Fig 2: Effects of BHS on LPS-induced amyloidogenesis, neuroinflammation, NF-?B/MAPK activation, and mRNA expression of inflammatory mediators in the mouse brain. Protein expression levels of (A) APP, C99, and BACE-1 and (B) Iba-1, GFAP, iNOS, and COX-2 were detected by Western blotting. (C) Activation of NF-?B and MAPK pathways. (D) mRNA expression of inflammatory mediators was analyzed by RT-qPCR. Histograms show protein or mRNA levels relative to those of an internal control such as ß-actin or total-type protein. Data represent means ± SEM. # p < 0.05 compared with the Normal group; * p < 0.05, ** p < 0.001, and † p < 0.0001 compared with the LPS group. APP, amyloid-ß precursor protein; BACE-1, ß-secretase-1; BHS, banhasasim-tang; C99, ß-CTF fragment of APP; COX-2, cyclooxygenase-2; ERK, extracellular signal-regulated kinase; GFAP, glial fibrillary acidic protein; HO-1, heme oxygenase; Iba-1, ionized calcium-binding adaptor molecule 1; Indo, indomethacin; iNOS, inducible nitric oxide synthase; IL-1ß, interleukin 1ß; IL-6, interleukin 6; JNK, c-Jun NH2-terminal kinase; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; NF-?B, nuclear factor ?B; TNF-a, tumor necrosis factor alpha.

Fig 3: Activation of mitogen activated protein kinase (MAPK) in ZIKV infected trophoblasts.a Immunoblot analysis of JNK and p38 activation via phosphorylation were observed 8–24 h after infection with 0.1 MOI r-MRV in JEG-3 cells showed increase in phosphorylation of p54 and p46 components of JNK and phosphorylation of p38 MAPK as well compared to uninfected vehicle cells. Similarly, JNK and p38 activation via phosphorylation was also observed in JAR cells (b) and HTR-8 (c) 24 h of postinfection with 0.1 MOI r-MRV compared to uninfected vehicle cells. Total JNK and Total p38 levels were mostly unaltered between ZIKV infected and vehicle uninfected cells. d Activation of JNK was also seen with 0.1 MOI PRV 24–48 h of postinfection in JEG-3 cells compared to uninfected vehicle cells.

Fig 4: OJS treatment inhibits the activation of MAPK and NF-?B pathways in cisplatin-induced AKI. (A) The phosphorylation levels of p38, ERK1/2, and JNK were analyzed by western blotting. Total p38, ERK1/2, and JNK were used as loading controls. (B) The relative density ratio of phosphorylated form/total form. (C) The degradation of I?-Ba was analyzed by western blotting. ß-actin was used as a loading control. (D) The relative density ratio of I?-Ba/ß-actin. Data are represented as mean ± S.E.M. (n = 6; * indicates p < 0.05 vs. saline-treated control group, † indicates p < 0.05 vs. cisplatin treatment alone).

Fig 5: S100A8 and S100A9 suppress tumorigenesis induced by xenograft of EoL-1 and EoL-1-1R in NOD-SCID mice. (A–F) Five-week-old female NOD-SCID (NOD.CB17-Prkdcscid/J) mice were divided into six groups (n = 5 per a group) as described in the materials and methods: untreated, control, S100A8 treatment (0.5 and 1 mg doses), and S100A9 treatment (0.5 and 1 mg doses). The control, S100A8 treatment, and S1009 treatment groups were subcutaneously inoculated in the shoulder with EoL-1 cells (2 × 107/100 µL) (A–C) or EoL-1-IR cells (1 × 107/100 µL) (D–F). Treatment groups were subsequently administered subcutaneous doses of 0.5 or 1 mg S100A8 or S100A9 at days 5 and 7 after cell inoculation. The untreated group was injected with vehicle (PBS). Tumor volume (day 1–11) and tumor weight (day 11) were measured (A,B,D,E). Tumor mass was examined for detecting phospho-PDGFRa, PDGFRa, and Ki-67, applying immunohistochemistry and hematoxylin and eosin stain (Scale bar: 200 µm) (C,F), or subjected to Western blotting to determine phosphorylation and nonphosphorylation of PDGFRa, STAT3, AKT, ERK1/2, p38 MAPK, and JNK (G). ß-actin was used as the internal control. *p < 0.05 indicates a significant difference between the control and stimulator-treated groups.