Unveiling the mechanism of photothermal therapy in acne man-agement: targeting sebaceous gland ferroptosis via umbilical cord mesenchymal stem cell membrane-encapsulated Au-Ag-PDA.

Background: Branched gold and silver nanoparticles coated with polydopamine (Au-Ag-PDA) demonstrate high photothermal conversion efficiency. Utilizing umbilical cord mesenchymal stem cell membranes (MSCM) as an effective drug delivery system, our preliminary studies investigated the suppression of sebum secretion in sebaceous glands using MSCM-coated Au-Ag-PDA nano-particles (Au-Ag-PDA@MSCM) combined with 808 nm laser irradiation, showing potential for dermatological applications in acne treatment. Methods: This study employs proteomic analysis, complemented by subsequent techniques such as Western blotting (WB), small interfering RNA (siRNA), and transmission electron microscopy, to further investigate the differential mechanisms by which Au-Ag-PDA and Au-Ag-PDA@MSCM-mediated photothermal therapy (PTT) suppress sebum secretion. Results: Our proteomic analysis indicated mitochondrial respiratory chain damage in sebaceous gland tissues post-PTT, with further validation revealing ferroptosis in sebaceous cells and tissues. Acyl-CoA Synthetase Long-Chain Family Member 4 (Acsl4) has been identified as a critical target, with Au-Ag-PDA@MSCM demonstrating enhanced ferroptotic effects. Conclusion: These findings significantly advance our understanding of how PTT mediated by Au-Ag-PDA@MSCM nanoparticles reduces sebum secretion and underscore the pivotal role of MSCM in inducing ferroptosis in sebaceous glands, thus providing a robust theoretical foundation for employing PTT via specific molecular pathways in acne treatment.

A computationally efficient gradient-enhanced healing model for soft biological tissues.

Soft biological tissues, such as arterial tissue, have the ability to grow and remodel in response to damage. Computational method plays a critical role in understanding the underlying mechanisms of tissue damage and healing. However, the existing healing model often requires huge computation time and it is inconvenient to implement finite element simulation. In this paper, we propose a computationally efficient gradient-enhanced healing model that combines the advantages of the gradient-enhanced damage model, the homeostatic-driven turnover remodeling model, and the damage-induced growth model. In the proposed model, the evolution of healing-related parameters can be solved explicitly. Additionally, an adaptive time increment method is used to further reduce computation time. The proposed model can be easily implemented in Abaqus, requiring only a user subroutine UMAT. The effectiveness of proposed model is verified through a semi-analytical example, and the influence of the variables in the proposed model is investigated using uniaxial tension and open-hole plate tests. Finally, the long-term development of aneurysms is simulated to demonstrate the potential applications of the proposed model in real biomechanical problems.

Sensitivity analysis of the mechanical properties on atherosclerotic arteries rupture risk with an artificial neural network method.

Considering the differences between individuals, in this paper, an uncertainty analysis model for predicting rupture risk of atherosclerotic arteries is established based on a back-propagation artificial neural network. The influence of isotropy and anisotropy on the rupture risk of atherosclerotic arteries is analyzed, and the results demonstrate the effectiveness of the artificial neural network in predicting the rupture risk. Moreover, the rupture risk of atherosclerotic arteries at different inflation sizes are simulated. This study contributes to a better understanding of the underlying mechanisms of atherosclerotic arteries rupture and promotes the advancement of artificial neural networks in atherosclerosis research.

Dendrimer-conjugated isotretinoin for controlled transdermal drug delivery.

BACKGROUND: In the present study, we aimed to develop a novel isotretinoin delivery model for treating skin diseases, revealing its potential advantages in drug delivery and targeted therapy. Using a self-assembly strategy, we grafted a dendrimer, based on a well-defined branched structure for nanomedical devices, with a well-defined nanoarchitecture, yielding spherical, highly homogeneous molecules with multiple surface functionalities. Accordingly, a self-assembled dendrimer-conjugated system was developed to achieve the transdermal delivery of isotretinoin (13cRA-D). RESULTS: Herein, 13cRA-D showed remarkable controlled release, characterized by slow release in normal tissues but accelerated release in tissues with low pH, such as sites of inflammation. These release characteristics could abrogate the nonteratogenic side effects of isotretinoin and allow efficient skin permeation. Moreover, 13cRA-D exhibited high therapeutic efficacy in acne models. Based on in vitro and in vivo experimental results, 13cRA-D afforded better skin penetration than isotretinoin and allowed lesion targeting. Additionally, 13cRA-D induced minimal skin irritation. CONCLUSION: Our findings suggest that 13cRA-D is a safe and effective isotretinoin formulation for treating patients with skin disorders.

Minoxidil delivered via a stem cell membrane delivery controlled release system promotes hair growth in C57BL/6J mice.

Objective: Umbilical cord-derived mesenchymal stem cell membrane-loaded minoxidil (MXD) nanoparticles (STCM-MXD-NPs) were prepared to investigate their effects on hair growth in C57BL/6J mice. Methods: STCM-MXD-NPs were obtained by freeze-thawing and differential centrifugation, and their effects on hair growth were evaluated using C57BL/6J mice. The mRNA and protein expression levels of vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) were detected by real-time polymerase chain reaction and enzyme-linked immunosorbent assays, respectively. Protein expression levels of marker of proliferation Ki-67 (MKI67) and ß-catenin (CTNNB) in skin tissue were detected by immunohistochemistry. Results: STCM-MXD-NPs improved MXD solubility. They released the drug slowly, increasing its transdermal properties, accumulation in the skin, and content in the hair bulb tissues with a better efficacy than that of ordinary MXD. Moreover, STCM-MXD-NPs significantly upregulated the mRNA and protein levels of VEGF and IGF-1 and promoted the protein expression of MKI67 and CTNNB in mouse skin tissues, promoting mouse hair growth. Conclusion: Stem cell membrane-loaded MXD nanoparticles with slow-release properties increased MXD accumulation in the skin by improving its transdermal properties, increasing VEGF, IGF-1, MKI67, and CTNNB expression levels and promoting hair growth in C57BL/6J mice.

Correction: In vivo migration of Fe3O4@polydopamine nanoparticle-labeled mesenchymal stem cells to burn injury sites and their therapeutic effects in a rat model.

Correction for 'In vivo migration of Fe3O4@polydopamine nanoparticle-labeled mesenchymal stem cells to burn injury sites and their therapeutic effects in a rat model' by Xiuying Li et al., Biomater. Sci., 2019, 7, 2861-2872, DOI: 10.1039/C9BM00242A.

Anti-Inflammatory Effects of Magnetically Targeted Mesenchymal Stem Cells on Laser-Induced Skin Injuries in Rats.

INTRODUCTION: Mesenchymal stem cells (MSCs) are a promising resource for tissue regeneration and repair. However, their clinical application is hindered by technical limitations related to MSC enrichment at the target sites. METHODS: MSCs were labeled with magnetic Fe3O4 nanoparticles (NPs). We analyzed the effects of NP on cell proliferation, stem cell characteristics, and cytokine secretion. Furthermore, we induced NP-labeled MSC migration with an external magnetic field toward laser-induced skin wounds in rats and evaluated the associated anti-inflammatory effects. RESULTS: Fe3O4 NP application did not adversely affect MSC characteristics. Moreover, Fe3O4 NP-labeled MSCs presented increased anti-inflammatory cytokine and chemokine production compared with unlabeled MSCs. Furthermore, MSCs accumulated at the injury site and magnetic targeting promoted NP-labeled MSC migration toward burn injury sites in vivo. On day 7 following MSC injection, reduced inflammation and promoted angiogenesis were observed in the magnetically targeted MSC group. In addition, anti-inflammatory factors were upregulated, whereas pro-inflammatory factors were downregulated within the magnetically targeted MSC group compared with those in the PBS group. CONCLUSION: This study demonstrates that magnetically targeted MSCs contribute to cell migration to the site of skin injury, improve anti-inflammatory effects and enhance angiogenesis compared with MSC injection alone. Therefore, magnetically targeted MSC therapy may be an effective treatment approach for epithelial tissue injuries.

Stem cell membrane-coated isotretinoin for acne treatment.

BACKGROUND: Topical isotretinoin is commonly used to treat acne. However, topical isotretinoin has side effects and can hardly permeate through the stratum corneum, the most important skin barrier. Therefore, this study aimed to demonstrate the efficacy of nanoparticles as stable carriers with great curative effects, low side effects, and strong transdermal ability. RESULTS: In a rabbit model of hyperkeratinization, STCM-ATRA-NPs showed significant therapeutic efficacy. By contrast, negative therapeutic efficacy was observed in a golden hamster model of hyper sebum production. Scanning electron microscopy and Fourier transform infrared spectral analyses showed that nanoparticles could penetrate the stratum corneum. Western blotting demonstrated that the nanoparticles could enhance the transdermal efficacy of isotretinoin by reducing the effect of keratin and tight junction proteins. Further, nanoparticles enhanced endocytosis, thereby promoting drug penetration and absorption into the skin. CONCLUSION: STCM-ATRA-NPs were demonstrated to control isotretinoin release, reducing its side effects, and efficiently permeating through the skin by reducing the effect of keratin and tight junction proteins and enhancing endocytosis.

Stem Cell Membrane-Coated Au-Ag-PDA Nanoparticle-Guided Photothermal Acne Therapy.

The polydopamine coating on Au-Ag nanoparticles (Au-Ag-PDA) possess excellent photothermal conversion efficiency after absorbing near-infrared laser light. After the stem cell membrane (STCM) encapsulates Au-Ag-PDA (Au-Ag-PDA@STCM), the nanoparticles (NPs) exhibit less cytotoxicity, and further optimizing their efficiency in photothermal therapy. The photothermal activity of Au-Ag-PDA@STCM has not yet been reported. Therefore, in this study, the sebaceous gland cell line SZ95 and the golden hamsters were used to observe the photothermal effects of the Au-Ag-PDA@STCM. SZ95 cells were treated with various concen-trations of Au-Ag-PDA@STCM NPs. The photothermal effect on cell proliferation was analyzed after irradiating the cells with a 808 nm laser. After laser treatment of golden hamsters, the flank organs were observed at 4 different time points. Histological analysis was performed to observe tissue damage. The results suggest that Au-Ag-PDA@STCM NPs significantly inhibited the proliferation of sebaceous gland cells in vitro, and reduced the size of sebaceous glands and sebum secretion in vivo. Therefore, NPs can be used to treat acne by thermally injuring sebaceous gland cells.

Identification of Genes and Pathways Associated with Acne Using Integrated Bioinformatics Methods.

BACKGROUND: Acne is the most common skin inflammatory condition. The pathogenesis of acne is not fully understood. AIMS: We performed weighted gene co-expression network analysis (WGCNA) to select acne-associated genes and pathways. METHODS: GSE53795 and GSE6475 datasets including data from lesional and nonlesional skin of acne patients were downloaded from the NCBI Gene Expression Omnibus. Differentially expressed genes (DEGs) in lesions were identified following a false discovery rate <0.05 and | log2 fold change | ≥0.5. DEG-associated biological processes and pathways were identified. WGCNA analysis was performed to identify acne-associated modules. DEGs in the acne-associated modules were used for protein-protein interaction (PPI) network construction and Gene Set Enrichment Analysis (GSEA). Acne-associated candidate DEGs and pathways were identified together with items in the Comparative Toxicogenomics Database (CTD). RESULTS: A total of 2,140 and 1,190 DEGs were identified in GSE53795 and GSE6475 datasets, respectively, including 716 overlapping DEGs with similar expression profiles in the two datasets, which were clustered into 10 consensus modules. Two modules (brown and turquoise, 359 genes) were associated with acne phenotype. Of these 359 DEGs, 254 were enrolled in the PPI network. GSEA showed that these DEGs were associated with chemokine signaling pathway, cytokine-cytokine receptor interaction, and natural killer cell-mediated cytotoxicity. After identification in CTD, one pathway Cytokine-cytokine receptor interaction and 24 acne-associated DEGs, including IL1R1, CXCL1, CXCR4, CCR1, CXCL2 and IL1ß, were identified as candidates associated with acne. CONCLUSION: Our results highlight the important roles of the proinflammatory cytokines including IL1ß, CXCL1, CXCL2, CXCR4, and CCR1 in acne pathogenesis or therapeutic management.

In vivo migration of Fe3O4@polydopamine nanoparticle-labeled mesenchymal stem cells to burn injury sites and their therapeutic effects in a rat model.

Mesenchymal stem cell (MSC)-based therapy has emerged as a promising therapeutic strategy for tissue regeneration and repair. However, efficient targeted delivery to specific tissues remains an open challenge. Here, we non-invasively monitored the migration of MSCs labeled with Fe3O4@polydopamine nanoparticles (Fe3O4@PDA NPs) toward laser burn injury sites in a living rat model and evaluated the effects of the labeled MSCs at the injury site. The Fe3O4@PDA NPs could be effectively incorporated into the MSCs without any negative effects on stem cell properties. Furthermore, they enhanced the migration ability of the MSCs by up-regulating the expression level of C-X-C chemokine receptor type 4 (CXCR4). They also increased the secretion of some cytokines and the expression of healing-related genes in comparison with unlabeled MSCs. Labeled MSCs were intravenously administered into injured rats, and live imaging was performed to monitor MSC migration. Fluorescent signals of the labeled MSCs appeared at burn injury lesions 1 day after injection and then gradually increased up to 7 days. After 7 days, the group injected with the labeled MSCs showed less inflammation compared with those injected with the unlabeled MSCs. Additionally, the labeled MSC group showed increased cytokines and reduced pro-inflammatory factors compared with the unlabeled MSC group. The Fe3O4@PDA NPs enhanced stromal cell-derived factor-1/CXCR4-mediated MSC migration in vivo. Thus, we demonstrated the safety, feasibility, and potential efficacy of using the Fe3O4@PDA NPs for optimizing MSC-based therapeutic strategies for burn wound healing.

Fungicidal efficacy of photodynamic therapy using methylene blue against Sporothrix globosa in vitro and in vivo.

Sporothrix schenckii strains are the aetiological agents of sporotrichosis, which is endemic in China. The most common clinical manifestation of sporotrichosis is cutaneous and subcutaneous nodular lesions with lymphangitis involvement. Currently, antifungal therapy is commonly used to treat sporotrichosis, however, drug resistance and complications are the major concerns, especially in patients who have asymptomatic liver injury or existing liver disorders, children, and pregnant women. To assess the in vitro and in vivo antifungal efficacy of photodynamic therapy (PDT) using photosensitizer methylene blue against Sporothrix strains isolated from patients. A light-emitting diode (LED) lamp was used as the light source with a wavelength of 640 ± 10 nm. For the in vitro study, the presence of five Sporothrix strains was assayed following LED irradiation with and without photosensitizer (L + M + , L + M-), with photosensitizer alone (L-M + ), or no exposure to LED light or photosensitizer (L-M-). For the in vivo study, mice were infected with the fungi and then treated with sodium chloride (control group), antifungal itraconazole alone (itraconazole group), and a combination of antifungal itraconazole and PDT (itraconazole +PDT group), or PDT alone (PDT group). The results showed that, in vitro, PDT (L + M + ) effectively inhibited fungal growth at an energy density of 40 J/cm2. In vivo, itraconazole + PDT effectively inhibited growth of the fungus with the highest level of efficacy. PDT with methylene blue is an effective adjuvant therapy for resistant infections of Sporothrix.

Di-(2-ethylhexyl) phthalate induces precocious puberty in adolescent female rats.

OBJECTIVES: Nowadays, Di-(2-ethylhexyl) phthalate (DEHP) is widely used in different kinds of commercial products as a plasticizer. Previous studies have revealed that exposures to DEHP could be associated with precocious puberty in teenagers, but the exact mechanism is yet to be known. MATERIALS AND METHODS: In this study, 48 prepubertal Wistar female rats were randomly apportioned into 4 groups and orally treated with 0, 250, 500, and 1000 mg/kg/d DEHP from postnatal day 21 up to 4 weeks. Subsequently, we examined the indicators related to the initiation of sexual development. RESULTS: DEHP was able to shorten the vaginal opening time and prolong the estrous cycles of female rats. IGF-1 expression was significantly upregulated by 1000 mg/kg/d DEHP in the hypothalamus, and the hypothalamic, as well as serum levels of GH, were also upregulated by DEHP. It also caused decrements in serum levels of FSH, LH, and T and the increment in level of progesterone. Meanwhile, DEHP was able to exert its effect on the mRNA and protein expression levels of Kiss-1, GPR54, and GnRH in the hypothalamus in pubertal female rats. CONCLUSION: These findings are revealing that DEHP exposure more likely causes imbalances of hypothalamus functioning in pubertal female rats and thus induces precautious puberty in these animals.

Recombinant Phage Elicits Protective Immune Response against Systemic S. globosa Infection in Mouse Model.

Sporothrix globosa is a type of fungus that typically infects immunocompromised patients. Its prevention continues to pose a challenge. A 70-KDa glycoprotein (Gp70) of Sporothrix has been previously reported to protect host against infection from this fungus. Here, we displayed an epitope peptide (kpvqhalltplgldr) of Gp70 on the major coat protein (pIII), and investigated its efficiency as a vaccine for preventing S. globosa infection. The recombinant phage and the heat-killed S. globosa were used to immunize mice separately. In this study, we evaluated the humoral and cellular immune responses in the mice and demonstrated that recombinant phage could induce mice to produce a stronger immune response and generate antibodies to inhibit S. globosa infection. Furthermore, immunization with recombinant phage could increase the survival rate of S. globosa infection in mice. All these results together indicated that recombinant phages displaying kpvqhalltplgldr are a potential vaccine candidate against S. globosa infection.

Lower percentage of CD8+ T cells in peripheral blood of patients with sporotrichosis.

PURPOSE: To characterize the peripheral immunity and immunity response of patients with sporotrichosis, in this study we determined the lymphocyte subsets in the peripheral blood of Chinese patients with sporotrichosis. METHODS: In this retrospective study, peripheral blood was collected from 69 sporotrichosis patients (37, fixed cutaneous form; 32 lymphocutaneous) and 66 healthy controls. Lymphocyte subsets were analyzed using flow cytometry. RESULTS: Compared to controls, the percentage of CD8+ T cells was lower in sporotrichosis patients. The percentage of CD8+ T cells in peripheral blood tended to become lower with disease duration and disease severity, although the difference was not statistically significant for either acute, subacute and chronic patients or fixed cutaneous and lymphocutaneous patients. CONCLUSION: Our data indicate that the decrease of CD8+ T cells in peripheral blood of patients with sporotrichosis is associated with disease severity, although the difference was not statistically significant for either duration or clinical forms of the disease. Combining antifungal agents and immunomodulators in patients with long disease duration and lymphocutaneous may be more beneficial than antifungal monotherapy.

[Concentrations of PCDD/Fs in the atmosphere of Chongqing City and its seasonal variation].

As a comprehensive monitoring survey on polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) in Chongqing, 20 ambient air samples taken from 5 locations in four seasons were studied. The PCDD/F TEQ concentrations varied from 0.017 pg x m(-3) to 0.21 pg x m(-3). The average value was (0.094 +/- 0.054) pg x m(-3). The PCDD/F concentrations varied by locations and seasons, and the orders were: urban area > suburban area > background area, and Winter > Spring > Autumn > Summer. The concentrations of PCDD/Fs were 2.2-4.6 times higher in the winter than during the summer. The PCA results indicated that PCDD/F homologue pattern varied by seasons. The PCDD/F homologue pattern in particle dominated in winter and spring, and the pattern in gas dominated in summer and autumn. The mass concentration of PCDD/F congener was significantly positively correlated with that of SO2, NO2, PM10 and TSP, and insignificantly negatively correlated with that of O3, respectively. The results showed that spatial distribution and seasonal variation of atmospheric PCDD/Fs in Chongqing was consistent with that of these conventional indicators, and the PCDD/Fs pollution was closely related with the emission sources of SO2, NO2, PM10 and TSP.

[Atmospheric emission of PCDD/Fs from secondary aluminum metallurgy industry in the southwest area, China].

Five secondary aluminum metallurgy enterprises in the southwest area of China were measured for emissions of PCDD/Fs. The results indicated that the emission levels of PCDD/Fs (as TEQ) were 0.015-0.16 ng x m(-3), and the average was 0.093 ng x m(-3) from secondary aluminum metallurgy enterprises. Emission factors of PCDD/Fs (as TEQ) from the five secondary aluminum metallurgy enterprises varied between 0.041 and 4.68 microg x t(-1) aluminum, and the average was 2.01 microg x t(-1) aluminum; among them, PCDD/Fs emission factors from the crucible smelting furnace was the highest. Congener distribution of PCDD/F in stack gas from the five secondary aluminum metallurgies was very different from each other. Moreover, the R(PCDF/PCDD) was the lowest in the enterprise which was installed only with bag filters; the R(PCDF/PCDD) were 3.8-12.6 (the average, 7.7) in the others which were installed with water scrubbers. The results above indicated that the mechanism of PCDD/Fs formation was related to the types of exhaust gas treatment device. The results of this study can provide technical support for the formulation of PCDD/Fs emission standards and the best available techniques in the secondary aluminum metallurgy industry.