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To assess the clinical value of serum complement component 1q (C1q) and immunoglobulin G (IgG) levels in predicting the response to combined immunotherapy in patients with esophageal squamous cell carcinoma. We conducted a retrospective study of 44 patients with esophageal squamous cell carcinoma who received combined immunotherapy in our hospital. Serum IgG and C1q levels were collected before and three weeks after immunotherapy treatment, together with other data on clinical and demographic characteristics. Twenty seven patients (61.4%) showed partial response (PR), 13 (29.5%) stable disease (SD), and 4 (9.1%) progressive disease (PD). None of the patients presented complete response (CR). The PR group displayed lower IgG and higher C1q levels both before and after immunotherapy than patients showing SD or PD. The IgG reduction (59.3%) and C1q increment (70.3%) in the PR group three weeks post-treatment were significantly larger than those in patients showing SD or PD. Moreover, the pretreatment C1q level and the post-treatment change of C1q levels were strongly associated with the immunotherapy response. High pre- and post-treatment C1q levels and reduced post-treatment IgG levels correlate with efficacy of combined immunotherapy in patients with esophageal squamous cell carcinoma. Serum baseline C1q level may predict immunotherapy response in such patients. [ABSTRACT FROM AUTHOR]

Astragaloside IV (AS-IV), a main active substance isolated fromAstragalus membranaceus Bunge, has been shown to have multiple pharmacological effects. Endothelial cell protein C receptor (EPCR) is a marker of inflammation, and is also a major member of protein C (PC) anti-coagulation system. EPCR can be cut off from the cell surface by tumor necrosis factor-α converting enzyme (TACE), which is controlled through mitogen-activated protein kinase (MAPK) and protein kinase C (PKC) pathways. To develop novel therapeutic drug for EPCR shedding, the effect of AS-IV was studied in phorbol-12-myristate 13-acetate (PMA)-induced human umbilical vein endothelial cells (HUVECs) and the potential molecular mechanism of AS-IV action was investigated. The results showed that AS-IV could significantly inhibit PMA-induced EPCR shedding. In further study, AS-IV suppressed the expression and activity of TACE. In addition, AS-IV could decrease the phosphorylation of MAPK such as janus kinase (JNK) and p38, and inhibit activation of PKC through the prevention of non-phosphorylation and phosphorylation of specific PKC isoforms in PMA-stimulated HUVECs. These findings indicate that AS-IV may be used as a natural medicine to treat EPCR-related systemic inflammation and cardiovascular diseases by targeting MAPK and PKC pathway. [ABSTRACT FROM PUBLISHER]

The interleukin-23/interleukin 17A (IL-23/IL-17A) cytokine axis plays a critical role in the pathogenesis of psoriasis. In this study, we report the effects of topical calcipotriol, camptothecin, clobetasol and tazarotene on the treatment of imiquimod (IMQ)-induced psoriasis-like inflammation, the development of which is dependent on the IL-23/IL-17A axis. IMQ-induced epidermal hyperplasia and inflammation in the BALB/c mouse ear were significantly inhibited following clobetasol treatment but not calcipotriol, camptothecin or tazarotene treatments. Real-time polymerase chain reaction showed that the mRNA levels of IL-17A, IL-17F, IL-22, IL-1β, IL-6 and TNF-α in ear skin were significantly decreased by clobetasol. In addition, we observed that calcipotriol, camptothecin and tazarotene failed to show any inhibitory effects on the IL-23/IL-17A/IL-22 axis. We also found that clobetasol treatment inhibited the proliferation of γδ T cells and C-C chemokine receptor type 6 (CCR6) expression induced by IMQ. Calcipotriol, camptothecin and tazarotene not only failed to inhibit this proliferation but also enhanced retinoic acid-related orphan receptor γ (RORγ) expression in IMQ-induced psoriasis-like inflammation. In conclusion, we suggest that clobetasol induces the relief of IMQ-induced psoriasis-like inflammation in a mouse model but that calcipotriol, camptothecin and tazarotene cannot. Therefore, we suggest that more in-depth studies on pharmacological effects of tazarotene, camptothecin and calcipotriol should be carried out. [ABSTRACT FROM AUTHOR]