The action of glycyrol on acute inflammation <i>in vivo.</i>

<p>Acetic acid-induced capillary permeability test. Mice were given 150 mg/kg glycyrol perorally for 5 consecutive days before the acute inflammatory test. 0.5% Evan's blue was injected into the tail vein 30 min after the last peroral administration. Permeability scored by Evans Blue concentration in peritoneal fluid (light absorbance at 590 nm). Columns represent means ±SD from 8 mice. Differences between groups were tested by Student's t-test. *P<0.05 for comparison with Model group.</p

Effect of the peroral administration of glycyrol on immunoregulation <i>in vivo.</i>

<p>DNFB-induced DTH reaction (panel A) and carbon particle clearance test (panel B) conducted on mice given glycyrol (50 or 100 mg/kg) or CsA (50 mg/kg). The mice were initially sensitized by 50 µL of 1% DNFB on abdomens 30 min after drug administration on days 1 and 2. On day 5, 30 min after drug administration, mice were treated with 10 µL of 1% DNFB on both sides of their right ear. The mice were killed by cervical dislocation 24 h after the third sensitization. A1: ear swelling; A2: thymus; A3: spleen; B: phagocytic index. Data are shown as means ±SD from 8 mice. Differences between groups were tested by Student's t-test. # P<0.05 for comparison with Vehicle group, *P<0.05 for comparison with Model group.</p

Glycyrol inhibits expression of p-IκB and NF-κB.

<p>A & B: Jurkat cells were stimulated with PMA plus Ion or a combination of indicated concentrations glycyrol or CsA and PMA plus Ion for 24 h to induce IκB-α expression. A: Western blot picture of p-IκB-α; B: Quantification of Western blot. C: RAW 264.7 cells were induced with PMA plus Ion or a combination of indicated concentrations glycyrol or CsA and PMA plus Ion for 24 h to induce NF-κB expression, and measured by dual-reporter gene assay system. Assays were performed in triplicate. Data represent means ±SD over three independent experiments. # P<0.05 for comparison with naïve group, *P<0.05 for comparison with PMA plus Ion-stimulated group.</p

DataSheet_1_Immune landscape and risk prediction based on pyroptosis-related molecular subtypes in triple-negative breast cancer.zip

The survival outcome of triple-negative breast cancer (TNBC) remains poor, with difficulties still existing in prognosis assessment and patient stratification. Pyroptosis, a newly discovered form of programmed cell death, is involved in cancer pathogenesis and progression. The role of pyroptosis in the tumor microenvironment (TME) of TNBC has not been fully elucidated. In this study, we disclosed global alterations in 58 pyroptosis-related genes at somatic mutation and transcriptional levels in TNBC samples collected from The Cancer Genome Atlas and Gene Expression Omnibus databases. Based on the expression patterns of genes related to pyroptosis, we identified two molecular subtypes that harbored different TME characteristics and survival outcomes. Then, based on differentially expressed genes between two subtypes, we established a 12-gene score with robust efficacy in predicting short- and long-term overall survival of TNBC. Patients at low risk exhibited a significantly better prognosis, more antitumor immune cell infiltration, and higher expression of immune checkpoints including PD-1, PD-L1, CTLA-4, and LAG3. The comprehensive analysis of the immune landscape in TNBC indicated that alterations in pyroptosis-related genes were closely related to the formation of the immune microenvironment and the intensity of the anticancer response. The 12-gene score provided new information on the risk stratification and immunotherapy strategy for highly heterogeneous patients with TNBC.</p

Isogarcinol Extracted from Garcinia mangostana L. Ameliorates Imiquimod-Induced Psoriasis-like Skin Lesions in Mice

Isogarcinol (YDIS), a natural compound extracted from Garcinia mangostana L., has a significant immunosuppressive effect on systemic lupus erythematosus and rheumatoid arthritis. This paper reports that it reduced imiquimod-induced psoriasis-like skin lesions in mice. It strongly attenuated the aberrant proliferation and differentiation of keratinocytes. Moreover, the expression of genes involving the interleukin-23 (IL-23)/T-helper 17 (Th17) axis was significantly inhibited in the dorsal skin of the YDIS-treated mice, as was that of the other pro-inflammatory factors TNF-α, IL-2, and even interferon (IFN)-γ. Furthermore, YDIS prevented the abnormal distribution of T cell types and suppressed the differentiation of CD4⁺ T cells into Th17 cells in the spleens of mice exposed to imiquimod. Interestingly, it elevated numbers of regulatory T cells (Tregs) in the spleen and boosted IL-10 expression in the skin. In agreement with the above, YDIS increased serum IL-10 and reduced serum IL-17. It also caused less damage to the liver and, especially, kidneys of mice than cyclosporine A (CsA). In vitro, YDIS caused more death of HaCaT keratinocytes than CsA. It also strongly inhibited inflammatory factor expression in lipopolysaccharide (LPS)-stimulated HaCaT cells. These findings suggest that YDIS is a promising immunosuppressive agent for treating psoriasis

Toxicity of isogarcinol in mice.

<p>Blood levels of substances in BALB/c mice in control, CsA, and isogarcinol groups. n = 8 for each group. (A) Glutamic-pyruvic transaminase blood level. (B) Glutamic-oxalacetic transaminase blood level. (C) Total bilirubin blood level. (D) Urea nitrogen blood level. (E) Serum creatinine level.</p

Prolongation of allograft skin survival by isogarcinol.

<p>Percentages of graft survival at different times after skin transplantation using Kaplan–Meier survival analysis.</p

Inhibition of CN activity by <i>Garcinia mangostana</i> L. fractions.

<p>(A) SDS-PAGE analysis of purified CN protein. Lane 1: CNA; Lane M: Marker (B) Effects of <i>Garcinia mangostana</i> L. fractions on CN activity. (C) Effects of EtOAc fractions on CN activity. (D) Effects of fractions derived from fraction M on CN activity. (E) Inhibition of CN activity by compound I., Assays were performed with p-NPP as a substrate. CN activity is shown as a percentage of that in the control group. All values are expressed as mean ± SD. n = 3.</p

Inhibition of Con A-stimulated proliferation and MLR by isogarcinol.

<p>(A) Effect of isogarcinol on mouse splenocytes <i>in vitro</i>. Evaluation of different concentrations of isogarcinol and CsA on splenocyte viability, assessed by CCK-8 assay for 72 h. (B) Effect of isogarcinol at different concentrations on Con A-induced lymphocyte proliferation, assessed by CCK-8 assay for 24, 48 and 72 h. (C) Effect of isogarcinol at different concentrations on MLR, assessed by CCK-8 assay for 48, 72 and 96 h. Results are expressed as mean ± SD. n = 5 for each group.</p

Compound I identification.

<p>(A) ¹H-NMR spectrogram of compound I. (B) ¹³C-NMR spectrogram of compound I. (C) ESI-MS of compound I. (D) Chemical structure of isogarcinol.</p