Topical Application of Skin Biome Care Regimen Containing Live Cultures and Ferments of Cutibacterium acnes defendens strain XYCM42 and the Impact on Clinical Outcomes Following Microneedle-induced Skin Remodeling.

Background: The skin, our body's largest organ, hosts a complex microbiome that plays a pivotal role in maintaining health and protecting against pathogens. Even slight disruptions to this delicate balance can influence skin health and disease. Among the diverse microbial community, Cutibacterium acnes (C. acnes) subspecies defendens is known for its positive contribution to skin health. However, the interaction between living microbe probiotics and wound healing after aesthetic procedures, such as microneedling, remains unexplored. Methods: Our study included 40 participants with acne scars who underwent four microneedling sessions spaced three weeks apart. They were randomly assigned to Group 1, receiving a regimen with live C. acnes defendens strain XYCM42, or Group 2, following a conventional skincare routine with a cleanser, moisturizer, and sunscreen. Our study assessed various endpoints, including the Clinician's Global Aesthetic Improvement Scale (CGAIS), clinical safety, improvement in acne scars using Goodman and Baron's Qualitative and Quantitative Acne Scars Grading Scale and Subject's Global Aesthetic Improvement Scale (SGAIS). Results: Our analysis of live and photo grading data for CGAIS unveiled a statistically significant difference between the two groups, with Group 1 (XYCM42-based regimen) showing remarkable improvement. A similar positive trend was observed in the photo grading for CGAIS. Additionally, participant diaries indicated that Group 1 experienced a faster decline in posttreatment parameters, including erythema, swelling, burning/tingling, and itching. Conclusion: Integrating a microbiome-optimized, probiotic XYCM42-based regimen with microneedling demonstrated a high safety profile and enhanced treatment outcomes. These findings mark a milestone in aesthetic dermatology, supporting innovative microbiome-based approaches to improve skin health and aesthetics.

Study to determine the safety and efficacy of microneedling as an effective treatment for acne vulgaris.

Background: Acne is an inflammatory disease of the pilosebaceous unit that occurs primarily in adolescents. There is no current ideal treatment for acne vulgaris, as many mainstay prescription treatment modalities can compromise the skin microbiome or have deleterious health effects. Further research is needed to investigate novel treatment modalities that account for the importance of the skin microbiome. Other developing treatment modalities for acne are still taking a similar mode of action as current treatments by trying to eliminate Cutibacterium acnes despite growing evidence that some C. acnes strains may be symbiotic in nature. The perception that microneedling will exacerbate the disease state and trigger more acneic lesions via the spread of acne-associated microbes has hindered research investigating whether microneedling is a safe and effective treatment. This pilot clinical study challenges such perceptions by clinical assessment to determine if microneedling may produce beneficial treatment outcomes without disrupting critical skin structure or skin microbiome. Objectives: Test the safety and efficacy of microneedling as an effective treatment modality for acne vulgaris. Methods: Subjects were split into two groups, one group received three treatments 4 weeks apart, and the second group received four treatments 2 weeks apart. Subjects received an acne assessment by an expert clinical grader at all clinical visits. Results: There was a statistically significant reduction in both non-inflammatory and inflammatory lesions at the 2-month follow-up compared to the baseline for Group 1. Group 1 and Group 2 saw a decline of 48.20% and 54.00% in non-inflammatory lesions and 57.97% and 36.67% in inflammatory lesions, respectively, at their last visit compared to baseline. Conclusion: This study expands the utility of microneedling into a potential therapeutic modality for acne vulgaris. The data generated during the duration of this clinical study demonstrates that there is no scientific reason for microneedling to be contraindicated for acne. In this pilot, microneedling did not cause post-treatment complications and was seen to reduce acne lesions effectively. Thus, microneedling may have the potential to be a well-tolerated option for those suffering from acne, being a treatment that neither damages the sebaceous glands nor disrupts the skin microbiome.

Efficacy and tolerability of a microneedling device for treating wrinkles on the face.

OBJECTIVES: A microneedling pen has been cleared by the US Food and Drug Administration, indicated for improving the appearance of adult facial acne scars. The objective of this study was to assess the device's effectiveness for treating wrinkles of the face area. MATERIALS AND METHODS: Healthy adults seeking to improve the appearance of face wrinkles were enrolled (N = 35), receiving four monthly microneedling procedures by a trained aesthetician who treated the face skin per manufacturer instructions. Wrinkle assessments were performed by two trained blinded raters by comparing baseline images of each subject with images obtained at 90 days post-procedure. Subsequently, the two raters were unblinded for the Clinician's Global Aesthetic Improvement Scale (CGAIS) assessment. Subjects completed the Subject's Global Aesthetic Improvement Scale (SGAIS) and a Satisfaction Questionnaire at 30 and 90 days post-treatment. RESULTS: The study was completed by 32 subjects with a mean (SD) age of 56.3 (5.0) years. Wrinkle assessments demonstrated significant improvement in the face areas (p < 0.001). The SGAIS scores showed significant improvements after 30 and 90 days post-treatment (for each, p < 0.001). The CGAIS scores also showed significant improvements at 90 days post-treatment (p < 0.001). Most subjects reported some level of improvement in their appearance at 30 days (73.3%) and 90 days (68.8%) post-treatment. The satisfaction questionnaire showed high levels of improvement in wrinkles (93.8%), satisfaction with the treatment procedure (87.5%) and would recommend microneedling to friends and family members (80.6%) on the face and neck. CONCLUSION: Microneedling is a viable, minimally invasive option for treating wrinkles of the face. CLINICALTRIALS: gov Identifier: NCT03803059.

Characterization of a live Cutibacterium acnes subspecies defendens strain XYCM42 and clinical assessment as a topical regimen for general skin health and cosmesis.

BACKGROUND: When formulating topical products to treat skin diseases and addressing general skin health and cosmesis, most of the focus has traditionally been placed on how any given ingredient may impact the structure, function, and health of human skin elements. However, recent research is beginning to highlight the importance of the skin microbiome in relation to certain skin conditions and general cosmesis. Cutibacterium acnes is one of the most prolific skin-specific bacterial species. Research has shown that the species is divided into subspecies, some of which are thought to be beneficial to the skin. This paper aims to determine the efficacy of strainXYCM42, a C. acnes subspecies defendens derived strain designed to improve the health and appearance of the skin. METHODS: In vitro studies were performed on human keratinocyte and fibroblast monolayers, human peripheral blood mononuclear cells (PBMC), and skin explants to elucidate the effects of live XYCM42 cells and their ferment on human skin cells and tissues. Subsequently, clinical studies were performed using XYCM42-based topical regimens designed to deliver and support the engraftment of live XYCM42 cells onto subjects' skin. Two studies were performed, a 3-week pilot study (n = 10) and a 8-week pivotal study (n = 121). In the latter, 32 subjects were enrolled for an in-clinic portion for efficacy evaluation, with clinic visits occurring at Baseline, Week 1, Week 4, and Week 8. RESULTS: In vitro data suggest that XYCM42 and its ferment filtrate have potential to provide benefits to the skin via antioxidant, anti-inflammatory, and select antimicrobial activities. Clinical observation demonstrated that a XYCM42-containing regimen supports a healthy skin environment, promotes increased skin hydration, decreases erythema, calms the skin, and regulates sebum production. CONCLUSION: These studies provide further evidence that specific strains of C. acnes, such as XYCM42, have a more beneficial function regarding skin health and appearance than was previously thought. Appropriate use of formulations derived from symbiotic strains within the skin microbiome can support the development of novel, beneficial topicals.

Review of the safety profile for microfocused ultrasound with visualization.

The Safety of Microfocused Ultrasound with Visualization (MFU-V) has been well established in both controlled clinical studies and in clinical use, showing only mild and transient anticipated side effects and only rare unanticipated adverse events (AEs). This publication discusses the safety profile of MFU-V based on data from a variety of sources. Reports of side effects and AEs were obtained from published peer-reviewed medical literature, clinical studies, in-market use reports (AEs reported to the manufacturer), and retrospective chart reviews of patient treatments. Events that were typical included tenderness, redness, and slight edema. Rare events included bruising, welting, and nerve-related effects (paresthesia and paresis). Rare incidence of surface thermal effects was seen in some cases where improper technique was used. In all cases where the device was uses properly, the safety events reported tended to be transient, mild in nature, and resolved without sequelae. In general, unexpected and rare AEs could be attributed to incorrect treatment technique or classified as unrelated to MFU-V treatment. Side effects that do occur are generally mild and transient in nature. MFU-V consistently allows for safe treatment when correct treatment technique is used.

Involvement of thioredoxin domain-containing 5 in resistance to nitrosative stress.

Living organisms are exposed to nitrosative stress mediated by nitric oxide (NO) and its derivatives. Multiple cellular mechanisms may be needed to cope with nitrosative stress. This work takes advantage of a hypersensitive Escherichia coli genetic system to identify genes involved in resistance to nitrosative stress in mouse lungs. Mouse thioredoxin domain-containing 5 (mTrx 5) was identified as one of the candidate genes. Its ability to complement the hypersensitive phenotype in an E. coli mutant strain was confirmed by genetic analysis. Purified recombinant mouse thioredoxin domain-containing 5 protein reduced DNA damage that is sensitive to cleavage by the deamination repair enzyme endonuclease V, indicating that mTrx 5 may play a role in scavenging the reactive nitrogen species. E. coli thioredoxin 1 and thioredoxin 2 proteins also reduced the DNA damage in a similar manner. Deletion of trxA (encodes thioredoxin 1) or trxC (encodes thioredoxin 2) in E. coli resulted in a slightly higher sensitivity to nitrosative stress. On the other hand, deletion of both trxA and trxC greatly increased its sensitivity to nitrosative stress. Complementation with the mTrx 5 gene rescued the sensitive phenotype of the double deletion mutant. The potential roles that mTrx 5 may play in coping with nitrosative stress are discussed.

Cleavage of deoxyoxanosine-containing oligodeoxyribonucleotides by bacterial endonuclease V.

Oxanine (O) is a deamination product derived from guanine with the nitrogen at the N1 position substituted by oxygen. Cytosine, thymine, adenine, guanine as well as oxanine itself can be incorporated by Klenow Fragment to pair with oxanine in a DNA template with similar efficiency, indicating that oxanine in DNA may cause various mutations. As a nucleotide, deoxyoxanosine may substitute for deoxyguanosine to complete a primer extension reaction. Endonuclease V, an enzyme known for its enzymatic activity on uridine-, inosine- and xanthosine-containing DNA, can cleave oxanosine-containing DNA at the second phosphodiester bond 3' to the lesion. Mg2+ or Mn2+, and to a small extent Co2+ or Ni2+, support the oxanosine-containing DNA cleavage activity. All four oxanosine-containing base pairs (A/O, T/O, C/O and G/O) were cleaved with similar efficiency. The cleavage of double-stranded oxanosine-containing DNA was approximately 6-fold less efficient than that of double-stranded inosine-containing DNA. Single-stranded oxanosine-containing DNA was cleaved with a lower efficiency as compared with double-stranded oxanosine-containing DNA. A metal ion enhances the binding of endonuclease V to double-stranded and single-stranded oxanosine-containing DNA 6- and 4-fold, respectively. Hypothetic models of oxanine-containing base pairs and deaminated base recognition mechanism are presented.

Oxanine DNA glycosylase activity from Mammalian alkyladenine glycosylase.

Oxanine (Oxa) is a deaminated base lesion derived from guanine in which the N(1)-nitrogen is substituted by oxygen. This work reports the mutagenicity of oxanine as well as oxanine DNA glycosylase (ODG) activities in mammalian systems. Using human DNA polymerase beta, deoxyoxanosine triphosphate is only incorporated opposite cytosine (Cyt). When an oxanine base is in a DNA template, Cyt is efficiently incorporated opposite the template oxanine; however, adenine and thymine are also incorporated opposite Oxa with an efficiency approximately 80% of a Cyt/Oxa (C/O) base pair. Guanine is incorporated opposite Oxa with the least efficiency, 16% compared with cytosine. ODG activity was detected in several mammalian cell extracts. Among the known human DNA glycosylases tested, human alkyladenine glycosylase (AAG) shows ODG activity, whereas hOGG1, hNEIL1, or hNEIL2 did not. ODG activity was detected in spleen cell extracts of wild type age-matched mice, but little activity was observed in that of Aag knock-out mice, confirming that the ODG activity is intrinsic to AAG. Human AAG can excise Oxa from all four Oxa-containing double-stranded base pairs, Cyt/Oxa, Thy/Oxa, Ade/Oxa, and Gua/Oxa, with no preference to base pairing. Surprisingly, AAG can remove Oxa from single-stranded Oxa-containing DNA as well. Indeed, AAG can also remove 1,N(6)-ethenoadenine from single-stranded DNA. This study extends the deaminated base glycosylase activities of AAG to oxanine; thus, AAG is a mammalian enzyme that can act on all three purine deamination bases, hypoxanthine, xanthine, and oxanine.