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Photodynamic therapy prevented the recurrence of lymphomatoid papulosis
摘要： Lymphomatoid papulosis (LyP) is a benign lymphoproliferative disorder which often takes indolent course. Topical steroid application and/or photochemotherapy are usually employed. Herein we report a case of LyP whose recurrence was successfully prevented by topical photodynamic therapy (PDT). A 55-year-old woman visited our hospital, with a five-year history of erythematous macules, papules, and erosions scattered on her trunk and extremities, and concentrated especially on her left thigh. She had been treated with topical potent corticosteroid. Although most of the skin lesions resolved within a few weeks, new papules had continuously appeared. The biopsy from the left thigh revealed perivascular dense infiltration of small lymphocytes admixed with large lymphocytes. The large lymphocytes were positive for CD3, CD4, and CD30. Whole body CT scan did not disclose visceral or lymph node involvement. The blood examination data were unremarkable. The diagnosis of LyP was established. Photochemotherapy with psoralen and UVA on her whole body, once a week for three months could not prevent the recurrence of the papules. Based on the successful treatment of mycosis fungoides with PDT [1], we applied PDT with topical 20% aminolevulinic acid (ALA) on her left thigh. The PDT-treated area developed hematoma within a day, as we observed in mycosis fungoides on PDT [1]; it gradually resolved in several weeks. One year after PDT, LyP lesion did not recur in the PDT-treated area, although a few papules appeared on her extremities every month. In our previous report of mycosis fungoides treated with PDT [1], the PDT-treated area formed hematoma. The biopsy taken five days after PDT revealed totally degenerated blood vessels with massive hemorrhage in the dermis. In order to investigate the mechanism of PDT on LyP, we took a biopsy immediately after PDT, before developing hematoma. The biopsy taken from pigmented lesion revealed scattered perivascular infiltration of small lymphocytes. The reticular dermis and capillary endothelium were edematous. Apoptotic cells were not found with hematoxylin and eosin stain or with TUNEL technique (data not shown). Immunostain for high mobility group box 1 (HMGB1) was positive in the cytoplasm of lymphocytes and vascular endothelium. Calreticulin immunostain was positive on the surface of vascular endothelium and sweat gland apparatus. Although the direct effect of PDT on actinic keratosis usually appears immediately after the procedure, we could not find an apparent change histologically, immediately after PDT, however, the treated area formed hematoma within a day. Thus, we sought an indirect mechanism to induce cell death and vascular change, which took several hours or days. Along with the result of immunostain for HMGB1 and calreticulin, we assumed that immunogenic cell death (ICD) might occur in the PDT-treated lesion. HMGB1 secretion from nuclei and calreticulin binding to cell membrane are among the danger-associated molecular patterns (DAMPs), which are the features most commonly associated with ICD [2]. ICD is a self-defense mechanism against malignant neoplasms. Once neoplastic cells are damaged by chemotherapeutic agents or PDT [2], DAMPs are relocated to the surface of the cells, and released from the damaged cells. Then the DAMPs stimulate surrounding dendritic cells and Natural Killer cells, and induce apoptosis in the neoplastic cells. Thus, this process is not tumor-specific, but can induce broad degeneration in the surrounding tissue. Among the chemicals utilized in PDT, only hypericin [3] and glycoconjugated chlorin [4] were proved to induce ICD, so far. Herein we demonstrated that ALA could induce DAMPs, and speculate that ALA-PDT may work via ICD mechanism. LyP lesions can appear anywhere on the body, occasionally in a concentrated manner. In the early report of LyP treated with ALA-PDT [5], the authors observed not only its efficacy on the treatment-resistant lesion, but a preventive effect, as we experienced. PDT can be a good candidate for a field therapy of LyP, as suggested in the treatment of actinic keratosis [6].
关键词： HMGB1,immunogenic cell death,calreticulin
更新于2025-09-23 15:23:52
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Exosomes Derived From Mesenchymal Stem Cells Modulate miR-126 to Ameliorate Hyperglycemia-Induced Retinal Inflammation Via Targeting HMGB1
摘要： PURPOSE. In this study, we aim to investigate whether mesenchymal stem cell (MSC)-derived exosomes (MSC-Exos) could regulate hyperglycemia-induced retinal inflammation by transferring microRNA-126 (miR-126). METHODS. MSC-Exos were isolated from the media of human umbilical cord-derived mesenchymal stem cells (hUCMSCs), and this isolation was followed by the transfer of miR-126. MSC-Exos or MSC-Exos overexpressing miR-126 were intravitreally injected into diabetic rats in vivo and were cocultured with high glucose-affected human retinal endothelial cells (HRECs) in vitro. Plasma samples were obtained from the vitreous of rats and from HREC cells after treatment for ELISA assay. Retinal sections were examined using immunohistochemistry. RT-PCR and Western blotting were conducted to assess the levels of high-mobility group box 1 (HMGB1), NLRP3 inflammasome, and NF-jB/P65 in retinas and HRECs. RESULTS. Our results showed that hyperglycemia greatly increased inflammation in diabetic rats or HRECs exposed to high glucose, increasing the levels of caspase-1, interleukin-1b (IL-1b) and IL-18. The administration of MSC-Exos could effectively reverse this reaction. Compared to control MSC-Exos, MSC-Exos overexpressing miR-126 more successfully suppressed the HMGB1 signaling pathway and suppressed inflammation in diabetic rats. The administration of miR-126-expressing MSC-Exos significantly reduced high glucose-induced HMGB1 expression and the activity of the NLRP3 inflammasome in HRECs. CONCLUSIONS. miR-126 expression in MSC-Exos reduces hyperglycemia-induced retinal inflammation by downregulating the HMGB1 signaling pathway.
关键词： HMGB1,exosome,NLRP3 inflammasome,miR-126,mesenchymal stem cell
更新于2025-09-19 17:15:36
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Frequency Calibration and Stabilization of the Cooling Laser of Ytterbium Lattice Clock with Molecular Iodine Spectroscopy
摘要： Glycyrrhetinic acid (GA), the main bioactive substances of glycyrrhiza uralensis Fisch, has been reported to exhibit hepatoprotective and anti-inflammatory properties. However, the effects and underlying mechanisms of GA in liver ischemia/reperfusion (I/R) injury remain elusive. In this study, mice were pretreated with GA (100 mg/kg) three times a day by gavage prior to I/R injury, and then hepatic histopathological damages, biochemical parameters and inflammatory molecules were evaluated. We found that mice performed with liver I/R showed a significantly increase in plasma aminotransferase (ALT), aspartate aminotransferase (AST), liver cell apoptosis and infiltration of neutrophils compared with the control group. GA pretreatment notably improved liver function, histopathology of liver tissues, and lowered liver cell apoptosis and infiltration of neutrophils. Besides, further analysis indicated that GA pretreatment reduced I/R-induced expression of extracellular HMGB1, inhibited activation of TLR4 and following phosphorylation of IRAK1, ERK, P38 and NF-κB, and attenuated TNF-α and IL-1β production. These data suggested that GA protected against liver I/R injury through a HMGB1-TLR4 signaling pathway and it might be a promising drug for future clinical use in liver transplantation.
关键词： Glycyrrhetinic acid,Inflammation,TLR4,Apoptosis,HMGB1,Liver ischemia/reperfusion injury
更新于2025-09-11 14:15:04