TOX: a potential new immune checkpoint in cancers by pancancer analysis.

BACKGROUND: Thymocyte selection-associated HMG-BOX (TOX) belongs to a family of transcription factors containing a highly conserved region of the high mobility group box (HMG-Box). A growing body of research has shown that TOX is involved in the occurrence and development of tumors and promotes T-cell exhaustion. We assessed the role of TOX with The Cancer Genome Atlas (TCGA) Pancancer Data. METHODS: TOX expression was examined with RNA-seq data from the TCGA and Genotype-Tissue Expression (GTEx) databases. The genetic alteration status and protein level of TOX were analyzed using databases, including the Human Protein Atlas (HPA), GeneCards, and STRING. The prognostic significance was estimated with survival data from the TCGA. Moreover, R software was used for enrichment analysis of TOX. The relationship between TOX and immune cell infiltration was assessed with the Tumor Immune Estimation Resource (TIMER) 2.0 database and the "CIBERSORT" method. The correlation between TOX and immune checkpoints was further explored. Immunohistochemical analysis was used to further verify the difference in TOX expression between cancerous and paracancerous tissues, and cell viability was evaluated using a CCK-8 assay. RESULTS: In most cancer types in the TCGA cohort, differential TOX expression was observed. The genetic alteration status and protein level of TOX were examined, and the prognosis of cancers was associated with TOX expression. Moreover, TOX levels were closely related to different immune-related pathways, immune cell infiltration and immune checkpoints. Additionally, significant differences in TOX expression between several cancerous and paracancerous tissues were validated. Furthermore, TOX clearly impacted the viability of cancer cells. CONCLUSIONS: TOX, a potential biomarker for cancer, may be involved in the regulation of the immune microenvironment and can be used for new targeted drugs.

Matrine: A Promising Treatment for Ulcerative Colitis by Targeting the HMGB1/NLRP3/Caspase-1 Pathway.

BACKGROUND: Previous studies have found that matrine (MAT) effectively treated Ulcerative Colitis (UC). The purpose of this study is to explore its mechanism based on the HMGB1/NLRP3/Caspase-1 signaling pathway. METHODS: MAT was administered intragastrically to DSS-induced UC mice for 14 days. The Disease Activity Index (DAI) and histological staining were measured to detect histopathological changes in colon. The levels of IL-1ß, IL-6, and TNF-α in serum were measured by ELISA. The protein and mRNA expression of HMGB1/NLRP3/Caspase-1 in the colon were detected by immunohistochemistry, western Blotting or qRT-PCR. RESULTS: MAT improved the histological pathological changes of UC mice, as assessed by DAI, colonic length, and colonic mucosal injury. MAT also reduced colonic inflammatory damage by reducing the serum IL-1ß, IL-6, and TNF-α content and decreasing the expression of HMGB1, NLRP3, Caspase-1, and IL-1ß and proteins and mRNA in the colon. CONCLUSION: MAT could significantly alleviate DSS-induced UC symptoms by reducing the expressions of pro-inflammatory cytokines, such as IL-1ß, TNF-α, and IL-6, the mechanism of which is related to the inhibition of HMGB1/NLRP3/Caspase-1 signaling pathway.

CPT, the main test method of skin neuronal sensitivity.

BACKGROUND: Many scholars concentrate on skin barrier disruption of sensitive skin, but few focus on its increased neuronal sensitivity. OBJECTIVE: To study the possibility of using current perception threshold (CPT) measurement for the quantitative evaluation of skin neuronal sensitivity combined with stinging test. METHODS: The amount of 50 µL 10% lactic acid was applied on each side of the nasolabial fold at random. Subjects assessed stinging based on a 4-point scale at 30 s, 2.5 min and 5.0 min. CPT and transepidermal water loss (TEWL) were measured before and after stinging test. Subjects were divided into different groups based on their response to lactic acid. RESULTS: There was a positive correlation between CPTbefore and the sum of clinical scores (CSs). While the beginning time of stinging (BT) was shortened, the CPTbefore decreased and TEWL increased. CONCLUSION: Different degrees of skin susceptibility can be reflected by BT. CPT can be useful for the quantitative evaluation of skin neuronal sensitivity.

Acute skin barrier disruption with repeated tape stripping: an in vivo model for damage skin barrier.

PURPOSE: To establish a model of standardized acute barrier disruption, investigate the response of normal human to repeated tape stripping, and analyze the change of damaged skin with non-invasive examination techniques for skin, such as TEWL and squamometry. METHODS: Repeated tape stripping with corneofix was applied on three different anatomical sites; the measurement of TEWL was performed on the baseline and after every 5 strips. Then, the samples of corneofix were analyzed using Visioscan VC98 and squamometry. RESULTS: The parameter of TEWL and cohesion score show stable change trend. TEWL increased with frequency of stripping and were significantly higher compared with that of baseline on three sites. The results of staining of corneofix showed that the intercorneocyte cohesion is increased with the number of strips, and the more the number of strips, the more the fixation of dye per cell. CONCLUSION: The changes in the skin barrier function of different sites were different after it accepted physical stimulation, the process of damaging skin barrier could be divided into three stages based on the △TEWL. In addition, through stripping the skin of an adult, the in vivo model of damaged skin barrier could be setup.