FANCI serve as a prognostic biomarker correlated with immune infiltrates in skin cutaneous melanoma.

Background: As a member of tumor, Skin cutaneous melanoma (SKCM) poses a serious threat to people's health because of its strong malignancy. Unfortunately, effective treatment methods for SKCM remain lacking. FANCI plays a vital role in the occurrence and metastasis of various tumor types. However, its regulatory role in SKCM is unclear. The purpose of this study was to explore the association of FANCI with SKCM. Methods: This study investigated the expression of FANCI in GSE46517, GSE15605, and GSE114445 from the Gene Expression Omnibus database and The Cancer Genome Atlas (TCGA)-SKCM datasets using the package "limma" or "DESeq2" in R environment and also investigated the prognostic significance of FANCI by utilizing the GEPIA database. Additionally, our research made use of real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical (IHC) staining to verify FANCI expression between SKCM and normal tissues and developed the knockdown of FANCI in A375 and A875 cells to further analyze the function of FANCI. Finally, this study analyzed the correlation of FANCI and tumor-infiltrating immune cells by CIBERSORT, ESTIMATE, and ssGSEA algorithms. Results: The FANCI level was increasing in SKCM tissues from GSE46517, GSE15605, GSE114445, and TCGA-SKCM. However, high FANCI expression correlated with poor overall survival. The RT-qPCR and IHC confirmed the accuracy of bioinformatics. Knocking down FANCI suppresses A375 and A875 cell proliferation, migration, and invasion. FANCI could be involved in the immunological milieu of SKCM by regulating immune responses and infiltrating numerous immune cells, particularly neutrophils, CD8+ T cells, and B cells. Furthermore, patients with SKCM who have a high FANCI expression level are reported to exhibit immunosuppression, whereas those with a low FANCI expression level are more likely to experience positive outcomes from immunotherapy. Conclusions: The increased FANCI expression in SKCM can be a prognostic biomarker. Knockdown FANCI can reduce the occurrence and progression of SKCM. The FANCI expression provides a foundation for predicting the immune status and treatment of SKCM.

Identification of IRF1 as a Novel Pyroptosis-Related Prognostic Biomarker of Atopic Dermatitis.

Purpose: The aim of this study was to characterize key biomarkers associated with pyroptosis in atopic dermatitis (AD). Materials and methods: To identify the differentially expressed pyroptosis-related genes (DEPRGs), the gene expression profiles GSE16161 and GSE32924 from the Gene Expression Omnibus (GEO) database were utilized. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to determine the potential biological functions and involved pathways. Furthermore, protein-protein interaction network analyses were performed to identify hub genes. The types and proportions of infiltrating immune cells were detected by immune filtration analysis using CIBERSORT. A 12-axis competing endogenous RNA (ceRNA) network was constructed utilizing the miRNet database. Immunohistochemistry (IHC) further validated the differential expression of a key gene IRF1 in the skin tissues collected from AD patients. The collection of skin tissue from human subjects in this study were reviewed and approved by the IRB of Yueyang Integrated Chinese and Western Medicine Hospital (KYSKSB2020-125). Results: The study identified a total of 76 DEPRGs, which were enriched in genes associated with the inflammatory response and immune regulation. There was a higher percentage of activated dendritic cells and a lower percentage of resting mast cells in AD samples. PVT1 expression was associated with upregulation of hub genes including CXCL8, IRF1, MKI67, and TP53 in the ceRNA network and was correlated with activated dendritic cells in AD. As a transcription factor, IRF1 could regulate the production of downstream inflammatory factors. The IHC study revealed that IRF1 was overexpressed in the skin tissues of AD patients, which were consistent with the results of the bioinformatic study. Conclusions: IRF1 and its related genes were identified as key pyroptosis-related biomarkers in AD, which is a crucial pathway in the pathogenesis of AD.

Activatable Fluorescence-Encoded Nanoprobes Enable Simple Multiplexed RNA Imaging in Live Cells.

Benefiting from superior programmable performance and flexible design of DNA technologies, a variety of single-molecule RNA fluorescence imaging methodologies have been reported. However, the multiplexing capability is restricted owing to the spectral overlap of fluorophores. To overcome this limitation, some inspiring multiplex imaging strategies have been developed, but in practice, it remains challenging to achieve convenient and rapid imaging in live cells due to complex designs and additional pretreatments to increase cell permeability. Here, we report an activatable fluorescence-encoded nanoprobe (AFENP) strategy, through which fluorescence-encoded functional modules for qualitative analysis and activated nucleic acid assemblies functional modules for quantitative testing enable simple multiplexed RNA imaging in single live cells. As a proof of principle, by two distinguishable fluorophores (fluorescein and rhodamine B) and their seven distinctly differentiated intensity levels, self-assembled AFENP enables simplified and quick simultaneous in situ detection and imaging of seven types of targets in live single cells because the fluorescent quantitative signal is activated only in the presence of target avoiding the washing procedures and additional pretreatment to increase cell permeability is undesired. We expect that this practical single-cell analysis platform will be adopted for multiple gene expression analysis and imaging in live cells on account of its simplicity and multiplex capability.

Effectiveness of traditional Chinese medicine preparations for facial seborrheic dermatitis: case reports.

Facial seborrheic dermatitis is a chronic skin condition that presents as erythematous scaly dermatitis and has a detrimental effect on the patient's quality of life. The purpose of this article is to present successful treatment of two male patients with face seborrheic dermatitis, one aged 50 and the other aged 56, who developed facial seborrheic dermatitis following facial erythema eruptions. We diagnosed it as face seborrheic dermatitis based on the patients' initial appearances and the location of the erythema during the episode. The previous doctor diagnosed the patients' facial symptoms as related to allergies or infections; therefore, they were treated with long-term anti-inflammatory (tacrolimus) and antiallergic medications (loratadine) throughout the disease's early stages. Erythema of the face was recurring and recalcitrant. Their facial skin lesions vanished after one week of Chinese herbal medicine treatment along with warming yang therapy. The application of the principle of warming the kidney yang to the treatment of face seborrheic dermatitis produced favorable results. This may be an advantageous adjunct to the treatment of recurrent seborrheic dermatitis of the face. High-performance liquid chromatography coupled with electrospray mass spectrometry (HPLC/ESI-MS) was used to determine the primary components of the Chinese herbal formula "adjusted Shen-Liu-Wei (ASLW)," which has six natural substances as its primary components. As a result, we believe that the Chinese herbal compound ASLW might be a viable alternative for symptom relief and successful treatment of face seborrheic dermatitis.

Phellopterin cream exerts an anti-inflammatory effect that facilitates diabetes-associated cutaneous wound healing via SIRT1.

BACKGROUND: Diabetic ulcers, which are characterized by chronic nonhealing wounds with a long-lasting inflammatory state, are a typical symptom in individuals with diabetes, and there is still no effective treatment for these lesions. Angelica dahurica plays a critical role in inflammatory diseases. Among numerous monomeric compounds, phellopterin has been shown to have anti-inflammatory properties. PURPOSE: To research the bioactive constituents in Angelica dahurica and their mechanism of action in treating diabetic ulcers. STUDY DESIGN: Chemical research of Angelica dahurica led to the identification of a new coumarin, dahuricoumarin A (1), along with seven known compounds (2 - 8). All compounds were tested for anti-inflammatory activity, and phellopterin, compound (3), significantly decreased the expression of intercellular cell adhesion molecule-1 (ICAM-1), a representative indicator of inflammation. Phellopterin can also increase SIRT1 protein, a key target for inflammation. In our research, we confirmed the anti-inflammatory effects of phellopterin on diabetic ulcers and explored the underlying mechanism of action. METHODS: The expression of IFN-γ, SIRT1, and ICAM-1 in human diabetic ulcer tissues was studied using immunohistochemistry. Streptozotocin was used to induce a diabetic model in C57BL/6J mice, and ulcers were surgically introduced. After phellopterin treatment, the skin lesions of diabetic mice were observed over a period of time. The protein and mRNA expression levels of SIRT1 and ICAM-1 were measured using H&E, qRT-PCR and immunohistochemical staining. A HaCaT cell inflammatory model was induced by IFN-γ. Using a lentiviral packaging technique, MTT assay, and Western blotting, the effect of phellopterin on the proliferation of HaCaT cells and the expression of ICAM-1 was evaluated under normal and SIRT1 knockdown conditions. RESULTS: High levels of ICAM-1 and IFN-γ were identified, but low levels of SIRT1 were found in human diabetic ulcer tissues, and phellopterin showed therapeutic benefits in the healing process by attenuating chronic inflammation and promoting re-epithelialization, along with SIRT1 upregulation and ICAM-1 downregulation. However, inhibiting SIRT1 reversed its proliferative and anti-inflammatory effects. CONCLUSION: In vitro and in vivo, phellopterin exerts anti-inflammatory and proliferative effects that promote diabetic wound healing, and the potential mechanism depends on SIRT1.

Residual Stress Redistribution Analysis in the Repair Welding of AA6082-T6 Aluminum Alloy Joints: Experiment and Simulation.

Residual stress has a three-dimensional scale effect (length, depth, and width) in the process of repair welding, which has a detrimental impact on the service of the aluminum alloy welded structures in high-speed trains. This paper aims to systematically analyze the effects of the repair welding dimension on the residual stress redistribution and obtain the optimal repair welding principles. A combination of blind-hole drilling method and stress linearization in BS7910 was adopted to investigate residual stress redistribution under various repair welding dimensions. The results indicate that repair welding dimension was in accordance with the principle of "SNL (shallow, narrow and long)" and the optimal repair length, depth, and width of butt joints in this study were 15t, 0.25t, and t, respectively (t is the plate thickness of butt joints).

A fluorescent, chirality-responsive, and water-soluble cage as a multifunctional molecular container for drug delivery.

In recent years, the rational design and construction of drug delivery systems (DDSs) via a supramolecular approach for improving chemical therapeutics have gained significant attention. Here, we report a host-guest DDS formed from a fluorescent, chirality-responsive, and water-soluble tetraphenylethene-based octacationic cage as a fluorescent/chiral probe, solubilizer, and molecular cargo, which can recognize chiral nucleoside drugs, enhance the solubility of insoluble drugs, and protect drugs from the outside environment by forming host-guest complexes in aqueous solution. Given the fluorescence properties and dynamically rotational conformation of tetraphenylethene (TPE) units, this fluorescent and chirality-responsive cage exhibits different responses including turn-on/turn-off fluorescence and negative/positive circular dichroism (CD) when binding with different chiral nucleoside drugs in water, resulting in multiple-responsive photophysical behaviors for these chiral drugs. Furthermore, this water-soluble cationic cage with a hydrophobic cavity can improve the water solubility of insoluble drugs (e.g., CPT) by forming host-guest complexes in water. More importantly, this multifunctional cage exhibits a low toxicity to both human colon and breast cancer cell lines in vitro, and drugs encapsulated by the cage are more effective in killing cancer cells than drugs alone. Finally, the on-off-on fluorescence responses in the formation and dissociation processes of the cage⊃drug complexes have been successfully used to monitor drug release and track drug delivery by fluorescence microscopy in vitro. Therefore, this fluorescent, chirality-responsive, and water-soluble cage as a multifunctional molecular container can be used to construct a smart drug delivery system with several functions of fluorescence and CD detection, water solubilization, real-time monitoring, and chemotherapy.

A Novel Cell-Assisted Enhanced Chemiluminescence Strategy for Rapid and Label-Free Detection of Tumor Cells in Whole Blood.

In this study, an interesting phenomenon was found where cells (including tumor and normal cells) managed to significantly enhance chemiluminescence (CL) signals. The possible reaction mechanism may be that cells can be severely damaged by CL substrates, and the released contents, possibly proteins (such as cytochrome c), can remarkably magnify CL owing to the increased production of singlet oxygen. More importantly, based on the above phenomena, a novel cell-assisted enhanced CL strategy was proposed for the rapid and label-free detection of tumor cells. The complexes of aptamer sgc8c and streptavidin-modified magnetic beads were employed to recognize and isolate target tumor cells from whole blood. The enhanced CL intensity, which was triggered directly by the captured cells, was measured. The proposed strategy exhibited a good detection performance with a linear range from 200 to 10,000 cells/mL. The analysis can be finished in ∼30 min, and the limit of detection was down to 100 cells/mL. The recoveries and relative standard deviations were 97.81-102.71% and 3.46-12.71%, respectively. Moreover, the established method can successfully distinguish the leukemia patients from healthy people. Therefore, it provides a novel, rapid, and simple method for the determination of tumor cells, which can be used in further practice.

Plasma miR-126 expression correlates with risk and severity of psoriasis and its high level at baseline predicts worse response to Tripterygium wilfordii Hook F in combination with acitretin.

BACKGROUND: Treatment of psoriasis is always difficult, which requires intensive scientific research. OBJECTIVE: Tripterygium wilfordii Hook F (TwHF) with acitretin(TwHF + acitretin) is normally used in treating psoriasis. This study aimed to investigate the correlation of plasma miR-126 expression with risk and severity of psoriasis, and its predictive value of response to TwHF + acitretin treatment in psoriasis. METHODS: MiRNA-126(MiR-126) expression in plasma was analyzed in psoriasis patients at month 0 (M0), M1, M3 and M6 and in health controls (HCs) at enrollment by qPCR. Psoriasis-affected body surface area (BSA) and Psoriasis Area and Severity Index (PASI) score were used to assess severity and treatment response. RESULTS: Plasma miR-126 levels were decreased in psoriasis patients compared with HCs (P < 0.001), with area under the curve (AUC) of 0.771. MiR-126 expression was negatively correlated with PASI score (P = 0.001), and negatively associated with psoriasis-affected BSA (P = 0.825). At M6, 65.3% and 36.1% patients achieved PASI 50 and 75, respectively. MiR-126 increased at M1, M3 and M6 after TwHF + acitretin treatment when comparing with M0 (all P < 0.001). Meanwhile, miR-126 expression baseline in PASI 50 group declined when comparing with non-PASI 50 group (P < 0.001). Additionally, data revealed that the cause of high miR-126 baseline level was due to unsuccessfully achieving PASI 50 at M6 after TwHF + acitretin treatment (P < 0.001). However, miR-126 baseline expression was not a predictive factor for PASI 75 achievement (P > 0.05). CONCLUSION: Plasma miR-126 expression is negatively correlated with psoriasis risk and severity, and its high baseline level can be used as a biomarker to predict worse clinical response to TwHF + acitretin treatment in psoriasis.

Depression Symptoms Predict Worse Clinical Response to Etanercept Treatment in Psoriasis Patients.

BACKGROUND/AIMS: This study aimed to investigate the predicting values of depression and anxiety symptoms for clinical response to etanercept treatment in psoriasis patients. METHODS: A total of 85 psoriasis patients who received 6 months of etanercept treatment were consecutively enrolled in this prospective cohort study. The Psoriasis Area and Severity Index (PASI) score was evaluated at month 0 (M0), M1, M3, and M6, and the corresponding PASI 75/90 response at each visit was assessed. Also, anxiety and depression symptoms were assessed by the Hospital Anxiety and Depression Scale (HADS) at M0, M1, M3, and M6. RESULTS: Depression symptoms were observed to correlate with female gender (p = 0.004), longer disease duration (p = 0.018), and higher PASI score (p < 0.001), and anxiety symptoms were seen to be associated with female gender (p = 0.017), larger psoriasis-affected body surface area (p = 0.049), and higher PASI score (p = 0.017) in psoriasis patients. After etanercept treatment, HADS-Depression (HADS-D) and HADS-Anxiety (HADS-A) scores were both decreased at M1, M3, and M6 (all p < 0.001) compared with M0. Most importantly, baseline depressed patients presented with a lower PASI 75 response rate at M3 (p = 0.014) and M6 (p = 0.005), and a reduced PASI 90 response rate at M6 (p = 0.045) compared with baseline non-depressed patients. Furthermore, multivariate logistic regression analyses revealed that depression symptoms at baseline were an independent predictive factor for the lower possibility of both PASI 75 response (p = 0.048) and PASI 90 response (p = 0.048) achievements at M6 in psoriasis patients. However, no correlation of baseline anxiety symptoms with PASI 75/90 responses was observed. CONCLUSION: Depression symptoms at baseline independently predict a worse clinical response to etanercept treatment in psoriasis patients.