Antimicrobial peptide HI-3 from Hermetia illucens alleviates inflammation in lipopolysaccharide-stimulated RAW264.7 cells via suppression of the nuclear factor kappa-B signaling pathway.

Hermetia illucens-3 (HI-3), an active insect antimicrobial peptide extracted from H. illucens larvae, exerts antibacterial and anticancer activity. However, the inflammatory effects and their relative molecular mechanisms remain unclear. To explore the inflammatory effects of HI-3, an inflammatory model was induced using 1 ng/mL LPS in RAW264.7 cells. The cell viability and phagocytosis of LPS-stimulated RAW264.7 cells were then detected after HI-3 treatment. Furthermore, the antioxidant activity, the levels of proinflammatory cytokines, and the expression levels of both p65 and inhibitor of nuclear factor kappa B (IκB) were measured. Results showed that HI-3 could inhibit the differentiation, proliferation, phagocytosis, and antioxidant ability, as well as the secretion and messenger RNA expression levels of IL-6, TNF-α, and IL-1ß of LPS-induced RAW264.7 cells in a dose-dependent manner. At the same time, the level of the anti-inflammatory cytokine IL-10 was increased after HI-3 treatment. Western blotting results showed that HI-3 suppressed LPS-induced p65 and IκB activation in a dose-dependent manner. Therefore, HI-3 exerts its anti-inflammatory effect by inhibiting the expression of proinflammatory cytokines and the activation of p65 and IκB, which indicated that HI-3 could be a promising therapeutic medicine for inflammation.

The Risk of Postpartum Hemorrhage Following Prior Prelabor Cesarean Delivery Stratified by Abnormal Placentation: A Multicenter Historical Cohort Study.

Background: Prior prelabor cesarean delivery (CD) was associated with an increase in the risk of placenta previa (PP) in a second delivery, whether it may impact postpartum hemorrhage (PPH) independent of abnormal placentation. This study aimed to assess the risk of PPH stratified by abnormal placentation following a first CD before the onset of labor (prelabor) or intrapartum CD. Methods: This multicenter, historical cohort study involved singleton, pregnant women at 28 weeks of gestation or greater with a CD history between January 2017 and December 2017 in 11 public tertiary hospitals within 7 provinces of China. PPH was analyzed in the subsequent pregnancy between women with prior prelabor CD and women with intrapartum CD. Furthermore, PPH was analyzed in pregnant women stratified by complications with PP alone [without placenta accreta spectrum (PAS) disorders], complications with PP and PAS, complications with PAS alone (without PP), and normal placentation. We performed multivariate logistic regression to calculate adjusted odds ratios (aOR) and 95% CI controlling for predefined covariates. Results: Out of 10,833 pregnant women, 1,197 (11%) women had a history of intrapartum CD and 9,636 (89%) women had a history of prelabor CD. Prior prelabor CD increased the risk of PP (aOR 1.91, 95% CI 1.40-2.60), PAS (aOR 1.68, 95% CI 1.11-2.24), and PPH (aOR 1.33, 95% CI 1.02-1.75) in a subsequent pregnancy. After stratification by complications with PP alone, PP and PAS, PAS alone, and normal placentation, prior prelabor CD only increased the risk of PPH (aOR 3.34, 95% CI 1.35-8.23) in a subsequent pregnancy complicated with PP and PAS. Conclusion: Compared to intrapartum CD, prior prelabor CD increased the risk of PPH in a subsequent pregnancy only when complicated by PP and PAS.

Evaluation of PAP in EGFR Mutational Testing in Advanced NSCLC: a Comparative Study.

BACKGROUND: EGFR mutational testing is crucial for advanced non-squamous NSCLC. PAP is a sensitive and selective method to detect rare mutations. METHODS: Eighty-five patients with non-squamous NSCLC were enrolled in this study. A set of paired plasma samples from each patient were collected and detected by PAP and ARMS. RESULTS: Of 85 paired samples, 78.8% (67/85) presented the same mutational status by the two methods. There was no statistically significant difference between the mutation frequencies in plasma samples detected with PAP and ARMS (p = 0.096). CONCLUSIONS: PAP technology appears to be an alternative choice with relatively high sensitivity for the detection of plasma EGFR mutations.

EGFR exon 20 insertion mutation in advanced thymic squamous cell carcinoma: Response to apatinib and clinical outcomes.

Thymic carcinoma (TC) is a rare malignant tumor of the mediastinum with occult onset, rapid development, and poor prognosis. Surgery is the main treatment for early TC, but the majority of patients are diagnosed at Masaoka-Koga stage III or IV with local invasion or distant metastasis. Platinum and anthracyclines are currently considered key components of first-line chemotherapy for advanced TC; however, there are no standard treatment plans for patients who are refractory to first-line and further chemotherapy. The clinical effect is also unsatisfactory. Apatinib has been successfully applied as third-line treatment for advanced gastric cancer and has shown high efficacy in the treatment of various cancers, such as lung, liver, and colorectal cancers. Herein we report a case of advanced thymic squamous cell carcinoma harboring EGFR exon 20 insertion in which apatinib was administered after multi-line chemotherapy and radiotherapy and a partial response was achieved after five months of treatment. To date, a five month overall response and 10 months of progression-free survival have been achieved. Adverse reactions can be controlled and the patient's quality of life has improved. Apatinib provides a new option for clinicians to treat patients with advanced TC.

Roles of ROS/TACE in neutrophil elastase-induced mucus hypersecretion in NCI-H292 airway epithelial cells.

Complications arise in chronic obstructive pulmonary diseases (COPD) with excessive mucus production, especially during the exacerbation period, which contributes to airway blockage and bacterial infection. Neutrophil elastase (NE) is detected at high levels in airway secretions, and is the primary inducer of mucin production. Understanding the mechanism of NE-induced overproduction of mucin may lead to new therapies for COPD. It is known that activation of epidermal growth factor receptor (EGFR) and its downstream signaling cascade are involved in mucin production. However, the mechanism of NE-induced EGFR activation remains unclear. Tumor necrosis factor-α-converting enzyme (TACE) cleaves pro-transforming growth factor (TGF)-α in airway epithelial cells to release the mature, soluble TGF-α form, which subsequently binds to and activates EGFR. In this investigation, we demonstrate that NE-induced mucin production requires reactive oxygen species (ROS) production, which activates TACE, resulting in TGF-α shedding, and EGFR phosphorylation in NCI-H292 epithelial cells.

Regulation of neutrophil elastase-induced MUC5AC expression by nuclear factor erythroid-2 related factor 2 in human airway epithelial cells.

Mucin 5AC (MUC5AC) is one of the main airway mucins implicated in pulmonary diseases with mucous hypersecretion. Neutrophil elastase (NE), a serine protease released by neutrophils, is known to induce MUC5AC synthesis by increasing reactive oxygen species (ROS) generation. Nuclear factor erythroid-2 related factor 2 (Nrf2), a basic-region leucine-zipper transcription factor, is believed to protect against ROS damage by activating a series of antioxidant enzymes; Nrf2 is also reported to reduce NE activity. The aim of our study was to examine the relationship between Nrf2 expression and NE-induced MUC5AC production. We used a small interfering RNA to inhibit Nrf2 expression. The Nrf2 gene and protein expressions were assessed by quantitative real-time polymerase chain reaction, and Western blotting, respectively. The ROS generation was examined using a kit. The expression of MUC5AC was assessed using enzyme-linked immunosorbent assay. The results showed that NCI-H292 epithelial cells, in which the Nrf2 gene expression repressed, were highly predisposed to NE stimulation, with marked exacerbation of ROS generation and reduced secretory leukocyte protease inhibitor production, resulting in high MUC5AC expression. Pretreatment with the potent Nrf2 activator sulforaphane had the reverse effect. These results demonstrate that Nrf2 is a novel nuclear factor involved in down-regulating MUC5AC synthesis by inhibiting ROS generation and augmenting proteinase inhibitor production.

Bilateral traumatic carotid cavernous fistula: the manifestations, transvascular embolization and prevention of the vascular complications after therapeutic embolization.

Bilateral traumatic carotid cavernous fistula is very rare after traumatic brain and facial injury. We present a 68-year-old woman with bilateral traumatic carotid cavernous fistula, who was treated with transarterial embolization by detachable balloon on both fistulas and recovered completely. We also reviewed the presentations, treatment and the complications after the transarterial embolization of this disorder.