Calcium-sensing receptor and NF-κB pathways in TN breast cancer contribute to cancer-induced cardiomyocyte damage via activating neutrophil extracellular traps formation.

Cardiovascular disorders are commonly prevalent in cancer patients, yet the mechanistic link between them remains poorly understood. Because neutrophil extracellular traps (NETs) have implications not just in cardiovascular diseases (CVD), but also in breast cancer (BC), it was hypothesized to contribute to CVD in the context of oncogenesis. We established a mouse model using nude mice to simulate liver metastasis of triple-negative BC (TNBC) through the injection of MDA-MB-231 cells. Multiple imaging and analysis techniques were employed to assess the cardiac function and structure, including echocardiography, HE staining, Masson staining, and transmission electron microscopy (TEM). MDA-MB-231 cells underwent treatment with a CaSR inhibitor, CaSR agonist, and NF-κB channel blocker. The phosphorylation of NF-κB channel protein p65 and the expression and secretion of IL-8 were assessed using qRT-PCR, Western Blot, and ELISA, respectively. In addition, MDA-MB-231 cells were co-cultured with polymorphonuclear neutrophils (PMN) under varying conditions. The co-localization of PMN extracellular myeloperoxidase (MPO) and DNA were observed by cellular immunofluorescence staining to identify the formation of NETs. Then, the cardiomyocytes were co-cultured with the above medium that contains NETs or not, respectively; the effects of NETs on cardiomyocytes apoptosis were perceived by flow cytometry. The ultrastructural changes of myocardial cells were perceived by TEM, and ELISA detected the levels of myocardial enzyme (LDH, MDA and SOD). Overall, according to our research, CaSR has been found to have a regulatory role in IL-8 secretion in MDA-MB-231 cells, as well as in the formation of NETs by PMN cells. These findings suggest CaSR-mediated stimulation in PMN can lead to increased NETs formation and subsequently to cytotoxicity in cardiomyocytes, which potentially via activation of the NF-κB signaling cascade of BC cell.

Nail changes in pemphigus and bullous pemphigoid: A single-center study in China.

Common autoimmune bullous diseases (AIBDs) include pemphigus and bullous pemphigoid (BP), which are primarily caused by IgG autoantibodies against the structural proteins of desmosomes at the cell-cell junction and hemidesmosomes at the epidermal-dermal junction. Few studies have assessed nail changes in patients with pemphigus or BP. In the present study, we collected the clinical data of 191 patients with AIBDs (108 patients with pemphigus and 83 patients with BP) and 200 control subjects. Nail changes were observed in 77.0% (147/191), 77.8% (84/108), and 75.9% (63/83) of patients with AIBDs, pemphigus, and BP, respectively, and 14.5% (29/200) of control subjects. Beau's lines and paronychia were the most common nail involvement, observed in 22.5% (43/191) and 22.5% (43/191) of patients with AIBDs, 25.0% (27/108) and 25.9% (28/108) of patients with pemphigus, 19.3% (16/83) and 18.1% (15/83) of patients with BP, respectively. The autoimmune bullous skin disorder intensity score (ABSIS) and the onset time of patients with pemphigus or BP with nail changes were different. Onychomycosis accounted for 21.5% (41/191) of all patients with AIBDs. The ABSIS was correlated with nail involvement in patients with BP (r = 0.46, p < 0.001), and weakly correlated with nail involvement in patients with AIBDs (r = 0.37, p < 0.001), pemphigus (r = 0.29, p = 0.009), and pemphigus vulgaris (PV; r = 0.35, p = 0.008). No correlation was observed between nail involvement and disease antibody titers. In conclusion, nail changes are frequently observed in patients with pemphigus and BP. The type and onset time of nail changes may indicate the severity of pemphigus and BP, which warrants the attention of dermatologists.

Rodlike YMn2O5 Powders Derived from Hydrothermal Process Using Oxygen as Oxidant.

A facile approach is proposed herein to fabricate YMn2O5 powders with the hydrothermal method with oxygen as an oxidant. The structure and morphology of the as-synthesized YMn2O5 powders were characterized by XRD, SEM, and high-resolution transmission electron microscopy (HRTEM). The results manifested that the main factors that affected the formation of the rod-like YMn2O5 structures were the stirring time, hydrothermal temperature, and hydrothermal time. The oxidation time in the air had a remarkable effect on the final product by oxidizing Mn2+ ions to Mn3+ ions and Mn4+ ions. The obtained YMn2O5 powder was single crystalline and possessed a nanorod morphology, where the growth direction was along the c axis. The possible formation mechanism involved a dissolution-crystallization mechanism. Under the 397 nm excitation, the Mn4+ ions exhibited an intense orange emission at 596 nm. The energy bandgap of YMn2O5 powders was 1.18 eV.

Analysis of POFUT1 gene mutation in a Chinese family with Dowling-Degos disease.

Dowling-Degos disease (DDD) is an autosomal dominant genodermatosis characterized by reticular pigmented anomaly mainly affecting flexures. Though KRT5 has been identified to be the causal gene of DDD, the heterogeneity of this disease was displayed: for example, POFUT1 and POGLUT1 were recently identified and confirmed to be additional pathogenic genes of DDD. To identify other DDD causative genes, we performed genome-wide linkage and exome sequencing analyses in a multiplex Chinese DDD family, in which the KRT5 mutation was absent. Only a novel 1-bp deletion (c.246+5delG) in POFUT1 was found. No other novel mutation or this deletion was detected in POFUT1 in a second DDD family and a sporadic DDD case by Sanger Sequencing. The result shows the genetic-heterogeneity and complexity of DDD and will contribute to the further understanding of DDD genotype/phenotype correlations and to the pathogenesis of this disease.

Nasal cutaneous infection in a healthy boy caused by Fusarium moniliforme.

A healthy 10-year-old Chinese boy developed verrucous plaques on the nose. The fungus was identified as Fusarium moniliforme via culture of biopsy fragments. The patient had normal immune status and was successfully treated with oral itraconazole (100 mg/day) for 2 months and application of oral itraconazole and topical sertaconazole nitrate cream. Fusarium is a ubiquitous hyalohyphomycete isolated from food that is also widespread in the environment and is present at all latitudes. Infections due to this mold may be disseminated or localized. Fusarium species have been known to colonize the cornea, nails, and burn eschars in otherwise healthy patients. Cutaneous and disseminated infections have been reported mostly in immunocompromised hosts. Here we describe an unusual case of localized infection caused by Fusarium moniliforme in an otherwise healthy child, with significant improvement after 2 months of oral itraconazole and topical sertaconazole nitrate cream therapy.

Evaluation of the combination of BP180-NC16a enzyme-linked immunosorbent assay and BP230 enzyme-linked immunosorbent assay in the diagnosis of bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is an acquired autoimmune subepidermal blistering disease characterized by circulating IgG autoantibodies directed against BP180 and BP230 hemidesmosomal proteins. Previous studies have demonstrated that antibodies against the NC16a domain of BP180 mediate BP pathogenesis, while antibodies against BP230 enhance the inflammatory response. Recently, commercial BP180-NC16a enzyme-linked immunosorbent assay (ELISA) and BP230 ELISA kits were developed to detect anti-BP180 and anti-BP230 autoantibodies in human BP sera. AIMS: To evaluate the efficacy of BP180-NC16a ELISA and BP230 ELISA in the initial diagnosis of BP. METHODS: Sera from 62 BP patients and 62 control subjects were tested by BP180-NC16a ELISA and BP230 ELISA and compared with findings from indirect immunofluorescence (IIF) and immunoblotting (IB) to determine the sensitivity and specificity of these assays. RESULTS: The sensitivities of BP180-NC16a ELISA and BP230 ELISA were 87.1% (54/62) and 56.5% (35/62), respectively, and the specificities of both were 100% (62/62). Using both ELISAs for diagnosis increased the sensitivity to 95.2% (59/62) and was statistically comparable with IB sensitivity. CONCLUSIONS: ELISA is a convenient, effective, and reliable method for serodiagnosis of BP, and combined use of BP180-NC16a ELISA and BP230 ELISA can increase the sensitivity of this diagnostic approach.

Accuracy of indirect immunofluorescence on sodium chloride-split skin in the differential diagnosis of bullous pemphigoid and epidermolysis bullosa acquisita.

BACKGROUND: Previous reports have shown that indirect immunofluorescence (IIF) performed on sodium chloride-split skin (SSS) is helpful to differentiate epidermolysis bullosa acquisita (EBA) from bullous pemphigoid (BP). Antibodies of BP may bind to the epidermal side of SSS, while antibodies of EBA bind to the dermal side. AIMS: To determine the accuracy of IIF-SSS in the differential diagnosis of EBA and BP utilizing immunoblotting (IB) analysis. METHODS: Sera from 78 patients, diagnosed with BP by clinical features, histopathology, and direct immunofluorescence (DIF), were assayed using IIF-SSS and IB. RESULTS: Of the 43 serum samples with an epidermal reaction to IIF-SSS assay, 42 were recognized with BP antigens (180 kDa or 230 kDa). Of the 11 serum samples with a dermal reaction pattern, 7 were recognized with the 290 kDa antigen of EBA and 3 with sera bound BP antigens. Seven serum samples with epidermal and dermal combined staining, of which 5 of them reacted with BP antigens, 1 reacted with both BP and EBA antigens. One serum sample from each group showed a negative result by IB. Approximately 9.0% (7/78) of patients diagnosed with BP using regular methods were actually EBA. CONCLUSIONS: Epidermal reaction using the IIF-SSS assay highly correlated with the diagnosis of BP. However, dermal reactions correlated poorly with EBA, with some serum samples from BP patients binding to dermal-side antigens. In both epidermal and dermal stained sera using IIF-SSS, there was a possibility of BP and EBA. Differential diagnosis should be confirmed using IB, especially in cases of dermal and double staining patterns assayed using IIF-SSS.

Histological classification of melasma with reflectance confocal microscopy: a pilot study in Chinese patients.

OBJECTIVE: To investigate the histological classification of melasma with reflectance confocal microscopy (RCM) in vivo. METHODS: Two hundred and ten cases with facial melasma lesions were enrolled. After informed consent, the target melasma lesion of 10 patients were imaged with RCM and then biopsied as well. Under the RCM scanning, the distribution of the melanin determined the histological types, and then, the results of RCM images were compared with those of the histopathology. The other 200 cases were tested only with RCM. RESULTS: For the 10 cases imaged and biopsied, compared with that of the perilesional normal skin, the amount of melanin was significantly increased in the epidermis in all lesions under RCM, while three cases also found melanin in the dermis. Thus, seven of the 10 patients were categorized as the epidermal type while the other three as mixed ones, and the results were well correlated with those of the histopathology. Of the other 200 patients, 143 cases 71.5%) were categorized as the epidermal type while the other 57 (28.5%) cases as mixed ones. LIMITATIONS: If more melasma cases are biopsied, the data will be more convincing. CONCLUSION: RCM in vivo analysis shows complete coherence with histopathology results, which could be an alternative for the classification of melasma, and based on the results of RCM imaging, melasma is classified into two major types: the epidermal type and mixed type.

Seborrheic keratosis or verruca plana? A pilot study with confocal laser scanning microscopy.

BACKGROUND: Differentiation of some seborrheic keratosis (SK) and verruca plana (VP) lesions is a challenge. Confocal laser scanning microscopy (CLSM) has been proved to be useful in the diagnosis of skin diseases; however, to date, there is no report on the differential study of the two diseases with CLSM. OBJECTIVES: To obtain the CLSM image characteristics of SK and VP, and then test the differential ability of CLSM imaging. METHODS: We recruited 10 patients with typical lesions of SK under CLSM images to validate the features reported. Another 10 patients with typical VP lesions were also recruited, imaged with CLSM and biopsied to obtain the features under CLSM images based on histology analysis. Then, we attempt to summarize and refine those characteristics collected to obtain the most significant ones. All the cases with lesions suggestive of SK or VP were advised to undergo imaging with CLSM, and if CLSM imaging reflected discordantly with the clinical diagnosis, a biopsy was suggested for the exact lesion imaged. Those cases with CLSM and histology results were collected. Finally, two clinical dermatologists, who had no previous experience with CLSM, were tested with the simplified features of CLSM images to differentiate the suspected lesions of SK and VP among the cases collected. RESULTS: In total, there were 58 cases with CLSM images and histology results collected, in which, 40 cases were diagnosed as SK and 18 cases as VP by histology. The two blinded dermatologists' judgments were identical to histology analysis. CONCLUSION: CLSM proved to be valuable in the differential diagnosis of SK and VP. The simplified characteristics were easily understood and acceptable to those with no previous experience of CLSM.