shock protein 70 (HSP70), which inhibits key regulators such as TNF-α, MAPKs, and NF-κB, consequently downregulating matrix metalloproteinases (MMPs). Aging exacerbates oxidative stress, upregulating MAPK and NF-κB signaling and worsening extracellular matrix degradation in the skin. E. cava-derived phlorotannin (PT) mitigates MAPK and NF-κB signaling. We evaluated the impact of EV-EC and PT on skin rejuvenation using an in vitro keratinocyte senescence model and an in vivo aged-mouse model. Western blotting confirmed the presence of HSP70 in EV-EC. Treatment with EV-EC and PT in senescent keratinocytes increased HSP70 expression and decreased the expression of TNF-α, MAPK, NF-κB, activator protein-1 (AP-1), and MMPs. Oxidative stress was also reduced. Sequential treatment with PT and EV-EC (PT/EV-EC) yielded more significant results compared to individual treatments. The administration of PT/EV-EC to the back skin of aged mice mirrored the in vitro findings, resulting in increased collagen fiber accumulation and improved elasticity in the aged skin. Therefore, PT/EV-EC holds promise in promoting skin rejuvenation by increasing HSP70 expression, decreasing the expression of MMPs, and reducing oxidative stress in aged skin.

Efficacy and safety of a home-use handheld multi-energy-based device for skin rejuvenation: clinical, ex vivo, and histological studies.

Alongside increases in the average lifespan and a growing interest in anti-aging remedies, the demand for at-home skincare devices is rapidly expanding in the cosmetic market. This study aimed to assess the safety and efficacy of a novel home-use handheld multi-energy-based device for skin rejuvenation that simultaneously emits low level light, low-dose radiofrequency, low-energy microcurrent, and low-intensity ultrasonic wave. This prospective, randomized, split-face clinical trial enrolled 36 healthy Korean women. After 8 weeks of device use, parameters associated with skin aging were assessed. Additionally, a preliminary ex vivo study and skin biopsy following device use were performed to confirm safety and efficiency of the device. Parameters associated with skin aging including skin hydration, elasticity, roughness, skin pore size, and eye wrinkle volume showed significant improvements after 8 weeks of the device use, relative to baseline measurements and the control side. No adverse effects were observed during the follow-up period. Results of ex vivo and in vivo skin tissue studies correlated with clinical findings, which showed an increase in the expression of type 1 collagen and a decrease in the expression of matrix metalloproteinase-1, which is related to the skin aging phenotype. The expression of loricrin and involucrin, major components of the epidermal skin barrier, also increased after the use of the device. Multi-energy-based device is effective for skin rejuvenation and tolerable, without any considerable adverse effects.

Enhancement of skin rejuvenation and hair growth through novel near-infrared light emitting diode (nNIR) lighting: in vitro and in vivo study.

The study aimed to explore the impact of a novel near-infrared LED (nNIR) with an extended spectrum on skin enhancement and hair growth. Various LED sources, including White and nNIRs, were compared across multiple parameters: cytotoxicity, adenosine triphosphate (ATP) synthesis, reactive oxygen species (ROS) reduction, skin thickness, collagen synthesis, collagenase expression, and hair follicle growth. Experiments were conducted on human skin cells and animal models. Cytotoxicity, ATP synthesis, and ROS reduction were evaluated in human skin cells exposed to nNIRs and Whites. LED irradiation effects were also studied on a UV-induced photoaging mouse model, analyzing skin thickness, collagen synthesis, and collagenase expression. Hair growth promotion was examined as well. Results revealed both White and nNIR were non-cytotoxic to human skin cells. nNIR enhanced ATP and collagen synthesis while reducing ROS levels, outperforming the commonly used 2chip LEDs. In the UV-induced photoaging mouse model, nNIR irradiation led to reduced skin thickness, increased collagen synthesis, and lowered collagenase expression. Additionally, nNIR irradiation stimulated hair growth, augmented skin thickness, and increased hair follicle count. In conclusion, the study highlighted positive effects of White and nNIR irradiation on skin and hair growth. However, nNIR exhibited superior outcomes compared to White. Its advancements in ATP content, collagen synthesis, collagenase inhibition, and hair growth promotion imply increased ATP synthesis activity. These findings underscore nNIR therapy's potential as an innovative and effective approach for enhancing skin and promoting hair growth.

Understand the Stabilization Engineering of Ascorbic Acid, Mapping the Scheme for Stabilization, and Advancement.

Vitamin C is extensively used in cosmetic formulation, howbeit stability is the supreme demerit that limits its use in beautifying products. Numerous techniques are being employed to inhibit the degradation of vitamin C caused by formulation components to facilitate the use in skin rejuvenating products. Diverse materials are being exercised in formulation to stabilize the ascorbic acid and ingredients selected in this formulation composition help for stabilization. The initial stable prototype is developed and further optimization is accomplished by applying the design of experiment tools. The stable pharmaceutical formulations were evaluated for the evaluation parameters and designated as two optimized formulations. The analytical method for the assay of ascorbic acid from the United States pharmacopeia and the related substance method from European pharmacopeia has been modified to be used for cream formulation. The DoE design exhibited that the stability of formulation is impacted by citric acid and tartaric acid but not by propylene glycol and glycerin. The analysis results of topical formulations for the evaluation parameter exhibited satisfactory results. The in-vitro release study method has been developed, optimized, and validated to fit the analysis. The in-vitro studies have been performed for selected compositions and both the formulation has similar kinds of release patterns. The stability study as per ICH guidelines exhibited that the product is stable for accelerated, intermediate, and room-temperature storage conditions. The optimized formulation shows constant release and permeation of ascorbic acid through the skin. The formulation with the combinations of citric acid, tartaric acid, and tocopherol is more stable and the degradation of vitamin C has been reduced significantly. The beaucoup strategies in the unique composition help to protect the degradation by inhibiting the multitudinous degradation pathways.

Effect of stem cell secretome in skin rejuvenation: a narrative review.

PURPOSE: Cutaneous aging is an inevitable biological process that develops over time due to cumulative cellular and molecular changes caused by exposure to intrinsic (chronological aging) and extrinsic (photo-aging) factors on the skin. Skin aging is characterized by a decline in the body's capability to sustain senescence, dermal cell apoptosis, and homeostasis. Stem cell secretions (secretome) are defined as the total set of dynamically overlapping paracrine soluble growth factors, cytokines, chemokines, angiogenic factors, extracellular matrix proteins, and antimicrobial peptides known to be responsible for tissue rejuvenation, regeneration, homeostasis, and immunomodulation. METHODS: In this review, we summarized the molecular and regulatory mechanism of the secretome in preventing the skin aging process, as well as its capacity in inducing skin rejuvenation. Furthermore, we illustrated secretome efficiency as an anti-aging therapeutic strategy based on in vitro and in vivo published studies. RESULTS: In all reviewed publications, the secretome has been proven to be the most effective treatment for aged skin, capable of reversing the aging process through the action of cytokines, growth factors, and collagen, which are its primary components. The reported mechanism of action involves modulating the signaling pathways of aging and replenishing the skin with collagen, fibronectin, and elastin, ultimately resulting in skin renewal and rejuvenation. CONCLUSION: In conclusion, compared to available treatments, the secretome shows great promise as an anti-aging therapy.

Efficacy of radiofrequency combined with single-dot ultrasound efficacy for skin rejuvenation: A non-randomized split-face trial with blinded response evaluation.

BACKGROUND: High-intensity focused ultrasound (HIFU) and radiofrequency (RF) are non-invasive modalities for skin rejuvenation, but their combined effects have not been evaluated. OBJECTIVE: We evaluated and compared the efficacy of HIFU alone and combined HIFU and bipolar RF using a newly designed probe. METHODS: Twenty-two Korean adults with facial wrinkles and aging underwent treatment on both sides of their face: HIFU-only on the left and HIFU combined with RF on the right. Skin parameters were measured at different time points to evaluate the improvement in skin rejuvenation. RESULTS: HIFU treatment significantly improved skin parameters, including pore volume and number, skin elasticity, depth of eye wrinkles, degree of sagging in the eye area, nasolabial folds and cheeks, volume of the jawline, skin density, and permittivity. Furthermore, combining bipolar RF with HIFU treatment enhanced efficacy in reducing pore number, improving skin elasticity, diminishing eye wrinkle depth, and increasing skin moisturization. These findings indicate that bipolar RF can synergically improve skin rejuvenation by providing a thermal effect to the upper papillary dermis, which is more superficial than the target area of HIFU. CONCLUSION: Combining HIFU with bipolar RF synergistically improves skin rejuvenation, including pore reduction, periorbital wrinkle improvement, skin elasticity, and skin moisturization.

Effect of geometric parameters of electrodes on skin heating for the design of non-ablative radiofrequency device.

BACKGROUND: Non-ablative radiofrequency (RF) has been widely used in clinical and at-home cosmetics devices. RF electrode geometry can influence the heat distribution in the tissue. This study analyzes the influence of geometric parameters of the electrode on the heat distribution in the layered tissue. MATERIALS & METHODS: The finite element simulation of the electrothermal coupling field was performed to obtain the three-dimensional (3D) temperature distribution of the four-layer tissue. The electrode geometric parameters including the inter-electrode spacing (5-12 mm), width (1-3 mm), length (3-10 mm), shapes (bar, dot and circle), and the coupling gel's electrical conductivity (0.2-1.5 S/m) were simulated. The maximum temperature at 2 mm depth (T-2 mm ) and the temperature difference (Tdiff ) between the maximum skin surface temperature and T-2 mm were obtained to evaluate the effectiveness and safety. RESULTS: The effect of geometric parameters on the effectiveness and safety was mixed. The maximum T-2 mm occurred with the 5 mm inter-electrode spacing, 3 mm width, 10 mm length, the circle-shaped electrode, and the 1.5 S/m coupling gel's electrical conductivity. The ratio of inter-electrode spacing to width at around four can achieve rapid temperature rise and skin surface temperature protection. The electrode shape influenced the area of temperature rise in the tissue's cross-section. The coupling gel's electrical conductivity should be close to that of the skin to avoid energy accumulation on the skin surface. CONCLUSION: The electrode's geometric parameters affect the effectiveness and safety of the RF product. This study has provided the simulation procedure for the electrode design.

Morphologic and molecular biologic analyses of the skin rejuvenation effect of the fractional 1064-nm picosecond laser: An animal study.

OBJECTIVES: Application of the picosecond laser in the field of dermatology has expanded from tattoo removal to skin rejuvenation on a clinical basis. Although various mechanisms of pigment removal have been elucidated, the molecular changes associated with skin rejuvenation have yet to be identified. The aim of this study was to explore the theoretical basis and to evaluate the efficacy of skin rejuvenation using a 1064-nm fractional picosecond laser in a mouse model. METHODS: We conducted an in vivo study using a fractional picosecond laser on the skin of old and young female hairless mice and performed topographical, histological, micro-, and electron microscopic assessments. RESULTS: The topography of the skin surface was enhanced and showed increased dermal thickness on histological examination. Electron microscopy revealed disarranged collagen bundles with microspaces and vascular leakage in the upper dermis. Levels of collagen synthesis markers and various inflammatory cytokines, such as procollagens, interleukin-1ß, tumor necrosis factor-α, and heat shock proteins, were elevated in the laser-treated skin. CONCLUSIONS: This study provides a possible mechanism for the skin rejuvenation effect of fractional picosecond laser that has been reported previously in clinical observations. Based on our findings, the fractional picosecond laser could be widely applied in clinical settings where dermal regeneration and promotion of skin rejuvenation is required.

Needleless laser injector versus needle injection for skin enhancement and rejuvenation effect of dermal filler.

BACKGROUND AND OBJECTIVES: A needleless laser-induced microjet injector is a novel transdermal drug delivery system that can rapidly inject a very small and precise drug dose into the skin with minimal pain and downtime. In this study, we aimed to compare the laser-induced microjet injection versus needle injection of polylactic acid/hyaluronic acid filler for skin enhancement and rejuvenation. PATIENTS AND METHODS: A 24-week prospective, single-center, assessor-blinded, randomized, split-face study was conducted. The enrolled patients underwent one treatment session of dermal filler injection using a laser-induced microjet injector on one half of the face or a traditional needle injection on the other half of the face. Evaluation was conducted at baseline before treatment and at 4, 12, and 24 weeks after treatment. RESULTS: A single treatment of filler injection with a laser-induced microjet injector resulted in similar improvements in skin hydration and elasticity as a single treatment of filler injection by using manual needle injection, with reduced pain, side effects, and decreased treatment time. CONCLUSIONS: Laser-induced microjet injector enabled not only the application of a controlled dose and filler depth but also even distribution, improved clinical efficacy, reduced pain and side effects, and sufficient time for clinicians to perform treatment.

Skin rejuvenating effect of a combined triple-wavelength (755 nm, 810 nm, and 1064 nm) laser: a preliminary study.

With an increasing demand for noninvasive skin rejuvenation techniques, several light-based devices have been introduced. Due to its ability to deliver thermal energy from the superficial to deeper levels of the dermis, a combined triple-wavelength laser (755 nm, 810 nm, and 1064 nm) can be used for skin rejuvenation. The objective of this study was to assess the effectiveness and safety of a combined triple-wavelength laser for skin rejuvenation. A total of 28 female patients seeking skin rejuvenation treatment were included. All patients underwent five consecutive treatment sessions at a two-week interval. Clinical improvement of aging-related cutaneous change was noted by the treating dermatologists and patients. Biopsies were performed on the faces of consenting patients before and two weeks after the final treatment. Significant clinical improvements were observed by both patients and evaluating dermatologists. Based on the patient satisfaction questionnaire, 78% of patients reported a self-assessed improvement of more than 25%. Additionally, 86% of patients showed an improvement of more than 25% on objective assessment by dermatologists. Histopathological findings revealed increased collagen and elastic bundles throughout the dermis. Except for transient pain during treatment, no serious adverse effects were reported. The findings of this study suggest that the combined triple-wavelength laser may be an effective and safe nonablative option for skin rejuvenation.

Efficacy of skin rejuvenation with a fractional 1927-nm thulium laser alone or combined with a chemical peel: a controlled histopathological preliminary study in a mouse model.

Many patients demand minimally invasive treatments for skin rejuvenation, such as nonablative laser and superficial chemical peels. Combination therapy yet has not been studied histopathologically. The purpose of this study is to assess the histopathological efficacy of a 1927-nm thulium laser-assisted salicylic acid (SA) peel in skin rejuvenation. A six-segment table was drawn on the shaved back of C57BL/6 mouse. All segments were irradiated with the thulium laser-different tips and passes were used for specific segments. A 30% SA peel was then applied to the right-hand segments. After treatment, the skin samples were collected from each segment and examined for dermal thickness, collagen density, and melanin content. Greater thickness was seen in the combination therapy group compared with the laser alone group and in those segments receiving more passes with larger beam-sized tip. Collagen density increased in all treated skin segments, irrespective of the group. No adverse events were noted in the treated areas. The sample size was small and mouse skin has histological differences with human skin. The combination of a thulium laser and 30% SA peel has a synergistic effect on dermal thickness, so that can be suggested as a novel skin rejuvenation technique.

Ginkgo biloba leaves extract's cosmeceutical evaluation: a preliminary assessments on human volunteers towards achieving improved skin condition and rejuvenation.

BACKGROUND: Ginkgo biloba (GB) leaves extract is known to possess potent antioxidants and other bioactivities such as improved skin conditions and rejuvenation. OBJECTIVE: This study aimed to develop a cosmeceutical preparation to utilize the strong antioxidant potential of GB leaves as part of the skincare formulation. METHODS: Cream incorporated GB (GBC) was prepared by mixing the obtained extract with stearic acid-sodium hydroxide components in an emulsion format. The obtained GBC was characterized for GB contents, uniformity, pH, compatibility, stability, and skin's human application. RESULTS: A homogeneous, physically, and chemically stable, with pH near the skin pH and shiny cream, was obtained. The prepared cream was easy to rub and pearly in appearance. It was effective and safe during the two-week trial conducted on human volunteers according to clinical trial registry protocols. The cream scavenged free radicals in DPPH assay tests. The cream incorporated GB made the skin more spirited and tauter. Furthermore, the wrinkles were reduced and the skin was renewed vigor. CONCLUSION: The GBC worked at the topical level and provided benefits when applied daily for the trial duration. The formulation also provided visually observable anti-wrinkle effects on the skin, with visible improvements in the skin's shape and texture. The prepared cream can be used to rejuvenate the skin.

Safety and Effectiveness of Endodermal Radiofrequency for Skin Rejuvenation: A Systematic Review.

BACKGROUND: With the advent of new technologies, the demand for non-invasive and effective procedures to treat skin laxity has increased. In this research, we aimed to review studies conducted on the safety and effectiveness of endodermal radiofrequency (ER) for skin rejuvenation. METHODS: We searched the databases of Embase, PubMed, Scopus, and Google Scholar from 2000 to 2020 to conduct a systematic review based on the PRISMA statement. Screening of titles, abstracts, and full-text articles was performed independently by two reviewers according to inclusion and exclusion criteria. RESULTS: This study showed that ER resulted in improvement in wrinkles and sagging, reduction of fat, tightening of skin of the face, neck, and jawline, improvement in skin elasticity, pigmentation, contouring of the body, and epidermal thickness decrease. ER technology leads to a significant and satisfactory improvement in skin rejuvenation, lower contouring of skin of the face and neck, as well as patients' satisfaction. Side effects of ER are temporary, and usually disappear spontaneously after a few days to one month. CONCLUSION: Cosmetic services providers can use this effective and safe technology to treat skin laxity and skin rejuvenation as a substitute for surgery. Level of evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Poly-D,L-Lactic Acid Stimulates Angiogenesis and Collagen Synthesis in Aged Animal Skin.

Angiogenesis promotes rejuvenation in multiple organs, including the skin. Heat shock protein 90 (HSP90), hypoxia-inducible factor-1 alpha (HIF-1α), and vascular endothelial growth factor (VEGF) are proangiogenic factors that stimulate the activities of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and extracellular signal-regulated kinase 1/2 (ERK1/2). Poly-D,L-lactic acid (PDLLA), polynucleotide (PN), and calcium hydroxyapatite (CaHA) are dermal fillers that stimulate the synthesis of dermal collagen. However, it is not yet known whether these compounds promote angiogenesis, which leads to skin rejuvenation. Here, we evaluated whether PDLLA, PN, and CaHA stimulate angiogenesis and skin rejuvenation using H2O2-treated senescent macrophages and endothelial cells as an in vitro model for skin aging, and we used young and aged C57BL/6 mice as an in vivo model. Angiogenesis was evaluated via endothelial cell migration length, proliferation, and tube formation after conditioned media (CM) from senescent macrophages was treated with PDLLA, PN, or CaHA. Western blot showed decreased expression levels of HSP90, HIF-1α, and VEGF in senescent macrophages, but higher expression levels of these factors were found after treatment with PDLLA, PN, or CaHA. In addition, after exposure to CM from senescent macrophages treated with PDLLA, PN, or CaHA, senescent endothelial cells expressed higher levels of VEGF receptor 2 (VEGFR2), PI3K, phosphorylated AKT (pAKT), and phosphorylated ERK1/2 (pERK1/2) and demonstrated greater capacities for cell migration, cell proliferation, and tube formation. Based on the levels of 4-hydroxy-2-nonenal, the oxidative stress level was lower in the skin of aged mice injected with PDLLA, PN, or CaHA, while the tumor growth factor (TGF)-ß1, TGF-ß2, and TGF-ß3 expression levels; the density of collagen fibers; and the skin elasticity were higher in the skin of aged mice injected with PDLLA, PN, or CaHA. These effects were greater in PDLLA than in PN or CaHA. In conclusion, our results are consistent with the hypothesis that PDLLA stimulates angiogenesis, leading to the rejuvenation of aged skin. Our study is the first to show that PDLLA, PN, or CaHA can result in angiogenesis in the aged skin, possibly by increasing the levels of HSP90, HIF-1α, and VEGF and increasing collagen synthesis.

Laser Impacts on Skin Rejuvenation: The Use of a Synergistic Emission of CO2 and 1540 nm Wavelengths.

Background and Objectives: For nearly 15 years, carbon dioxide (CO2) laser has been the gold standard in skin rejuvenation. Aim: The purpose of this study was to assess the efficacy of a new laser device which combines CO2 and 1540 nm wavelengths in wrinkles reduction, using a recently developed scanning unit named the µScan DOT scanner. Materials and Methods: A total of 20 female patients underwent from two to four laser treatment sessions performed once every 45-90 days. Wrinkles reduction was evaluated using the Fitzpatrick Wrinkle Classification System (FWCS). Evaluations of five-point Global Patient's Assessment (PGA) and an Oedema and Erythema index based on a four-point scale were carried out. A careful photographic evaluation was performed to observe the patients' aesthetic improvements. All the assessments were performed before and at 3 months follow up (3 MFU) after the last treatment session. Results: The mean FWCS score significantly (p < 0.01) decreased from 5.45 ± 2.21 at baseline to 3.3 ± 1.78 at 3 MFU after the last treatment session. In total, 8/20 (40%) subjects reported excellent improvement, 7/20 (35%) subjects showed good improvement, 5/20 (25%) subjects showed slight improvement, and 0/20 (0%) subjects showed no improvement. Concerning the Oedema index, 15/20 subjects experienced a mild one, 5/20 subjects experienced a moderate one, and none of 20 experienced a severe one, while for the Erythema index, 1/20 patients experienced mild, 18/20 patients experienced moderate, and only 1/20 patient experienced severe erythema. No severe adverse events were observed. Conclusions: This dual-wavelength laser technique may become a promising new option for safe, nonsurgical improvement for skin rejuvenation with an extremely low risk of scarring or hypopigmentation and shorter healing times.