Serum lipids may causally affect the occurrence of alopecia areata: A Mendelian randomization study.

PURPOSE: The etiology of alopecia areata (AA) in relation to serum lipids remains unclear, thereby prompting our intention to do Mendelian study on this subject. DESIGN: Two-sample Mendelian randomization (MR) analysis was performed in the study. The inverse variance-weighted method was used as the primary method. METHODS: In our study, we integrated a set of 123 single-nucleotide polymorphisms (SNPs) into our analysis. These SNPs have been extensively studied and are known to exhibit associations with serum lipids. We sourced these SNPs from a variety of relevant studies and consortia that specifically focus on lipid-related research, such as the MRC Integrative Epidemiology Unit. These carefully curated SNPs were then utilized as instrumental variables in our analysis, allowing us to explore and evaluate the causal relationships between these genetic variants and serum lipids. By incorporating this comprehensive set of SNPs, we aimed to enhance the precision and robustness of our findings, shedding light on the intricate interplay between genetics and serum lipids. RESULTS: In the MR analysis, a higher total lipid concentration in large low-density lipoprotein (LDL) particles (odds ratio [OR] = 1.502; 95% confidence interval [CI] = 1.086-1.953; p = 0.006), a greater ratio of cholesteryl esters to total lipids in chylomicrons and extremely large very LDL (VLDL) particles (OR = 2.174; 95% CI = 1.300-2.500; p = 0.010), and a greater ratio of cholesterol to total lipids in chylomicrons and extremely large VLDL particles (OR = 2.363;95% CI = 1.556-4.438; p = 0.004), were genetically predicted to be causally associated with an increased risk of AA, while patients with a higher triglyceride to total lipids ratio in chylomicrons and extremely large VLDL particles had a lower risk of AA (OR = 0.481; 95% CI = 0.191-1.270; p = 0.002). CONCLUSION: This study found that serum lipids may be causally implicated in AA.

Tacrolimus reverses pemphigus vulgaris serum-induced depletion of desmoglein in HaCaT cells via inhibition of heat shock protein 27 phosphorylation.

BACKGROUND: Glucocorticoids are the first-line treatment for Pemphigus vulgaris (PV), but its serious side effects can be life-threatening for PV patients. Tacrolimus (FK506) has been reported to have an adjuvant treatment effect against PV. However, the mechanism underlying the inhibitory effect of FK506 on PV-IgG-induced acantholysis is unclear. OBJECTIVE: The objective of this study was to explore the effect of FK506 on desmoglein (Dsg) expression and cell adhesion in an immortalized human keratinocyte cell line (HaCaT cells) stimulated with PV sera. METHODS: A cell culture model of PV was established by stimulating HaCaT cells with 5% PV sera with or without FK506 and clobetasol propionate (CP) treatment. The effects of PV sera on intercellular junctions and protein levels of p38 mitogen-activated protein kinase (p38MAPK), heat shock protein 27 (HSP27), and Dsg were assayed using western blot analysis, immunofluorescence staining, and a keratinocyte dissociation assay. RESULTS: PV sera-induced downregulation of Dsg3 was observed in HaCaT cells and was blocked by FK506 and/or CP. Immunofluorescence staining revealed that linear deposits of Dsg3 on the surface of HaCaT cells in the PV sera group disappeared and were replaced by granular and agglomerated fluorescent particles on the cell surface; however, this effect was reversed by FK506 and/or CP treatment. Furthermore, cell dissociation assays showed that FK506 alone or in combination with CP increased cell adhesion in HaCaT cells and ameliorated loss of cell adhesion induced by PV sera. Additionally, FK506 noticeably decreased the PV serum-induced phosphorylation of HSP 27, but had no effect on p38MAPK phosphorylation. CONCLUSION: FK506 reverses PV-IgG induced-Dsg depletion and desmosomal dissociation in HaCaT cells, and this effect may be obtained by inhibiting HSP27 phosphorylation.

Specific labeling and identification of bacteria based on concentration-dependent carbon dot staining combined with hyperspectral imaging.

Concentration-dependent carbon dot (CD) fluorescence was developed and utilized alongside hyperspectral microscopy as a specific labeling and identification technique for bacteria. Staining revealed that the CD concentration within cells depended on the characteristic intracellular environment of the species. Therefore, based on the concentration dependence of the CD fluorescence, different bacterial species were specifically labeled. Hyperspectral microscopy captured subtle fluorescence variations to identify bacteria. Method validation using Bacillus subtilis and Bacillus licheniformis succeeded with an identification accuracy of 99%. As a simple, rapid method for labeling and identifying bacterial species in mixtures, this technique has excellent potential for bacterial community studies.

Identification of DAPI-stained normal, inflammatory, and carcinoma hepatic cells based on hyperspectral microscopy.

Gross chromatin imbalance and high DNA content are distinct features of various types of cancer cells. However, severe inflammation can also produce similar symptoms in cells. In this study, normal, inflammatory, and carcinoma hepatic cells were stained with 4',6-diamidino-2-phenylindole (DAPI) and investigated by hyperspectral microscopy. DAPI is a DNA-sensitive fluorochrome. Therefore, the differences in the cellular DNA of the samples can be revealed by the corresponding fluorescence. Our experimental results demonstrate that although chromosomal disorder and high DNA content both occur in severely inflammatory and carcinoma hepatic cells, there is still a slight difference in their DNA, making their fluorescent intensity and even their spectral shapes distinguishable. Based on these spectral features, we developed a method for the precise identification of normal, inflammatory, and carcinoma hepatic cells in the field of view. The identification accuracy for these three types of cells was 99.8%. We believe that examination that combines DAPI staining with hyperspectral microscopy is a potential method for the identification and investigation of various types of cancer tissues.

Hypochlorous acid initiated lipid chlorination at air-water interface.

There has been a surge of interest in interfacial hypochlorous acid (HOCl) chemistry for indoor air quality and public health. Here we combined nanoelectrospray mass spectrometry (nESI-MS) and acoustic levitation (AL) techniques to study the chlorination chemistry of three model lipids (DPPE, POPG, DOPG) mediated by HOCl at the air-water interface of levitated water droplet. For DPPE with no CC double bonds, HOCl was insensitive to the alkane chains, and showed considerable delay directing to head amino groups compared to that in aqueous environment. Chlorination chemistry, for POPG and DOPG with CC double bonds, preferentially reacted with double bonds of one chain. The mechanism was discussed in light of these observations, and it is concluded that the increased hydrophilicity of the chlorinated chain disturbed the lipid packing and attracted it toward the water phase. In addition, the reaction rate constant and reactive uptake coefficient suggested that the chlorination of lipids exposed to HOCl at the air-water interface is likely to occur rapidly. These results gain the knowledge of HOCl mediated lipid interface reaction at the molecule level, and would better understand the adverse health effects associated with elevated indoor pollutants.

Hyperspectral microscopy combined with DAPI staining for the identification of hepatic carcinoma cells.

In this study, the DAPI staining is firstly reported for use in the identification of hepatic carcinoma cells based on hyperspectral microscopy. Nuclei in cancer cells usually contain more aneuploidies than that in normal cells, leading to the change of DNA content. Here, we stain hepatic carcinoma tissues and normal hepatic tissues with 4',6-diamidino-2-phenylindole (DAPI) which is sensitive to the DNA content as a fluorochrome binds to DNA. Consequently, the difference in DNA content between hepatic carcinoma cells and normal hepatic cells can be identified by the fluorescent spectral characteristics. Harnessing the hyperspectral microscopy, we find that the fluorescent properties of these two kinds of cells are different not only in the intensity but also in the spectral shape. These properties are exploited to train a support vector machine (SVM) model for classifying cells. The results show that the sensitivity and specificity for the identification of 1000 hepatic carcinoma samples are 99.3% and 99.1%, respectively.

Photodynamic therapy for keratoacanthoma on the upper lip.

BACKGROUND: Keratoacanthoma (KA) is a cutaneous neoplasm, which is similar to squamous cell carcinoma (SCC) clinically, cytologically, and histopathologically. Surgical resection is the first choice for treating KA, but it may be impractical when a KA is located in a cosmetically sensitive area. OBSERVATION: We describe a patient with a nodule on the right upper lip. We performed a surgical biopsy to obtain a histopathological diagnosis. Specimen analysis revealed a diagnosis of KA. As the tumor was located in the upper lip, a direct resection may require a flap to reconstruct the lip shape; instead, a noninvasive field approach using photodynamic therapy (PDT) was initiated. After five sessions of treatment, the lesion disappeared, and there was no scar. CONCLUSIONS: Although there is no consensus on using PDT to treat KA, we provide a case report on the effective use of PDT in the treatment of KAs. PDT can be an alternative treatment option when KA is located in a particular anatomic site.

Dual-type hyperspectral microscopic imaging for the identification and analysis of intestinal fungi.

A method based on a dual-type (transmission and fluorescence) hyperspectral microscopic image system was developed to identify species of intestinal fungi. Living fungi are difficult to identify via transmission spectra or fluorescence spectra alone. We propose an identification method based on both fluorescence and transmission spectra that employs a series of image processing methods. Three species of intestinal fungi were used to evaluate the method. The results demonstrate that the specificity of the model trained with dual-type spectra was 98.36%, whereas the specificities achieved by training with fluorescence spectra and transmission spectra alone were 94.04% and 92.88%, respectively.