Jinjing Jia

Activation of Erk and p53 regulates copper oxide nanoparticle-induced cytotoxicity in keratinocytes and fibroblasts

Copper oxide nanoparticles (CuONP) have attracted increasing attention due to their unique properties and have been extensively utilized in industrial and commercial applications. For example, their antimicrobial capability endows CuONP with applications in dressings and textiles against bacterial infections. Along with the wide applications, concerns about the possible effects of CuONP on humans are also increasing. It is crucial to evaluate the safety and impact of CuONP on humans, and especially the skin, prior to their practical application. The potential toxicity of CuONP to skin keratinocytes has been reported recently. However, the underlying mechanism of toxicity in skin cells has remained unclear. In the present work, we explored the possible mechanism of the cytotoxicity of CuONP in HaCaT human keratinocytes and mouse embryonic fibroblasts (MEF). CuONP exposure induced viability loss, migration inhibition, and G2/M phase cycle arrest in both cell types. CuONP significantly induced mitogen-activated protein kinase (extracellular signal-regulated kinase [Erk], p38, and c-Jun N-terminal kinase [JNK]) activation in dose- and time-dependent manners. U0126 (an inhibitor of Erk), but not SB 239063 (an inhibitor of p38) or SP600125 (an inhibitor of JNK), enhanced CuONP-induced viability loss. CuONP also induced decreases in p53 and p-p53 levels in both cell types. Cyclic pifithrin-α, an inhibitor of p53 transcriptional activity, enhanced CuONP-induced viability loss. Nutlin-3α, a p53 stabilizer, prevented CuONP-induced viability loss in HaCaT cells, but not in MEF cells, due to the inherent toxicity of nutlin-3α to MEF. Moreover, the experiments on primary keratinocytes are in accordance with the conclusions acquired from HaCaT and MEF cells. These data demonstrate that the activation of Erk and p53 plays an important role in CuONP-induced cytotoxicity, and agents that preserve Erk or p53 activation may prevent CuONP-induced cytotoxicity.

Psoriasin, A Multifunctional Player in Different Diseases

Psoriasin (S100A7) is one of the members in the S100 protein family. It was first discovered as a protein abundantly expressed in psoriatic keratinocytes. Psoriasin has been implicated in a wide range of intracellular and extracellular functions, including regulation of calcium homeostasis, cell proliferation, differentiation, apoptosis, cell invasion and motility, cytoskeleton dynamics, protein phosphorylation, regulation of transcriptional factors, immune responses, chemotaxis, inflammation and pluripotency. Altered expression of psoriasin was shown to associate with a broad range of diseases, including inflammatory and immune disorders and tumors. Many lines of evidence suggested that psoriasin exerts its distinct functions through alterations in both intracellular and extracellular pathways and results alteration in gene expression. In this review, we summarize the multiple function of psoriasin and the underlying mechanisms and discuss the potential role of psoriasin as one of the biomarkers and therapeutic targets for multiple diseases.

Shikonin induces apoptosis of HaCaT cells via the mitochondrial, Erk and Akt pathways

Shikonin, which is a major ingredient of the traditional Chinese herb Lithospermum erythrorhizon, possesses various biological functions, including antimicrobial, anti-inflammatory, and antitumor activities. The present study aimed to determine the molecular mechanisms underlying the effects of shikonin on HaCaT cell apoptosis. Treatment with shikonin significantly inhibited the viability of HaCaT cells in a dose- and time-dependent manner, and promoted cell cycle arrest at G0/G1 phase and apoptosis. In addition, shikonin treatment reduced the mitochondrial membrane potential and induced reactive oxygen species generation. The results of a western blot analysis demonstrated that shikonin significantly activated caspase 3 expression, downregulated B-cell lymphoma 2 (Bcl-2) expression, and upregulated Bcl-2-associated X protein and Bcl-2 homologous antagonist killer expression in a dose-dependent manner in HaCaT cells. Furthermore, shikonin decreased extracellular signal-regulated kinase (Erk) and Akt phosphorylation. These results indicated that shikonin may exert its anti-proliferative effects by inducing apoptosis via activation of the mitochondrial signaling pathway and inactivation of the Akt and Erk pathways in HaCaT cells. Therefore, the present study suggested that shikonin may have potential as a component of therapeutic strategies for the treatment of skin diseases.

Extranodal natural killer/T-cell lymphoma, nasal type, involving the skin, misdiagnosed as nasosinusitis and a fungal infection: A case report and literature review.

The present study reports a case of extranodal natural killer (NK)/T-cell lymphoma, nasal type, involving the skin. The clinical manifestations, pathological characteristics, treatment and prognosis of the case were analyzed to improve the clinical diagnosis and treatment for this disease. The patient was a 56-year-old male, presenting with dark red nodules and plaques that had been visible on the nose for half a year. Based on the skin lesions and histopathological and immunohistochemical examination results, the patient was diagnosed with extranodal NK/T-cell lymphoma, nasal type. This disease has unique histopathological and immunohistochemical features and a high malignancy. The condition tends to be misdiagnosed and has a poor prognosis, but seldom involves the skin. In the present case, only radiotherapy was performed, with no relapse occurring within 6 months.

Lymphomatoid papulosis misdiagnosed as pityriasis lichenoides et varioliformis acuta: Two case reports and a literature review

The aim of this study was to improve the level of diagnosis and differential diagnosis of lymphomatoid papulosis (LyP). Two cases of type B LyP were identified and the literature was reviewed to summarize the clinical outcomes and pathology of LyP and its treatment. The two patients exhibited symptoms with papulonodular lesions, the centers of which gradually underwent ulceration and necrosis. CD30, a helper T-cell marker specifically expressed in tumor cells was analyzed by immunohistochemical staining and the result showed that CD30-negative or only scattered CD30-positive cells were present. Therefore, a diagnosis of type B LyP was made. A fairly good curative effect was achieved following treatment with retinoic acid, glucocorticoids and immunomodulatory drugs. LyP is a type of low-level malignant lymphoma and is easily misdiagnosed as pityriasis lichenoides et varioliformis acuta and other diseases. In order to avoid under diagnosis and misdiagnosis, doctors should evaluate suspected patients by histopathological and immunohistochemical examination.

Antimicrobial peptide LL-37 promotes YB-1 expression, and the viability, migration and invasion of malignant melanoma cells

The cathelicidin antimicrobial peptide, LL-37, is a multifunctional peptide with a broad spectrum of antimicrobial activities, such as chemotaxis and neutralizing endotoxins. Previous studies have demonstrated that it LL-37 serves a functional role in the development of numerous types of cancer including ovarian, breast, prostate and lung cancer. However, its role in the development of malignant melanoma (MM) remains unclear. To determine the role of LL-37 and the potential interaction with Y-box binding protein 1 (YB-1) in MM, RNA interference, western blot, reverse transcription-quantitative polymerase chain reaction, MTT and Transwell assays were performed. The current study demonstrated that LL-37 induced YB-1 expression, and increased tumor cell proliferation, migration and invasion of A375 and A875 MM cell lines. In addition, inhibition of nuclear factor-κB (NF-κB) attenuated LL-37-induced YB-1 expression. These results demonstrate that, through the upregulation of YB-1 expression and the activation of the NF-κB signaling pathway, LL-37 may promote the malignant progression of MM cells in vitro.

Antimicrobial peptide LL-37 promotes the proliferation and invasion of skin squamous cell carcinoma by upregulating DNA-binding protein A

The antimicrobial peptide LL-37 not only contributes to the host defence against microbial invasion but also regulates immune activity, angiogenesis and cell proliferation. Studies have shown that LL-37 participates in the development of a variety of tumours, such as lung cancer, ovarian cancer, breast cancer and melanoma. However, the role of LL-37 in the development of skin squamous cell carcinoma (SCC) is not clear. The present study used immunohistochemistry to confirm that the expression of human DNA-binding protein A (dbpA) was increased in SCC tissues. After stimulating SCC A341 cells, LL-37 was shown promote the proliferation, migration and invasion of these malignant cells. LL-37 also promoted the upregulation of dbpA mRNA and protein expression. In addition, after using small interfering RNA to silence the normal dbpA expression in these malignant cells, the proliferation and invasion of the tumor cells were significantly reduced. When the NF-κB inhibitor PDTC was used to inhibit the process of LL-37-stimulated cells, it was found that the original upregulated expression of dbpA was downregulated. Overall, the present demonstrated that by upregulating the expression of dbpA, LL-37 can promote the proliferation and invasion of tumour cells, and that this process depends on the NF-κB signalling pathway.

Primary cutaneous diffuse large B cell lymphoma-other successfully treated by the combination of R-CHOP chemotherapy and surgery: A case report and review of literature.

Rationale: The occurrence of primary cutaneous diffuse large B cell lymphoma-other (PCDLBCL-O) has been rarely reported in the literature. Its diagnosis is based on histopathological and immunohistochemical examinations. To improve the clinical diagnosis and treatment for PCDLBCL-O, we report a case of PCDLBCL-O successfully treated by the combination of R-CHOP (A chemotherapy protocol consists of cyclophosphamide, doxorubicin, vincristine, prednisone plus Rituximab) chemotherapy and surgery. The clinical manifestations, pathological characteristics, treatment and prognosis of the case were analyzed. Patient concerns: The patient was a 56-year-old female, presenting with red plaques and nodules in her left breast for 6 months. Diagnoses: Based on the clinical manifestation, histopathological and immunohistochemical results, the patient was diagnosed with PCDLBCL-O. Interventions: She was treated with 6 courses of R-CHOP chemotherapy combined with surgical resection. Outcomes: In the present case, fairly good curative effect was appeared with no recurrence within the 3 years’ follow-up. Lessons: Primary cutaneous diffuse large B cell lymphoma commonly occurs on the legs (leg type), rarely on other sites of the body. The clinical manefestations are so variant that its diagnosis depends on histopathological and immunohistochemical examinations. Like systemic diffuse large B cell lymphoma, patients should be treated with systemic chemotherapy.

An unusual case of multiple cutaneous Rosai‐Dorfman disease involving two separate parts of the body

Rosai-Dorfman disease (RDD), also called sinus histiocytosis with massive lymphadenopathy (SHML), is a rare benign histiocytosis characterized by histiocytic proliferation with enlarged lymph nodes. Approximately 40% of RDD patients have extranodal involvement, and skin is the most frequently affected organ. Only 3% of RDD patients have skin lesions exclusively, and this is called cutaneous RDD (CRDD). We report an unusual case of CRDD manifested as nodules of two distant parts.

Antimicrobial peptide LL-37 promotes the viability and invasion of skin squamous cell carcinoma by upregulating YB-1

Antimicrobial peptide LL-37 serves a function in the host defense against microbial invasion, and also regulates cell proliferation, immune activity and angiogenesis. Previous studies have reported that LL-37 participates in the development of numerous tumour types, such as ovarian cancer, lung cancer, melanoma and breast cancer. However, the function of LL-37 in the development of skin squamous cell carcinoma (SCC) has not yet been fully elucidated. The aim of the current study was to investigate how LL-37 promotes the expression of Y-box binding protein 1 (YB-1) in SCC. Short interfering RNA (siRNA) was used to inhibit the expression of YB-1, and in vitro MTT and Transwell migration assays were used to evaluate the effect of reduced YB-1 on the viability and invasion of A431 cells. A431 cells were stimulated with LL-37, and quantitative polymerase chain reaction, immunofluorescence and western blot analyses were used to detect changes in YB-1 expression. Mitogen-activated protein kinase kinase, mitogen-activated protein kinase and nuclear factor (NF)-κB signaling pathway inhibitors were also used to evaluate the mechanism of LL-37-induced YB-1 protein expression. It was found that YB-1 expression was increased in SCC tissue compared with normal tissue. Inhibiting YB-1 expression using siRNA significantly reduced the viability and suppressed the invasion of tumour cells (P<0.05 for both). LL-37 treatment at 0.05 µg/ml for 24 or 48 h significantly promoted YB-1 protein expression (P<0.05), and this was dependent on the NF-κB signaling pathway. In conclusion, the current study demonstrated that by upregulating the expression of YB-1, LL-37 can promote the occurrence and development of SCC, and this process involves the NF-κB signaling pathway.