Daily Cosmetic Research Analysis
Analyzed 33 papers and selected 3 impactful papers.
Summary
Top studies spanned translational dermatology, oncology, and reconstructive surgery. A mechanistic study repurposes topical propofol to suppress psoriasiform inflammation via KEAP1/Nrf2/HO-1 activation; another demonstrates paeoniflorin-induced therapeutic senescence in melanoma through a calpain1/ERK5/p27 axis. Clinically, reverse expansion improved autologous fat graft retention and patient-reported outcomes in breast reconstruction.
Research Themes
- Drug repurposing and antioxidant pathways in inflammatory skin disease
- Therapeutic senescence and targeted signaling in melanoma
- Technique innovation to enhance autologous fat graft retention in reconstruction
Selected Articles
1. Skin delivery and anti-inflammatory effects of the anesthetic propofol against psoriasiform lesions through KEAP1/Nrf2/HO-1 pathway activation.
Topical propofol reduced proinflammatory cytokines in keratinocytes, macrophages, and neutrophils via KEAP1 downregulation and Nrf2/HO-1 activation, blocked macrophage migration, showed measurable dermal delivery, and improved imiquimod-induced psoriasiform lesions in mice. Findings support drug repurposing for antipsoriatic therapy with a topical route to minimize systemic exposure.
Impact: This work links a clinically familiar anesthetic to a defined antioxidant pathway (KEAP1/Nrf2/HO-1) with multi-system validation and in vivo efficacy, opening a practical topical strategy for psoriasis management.
Clinical Implications: Suggests a feasible topical adjunct or alternative for psoriasis that targets oxidative stress/inflammation while avoiding systemic anesthesia-related risks; warrants formulation optimization and early-phase clinical trials.
Key Findings
- Propofol reduced IL-6, IL-8, and CXCL1 in activated keratinocytes and suppressed cytokines in macrophages and neutrophils.
- Mechanism involved KEAP1 downregulation with consequent Nrf2 and HO-1 upregulation; DPPH scavenging reduced by 47%.
- Topical propofol improved imiquimod-induced psoriasiform lesions, reducing erythema, acanthosis, immune infiltration, cytokines, and epidermal thickness.
- Dermal delivery was quantifiable (1.2 nmol/mg in intact pig skin; 3.7 nmol/mg after SC lipid removal), and docking suggested interaction with SC ceramides.
- Propofol blocked macrophage migration induced by keratinocyte-conditioned medium.
Methodological Strengths
- Multi-system validation across keratinocytes, macrophages, neutrophils, ex vivo skin, and an in vivo imiquimod mouse model
- Mechanistic pathway interrogation (KEAP1/Nrf2/HO-1) supported by immunoblotting, antioxidant assays, and in silico docking
Limitations
- Preclinical study without human clinical data or long-term safety profiling of topical propofol in psoriasis
- Dose, formulation, and comparative efficacy versus standard therapies were not optimized or tested
Future Directions: Optimize topical formulations, perform pharmacokinetics/toxicology, and advance to phase I/II trials comparing with standard topical agents (e.g., corticosteroids, vitamin D analogs) and exploring biomarkers of Nrf2 activation.
Propofol is a commonly used anesthetic for sedation during surgery. This drug is reported to exhibit nonanaesthetic immunomodulatory and anti-inflammatory effects. Herein, we investigated the impact of topical propofol delivery with the aim of mitigating psoriatic inflammation. The antipsoriatic potency of propofol was evaluated in a cell-based study in which keratinocytes, macrophages, and neutrophils were used as models. A significant reduction in the proinflammatory effectors interleukin (IL)-6, IL-8, and CXC motif chemokine ligand (CXCL)1 was found in activated keratinocytes (HaCaT) treated with propofol. This reduction could enable baseline control. Immunoblotting suggested that the antioxidant enzymes nuclear factor erythroid 2-related factor (Nrf)2 and heme oxygenase (HO)-1 were involved in the protective effect of propofol on keratinocyte stimulation. The increase in Nrf2 and HO-1 was mediated by kelch-like ECH-associated protein (KEAP)1 downregulation. Propofol presented scavenging activity and decreased 2,2-diphenyl-1-picrylhydrazyl (DPPH) by 47%. The downregulation of cytokines/chemokines in activated macrophages (differentiated THP-1) and mouse neutrophils was also found after propofol treatment. Macrophage migration triggered by the conditioned medium of activated keratinocytes could be blocked with the intervention of propofol. The absorption level of propofol (3 mM) into intact pig skin was 1.2 nmol/mg. Skin deposition was increased to 3.7 nmol/mg after SC lipid removal to mimic psoriasiform skin. In silico molecular docking demonstrated the facile interaction of propofol with ceramides in the stratum corneum (SC). The treatment of imiquimod (IMQ)-sensitized mice with topical propofol suppressed erythema, acanthosis, and macrophage/neutrophil infiltration. Propofol also dramatically decreased cytokine/chemokine levels and epidermal thickness in the lesion. In summary, propofol exhibits anti-inflammatory and antioxidant properties to treat psoriasiform lesions. Topical propofol delivery is useful as an ideal route to accomplish antipsoriatic therapy and avoid systemic effects.
2. Paeoniflorin promotes therapeutic senescence in melanoma through endoplasmic reticulum stress and the calpain1/ERK5/p27 axis.
Paeoniflorin induced therapeutic senescence in melanoma via ER stress, calpain1 activation, ERK5 degradation, and p27 upregulation, reducing tumor growth and metastasis in mice; effects were reversed by calpain1 inhibition/knockdown. Prognostic gene associations (RRAS, CDKN1B vs LAMA1, CDC25A) contextualize clinical relevance.
Impact: Defines a druggable calpain1/ERK5/p27 axis for senescence induction in melanoma with in vivo validation, offering a mechanistically grounded strategy complementary to current therapies.
Clinical Implications: Supports development of senescence-inducing therapeutics and biomarker-driven trials (e.g., calpain1/ERK5 status) as adjuncts to immunotherapy/targeted therapy in melanoma.
Key Findings
- Paeoniflorin induced DNA damage, G2/M arrest, and senescence with enhanced ER stress and increased calpain1 activity; ERK5 expression decreased.
- Calpain1 inhibition or knockdown reversed paeoniflorin’s effects, establishing pathway dependence.
- In mouse models, paeoniflorin reduced tumor growth and metastasis; effects were lost with calpain1 silencing.
- Bioinformatics linked high RRAS/CDKN1B to favorable prognosis and high LAMA1/CDC25A to poor outcomes in SKCM.
Methodological Strengths
- Integrated in vitro, in vivo, and bioinformatic approaches with mechanistic validation via inhibitors and siRNA
- Use of PET/CT, histopathology, and metastasis assays to demonstrate in vivo efficacy and biological plausibility
Limitations
- Preclinical nature without human safety/pharmacokinetic data and limited assessment across melanoma subtypes
- Herbal-derived compound with potential batch variability; off-target effects not fully excluded
Future Directions: Define dose-response and PK/PD, assess toxicity, test combinations with immune checkpoint inhibitors/targeted agents, and develop biomarkers (calpain1/ERK5/p27) for patient selection.
BACKGROUND: Skin cutaneous melanoma (SKCM) is a highly aggressive malignancy with increasing global incidence and limited therapeutic options in advanced stages. Cellular senescence, characterized by irreversible growth arrest and tumor suppression, has emerged as a promising therapeutic approach. PURPOSE: This study aimed to investigate the anti-tumor and senescence-inducing effects of paeoniflorin on SKCM and to elucidate its underlying molecular mechanisms. STUDY DESIGN: Paeoniflorin was evaluated through in vitro, in vivo, and bioinformatic analyses to determine its impact on melanoma progression and to clarify the involvement of the endoplasmic reticulum (ER) stress/calpain1/ERK5 signaling pathway. METHODS: Publicly available SKCM datasets were analyzed to evaluate the correlation between senescence-associated genes (RRAS, CDKN1B, LAMA1, and CDC25A) and patient prognosis. The effects of paeoniflorin on melanoma cells were examined by immunofluorescence, β-galactosidase staining, western blotting, electron microscopy, and calpain activity assays. Chemical inhibitors and siRNA were applied to verify the functional role of calpain1. Positron emission tomography/computed tomography (PET/CT) imaging, histopathological analysis, and metastasis assays were performed to assess the in vivo efficacy of paeoniflorin. RESULTS: Bioinformatic analysis revealed that high expression of RRAS and CDKN1B was associated with favorable prognosis, whereas elevated LAMA1 and CDC25A indicated poor survival outcomes in SKCM. Paeoniflorin treatment induced DNA damage, G2/M phase arrest, and senescence in melanoma cells, accompanied by enhanced ER stress, increased calpain1 activity, and downregulated ERK5 expression. Inhibition or knockdown of calpain1 reversed these effects. In mouse models, paeoniflorin markedly reduced tumor growth and metastasis, effects that were abolished by calpain1 silencing. Mechanistically, paeoniflorin triggered calpain1-dependent ERK5 degradation and p27 upregulation, leading to cellular senescence and tumor suppression. CONCLUSIONS: Paeoniflorin induces melanoma cell senescence through the ER stress/calpain1/ERK5/p27 signaling axis, suggesting its potential as a novel therapeutic strategy against SKCM.
3. Reverse expansion-assisted high-quality autologous fat grafting in breast reconstruction: A retrospective comparative study.
In 55 post-mastectomy patients, reverse expansion prior to subsequent autologous fat grafting significantly increased second-graft retention and improved BREAST-Q psychosocial well-being and breast satisfaction compared with fat grafting alone, without added complications. RE can provide sufficient skin and better contouring while reducing rounds of grafting.
Impact: Provides comparative clinical evidence that a practical perioperative strategy improves fat graft retention and patient-reported outcomes in breast reconstruction.
Clinical Implications: Consider RE to precondition the recipient site before staged fat grafting to enhance retention, reduce the number of sessions, and improve satisfaction in post-mastectomy reconstruction.
Key Findings
- Among 55 patients (RE+FG n=27; FG n=28), initial graft retention and preoperative scores did not differ between groups.
- Second fat graft retention (first after RE) was significantly higher in the RE+FG group than FG alone (P<0.001).
- BREAST-Q postoperative scores for psychosocial well-being and breast satisfaction were significantly better with RE+FG (P<0.05).
- RE facilitated sufficient skin envelope and contour improvement without relying on patient compliance.
Methodological Strengths
- Comparative cohort design with objective retention metrics and validated patient-reported outcome measures (BREAST-Q)
- Clear statistical differences (e.g., P<0.001 for second-graft retention) supporting effect size
Limitations
- Single-center, retrospective design with potential selection bias and unmeasured confounders
- Limited details on follow-up duration and standardized imaging/volumetry methods
Future Directions: Prospective, multicenter randomized studies with standardized volumetric imaging to confirm efficacy, optimize timing/parameters of RE, and assess long-term durability and cost-effectiveness.
BACKGROUND: Reverse expansion (RE) combined with fat grafting (FG) is a relatively innovative method used for breast reconstruction following mastectomy for breast cancer. Using an expanded subcutaneous adipose tissue layer as the recipient area seems to promote the retention of subsequent grafts. To further validate, the study retrospectively compared clinical outcomes in patients who underwent FG with and without RE for breast reconstruction. METHODS: This study included patients diagnosed with breast cancer who underwent unilateral mastectomy followed by breast reconstruction with high-quality autologous FG at our department between January 2019 and December 2023. The patients were divided into two groups, those who underwent FG plus RE group and those who underwent FG alone. Demographic and clinical characteristics, FG retention rates, BREAST-Q scores, and complications were compared in the two groups. RESULTS: The present study included 55 patients, 27 in the FG+RE group and 28 in the FG group. Preoperative scores and fat retention rates of the first FG did not differ significantly between these two groups (P>0.05 each). The retention rate of the second FG (i.e., the first FG after RE) was significantly higher in the FG+RE group than in the FG group (P<0.001). A comparison of BREAST-Q postoperative scores in the two groups showed that scores on two subscales, psychosocial well-being and satisfaction with breasts, were significantly superior in the FG+RE than in the FG group (P<0.05 each) CONCLUSIONS: Expander-assisted FG based on the RE strategy can improve graft retention and reduce the number of rounds of FG. Moreover, reverse expansion can result in sufficient skin and improve breast contouring without relying on patient compliance.