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Breast cancer is the most common malignant tumor and ranks as the leading cause of cancer-related death among women. Although endocrine and targeted therapy have obtained positive curative effects, the high recurrence rate and mortality associated with drug resistance remain obstacles. Solid evidence indicates that lysophosphatidylcholine acyltransferase 1 (LPCAT1) plays a key role during tumorigenesis. Notably, LPCAT1 upregulates cancer-related Erbb signaling pathways by affecting the lipid microenvironment around the cell membrane. However, its function and mechanism in breast cancer are still elusive. The regulation of long noncoding RNAs (lncRNAs) on multiple molecules is closely related to the occurrence and development of breast cancer. At present, most studies contend that lncRNAs facilitate downstream target gene expression by regulating ceRNAs, while others suggest that lncRNAs may function as upstream modulators, inhibiting gene expression by promoting splicing of per-miRNAs. In this study, the expression and prognosis of LPCAT1 and noncoding RNA (LINC01176) were analyzed in multiple tumors. Data in The Genotype-Tissue Expression (GTEx) indicated that LPCAT1 may be a potential oncogene in breast cancer, while LINC01176, as a new noncoding RNA, may have an inhibitory effect on breast cancer. A series of bioinformatic analyses, including expression, correlation, and prognostic analyses, confirmed that the expression of LPCAT1 is related to the regulation of the noncoding RNA (lncRNA) LINC01176. Finally, the LINC01176/hsa-miR-218-5p/LPCAT1 axis was identified as the most likely upstream lncRNA-related pathway for LPCAT1 in breast cancer. Mechanistically, we found that LPCAT1, LINC01176, and hsa-miR-218-5p are related to various tumor-related signaling pathways by KEGG enrichment analysis, including the Erbb signaling pathway, which is closely related to breast cancer, and tumor angiogenesis-related VEGF and Notch signaling pathways. Moreover, the LPCAT1 level was significantly positively associated with HER2, PC, VEGF, and NOTCH, while LINC was significantly negatively associated with HER2, PC, and NOTCH. In summary, our study suggests that LPCAT1 contributes to poor prognosis in breast cancer and that we can improve the prognosis of breast cancer by regulating the LINC01176/hsa-miR-218-5p/LPCAT1 axis.

Senescence is a cellular process that can be initiated by certain stressors such as UVA irradiation. The mechanism by which skin cells protect themselves from the UVA-induced senescence has not been fully investigated. Here, we demonstrate that Bach2 modulates the extent of UVA-induced photoaging through regulation of autophagy in skin fibroblasts. In fact chronic exposure of skin fibroblasts to UVA resulted in a significant decrease in Bach2 expression, both in vitro and in vivo. In addition, knockdown of Bach2 in skin fibroblasts led to an increased expression of cell senescence-related genes, which further enhanced the UVA irradiation-induced photoaging. On the other hand, the overexpression of Bach2 resulted in a decrease in the expression of cell senescence-related genes. We also demonstrate that the knockdown of Bach2 in skin fibroblasts can lead to a decreased expression of autophagy-related genes and vice versa, suggesting that autophagy is involved in Bach2-mediated regulation of senescence in skin fibroblasts. Additionally, inhibition of autophagy with autophagy inhibitor 3-MA suppressed the expression of autophagy-related proteins and promoted cell senescence. Furthermore, knockout of Atg5 or Atg7 in embryonic mouse fibroblasts led to a significant increase in the expression of cell senescence-related genes. Immunoprecipitation assays further demonstrated that Bach2 directly interacts with Beclin-1, Atg3, Atg7, and LC3 in fibroblasts. Taken together, these findings revealed a critical role for Bach2 in suppressing the UVA irradiation-induced cell senescence via autophagy in skin fibroblasts. Bach2 can therefore be a potential target for the therapy of UV-induced photoaging because of its ability to regulate the process of autophagy in the skin.

Objectives: To investigate the effects of low-dose aminolevulinic acid photodynamic therapy (ALA-PDT) on photoaging in human dermal fibroblasts (HDFs) and to explore the mechanism of Nuclear factor erythroid 2-related factor 2(Nrf2)-mediated photorejuvenation in vitro. Methods: A photoaging model was established through repeated exposure of HDFs to UVA. Total superoxide dismutase (SOD) expression was detected by a SOD activity assay. Nrf2 was knocked down through adenovirus infection, and successful knockdown was confirmed by Western blot analysis and quantitative polymerase chain reaction. Results: Sustained exposure to UVA induced photoaging in HDFs. Total SOD activity was significantly increased by low-dose aminolevulinic acid (ALA)-PDT. Upon application of low doses of ALA-PDT to photoaging HDFs, Nrf2 was translocated to the nucleus; in addition, the expression of Nrf2, transforming growth factor-β1 (TGF-β1), type I and III collagen (COL1 and COL3), heme oxygenase 1 (HO-1), and p-ERK was increased, while the expression of matrix metalloproteinase 9 (MMP-9) was decreased. However, after Nrf2 was knocked down in HDFs, the expression of TGF-β1, COL1, COL3, and HO-1 was significantly decreased, while the expression of MMP-9 was increased. Conclusion: This study revealed that low-dose ALA-PDT decreases UVA-mediated photoaging through an Nrf2-mediated antioxidant effect.

Photodynamic therapy (PDT) is a promising new method to eliminate microbial infection and promote wound healing. Its effectiveness has been confirmed by some studies; however, the mechanisms of PDT in wound healing remain obscure. We used mouse skin wounds infected withPseudomonas aeruginosaas a research object to explore the therapeutic effects and mechanisms of 5-aminolevulinic acid photodynamic therapy (ALA-PDT). ALA-PDT treatment significantly reduced the load ofP. aeruginosain the wound and surrounding tissues and promoted the healing of skin wounds in mice. Hematoxylin-eosin (HE) and Sirius red staining showed that ALA-PDT promoted granulation tissue formation, angiogenesis, and collagen regeneration and remodeling. After ALA-PDT treatment, the expression of inflammatory factors (TNF-α and IL-1β) first increased and then decreased, while the secretion of growth factors (TGF-β-1 and VEGF) increased gradually after treatment. Furthermore, ALA-PDT affected the polarization state of macrophages, activating and promoting macrophages from an M1 to an M2 phenotype. In conclusion, ALA-PDT can not only kill bacteria but also promote wound healing by regulating inflammatory factors, collagen remodeling and macrophages. This study further clarifies the mechanism of PDT in the healing of infectious skin wounds and provides further experimental evidence for its clinical treatment of skin wounds infected byP. aeruginosa.

Objective To investigate low-level ALA-PDT (Aminolevulinic acid photodynamic therapy) effects on photorejuvenation in vitro and in vivo, exploring the basic mechanism of Bach2 involved in PDT treatment in photoaging. Method Photoaging model was established by UVA chronic irradiation in human fibroblasts and mice skins. Cell viability was determined by MTS assay and cell senescence was detected by SA-β-gal activity. PDT treatment and Bach2 knockdown with adenovirus in fibroblasts were confirmed by Western blot. Results UVA chronic irradiation induced photoaging in vitro and in vivo. Treatment of low-level PDT reduced photoaging by decreasing SA-β-gal activity and cell senescence-related proteins levels of p16 and p21 in fibroblasts. Moreover, low-level PDT treatment accompany with Bach2 accumulation increased in fibroblasts and in mice skin tissues. Bach2 knockdown with adenovirus induced cell senescence and Bach2 depletion with PDT treatment some extent decreased SA-β-gal activity, but was with no significant change of Bach2 itself and p16 protein levels in fibroblasts. Conclusion Low-level PDT treatment decreased skin photoaging which might be through up-regulating Bach2.

Chromoblastomycosis (CBM) is a prevalent implantation fungal infection. Patients with CBM show chronic granulomatous hyperplasia with ulcers and exudation. It may cause incapacity for labor in some severe clinical forms and it is often refractory to antifungal therapies. There is no optimal treatment. Here we report a case of a 71-year-old male farmer with refractory CBM who was successfully treated with 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) and Itraconazole in 2 months. Clinical cure was achieved with no obvious side effects.