Antimicrobial peptides (AMPs) are small molecular peptides widely existing in the innate immunity of organisms, serving as the first line of defense. Natural AMPs possess various biological activities and are difficult to develop drug resistance. However, they are easily broken down by digestive enzymes in the body. In recent years, increasing methods have been reported to enhance the stability of AMPs, including incorporation of unnatural amino acids, chemical modifications, strategic avoidance of enzyme cleavage sites, cyclization, and nano peptide design. This review summarizes the methods for improving the stability of AMPs against protease degradation, aiming to provide references for further research in this field.
Antimicrobial Peptides/pharmacology* ; Humans ; Peptide Hydrolases/metabolism* ; Protein Stability ; Antimicrobial Cationic Peptides/chemistry* ; Anti-Infective Agents/chemistry*

BACKGROUND: Glutamine synthetase (GS) and arginase 1 (Arg1) are widely used pathological markers that discriminate hepatocellular carcinoma (HCC) from intrahepatic cholangiocarcinoma; however, their clinical significance in HCC remains unclear. METHODS: We retrospectively analyzed 431 HCC patients: 251 received hepatectomy alone, and the other 180 received sorafenib as adjuvant treatment after hepatectomy. Expression of GS and Arg1 in tumor specimens was evaluated using immunostaining. mRNA sequencing and immunostaining to detect progenitor markers (cytokeratin 19 [CK19] and epithelial cell adhesion molecule [EpCAM]) and mutant TP53 were also conducted. RESULTS: Up to 72.4% (312/431) of HCC tumors were GS positive (GS+). Of the patients receiving hepatectomy alone, GS negative (GS-) patients had significantly better overall survival (OS) and recurrence-free survival (RFS) than GS+ patients; negative expression of Arg1, which is exclusively expressed in GS- hepatocytes in the healthy liver, had a negative effect on prognosis. Of the patients with a high risk of recurrence who received additional sorafenib treatment, GS- patients tended to have better RFS than GS+ patients, regardless of the expression status of Arg1. GS+ HCC tumors exhibit many features of the established proliferation molecular stratification subtype, including poor differentiation, high alpha-fetoprotein levels, increased progenitor tumor cells, TP53 mutation, and upregulation of multiple tumor-related signaling pathways. CONCLUSIONS GS- HCC patients have a better prognosis and are more likely to benefit from sorafenib treatment after hepatectomy. Immunostaining of GS may provide a simple and applicable approach for HCC molecular stratification to predict prognosis and guide targeted therapy.
Humans ; Carcinoma, Hepatocellular/metabolism* ; Sorafenib/therapeutic use* ; Liver Neoplasms/metabolism* ; Glutamate-Ammonia Ligase/metabolism* ; Hepatectomy ; Retrospective Studies ; Prognosis ; Neoplasm Recurrence, Local/surgery*

Successful pregnancy in placental mammals substantially depends on the establishment of maternal immune tolerance to the semi-allogenic fetus.Disorders in this process are tightly asso-ciated with adverse pregnancy outcomes including recurrent miscarriage (RM).However,an in-depth understanding of the systematic and decidual immune environment in RM remains largely lacking.In this study,we utilized single-cell RNA-sequencing (scRNA-seq) to comparably analyze the cellular and molecular signatures of decidual and peripheral leukocytes in normal and unex-plained RM pregnancies at the early stage of gestation.Integrative analysis identifies 22 distinct cell clusters in total,and a dramatic difference in leukocyte subsets and molecular properties in RM cases is revealed.Specifically,the cytotoxic properties of CD8+ effector T cells,nature killer(NK),and mucosal-associated invariant T (MAIT) cells in peripheral blood indicates apparently enhanced pro-inflammatory status,and the population proportions and ligand-receptor interac-tions of the decidual leukocyte subsets demonstrate preferential immune activation in RM patients.The molecular features,spatial distribution,and the developmental trajectories of five decidual NK(dNK) subsets have been elaborately illustrated.In RM patients,a dNK subset that supports embryonic growth is diminished in proportion,while the ratio of another dNK subset with cyto-toxic and immune-active signature is significantly increased.Notably,a unique pro-inflammatory CD56 + CD16 + dNK subset substantially accumulates in RM decidua.These findings reveal a com-prehensive cellular and molecular atlas of decidual and peripheral leukocytes in human early pregnancy and provide an in-depth insight into the immune pathogenesis for early pregnancy loss.

Nanotechnology has emerged as an ideal approach for achieving the efficient chemo agent delivery. However, the potential toxicity and unclear internal metabolism of most nano-carriers was still a major obstacle for the clinical application. Herein, a novel "core‒shell" co-assembly carrier-free nanosystem was constructed based on natural sources of ursolic acid (UA) and polyphenol (EGCG) with the EpCAM-aptamer modification for hepatocellular carcinoma (HCC) synergistic treatment. As the nature products derived from food-plant, UA and EGCG had good anticancer activities and low toxicity. With the simple and "green" method, the nanodrugs had the advantages of good stability, pH-responsive and strong penetration of tumor tissues, which was expected to increase tumor cellular uptake, long circulation and effectively avoid the potential defects of traditional carriers. The nanocomplex exhibited the low cytotoxicity in the normal cells

Purpose: Anterior gradient 3 (AGR3) belongs to human anterior gradient (AGR) family. The function of AGR3 on cancer remains unknown. This research aimed to investigate if AGR3 had prognostic values in invasive ductal carcinoma (IDC) of breast cancer and could promote tumor progression. Materials and Methods: AGR3 expression was detected in breast benign lesions, ductal carcinoma in situ and IDC by immunohistochemistry analysis. AGR3’s correlations with clinicopathological features and prognosis of IDC patients were analyzed. By cell function experiments, collagen gel droplet-embedded culture drug sensitivity test and cytotoxic analysis, AGR3’s impacts on proliferation, invasion ability, and chemotherapeutic drug sensitivity of breast cancer cells were also detected. Results: AGR3 was up-regulated in luminal subtype of histological grade I-II of IDC patients and positively correlated with high risks of recurrence and distant metastasis. AGR3 high expression could lead to bone or liver metastasis and predict poor prognosis of luminal B. In cell lines, AGR3 could promote proliferation and invasion ability of breast cancer cells which were consistent with clinical analysis. Besides, AGR3 could indicate poor prognosis of breast cancer patients treated with taxane but a favorable prognosis with 5-fluoropyrimidines. And breast cancer cells with AGR3 high expression were resistant to taxane but sensitive to 5-fluoropyrimidines. Conclusion AGR3 might be a potential prognostic indicator in luminal B subtype of IDC patients of histological grade I-II. And patients with AGR3 high expression should be treated with chemotherapy regimens consisting of 5-fluoropyrimidines but no taxane.

Objective? To explore the correlation between spinal cord function and the risk of pressure injury in patients with spinal dural arteriovenous fistula (SDAVF). Methods? A total of 65 patients with SDAVF treated in Neurosurgery Department in Xuanwu Hospital between March 2013 and December 2016 was carried out. The Modified Aminoff-Logue Score (mALS) and Braden pressure Ulcer Risk Factor Assessment Scale were used to evaluated the spinal cord and the risk of pressure ulcers of the patients with SADVF. Spearman was used to analyze the correlation. Results? The Preoperative mALS was (5.15±2.62), and the Braden score was (20.88±2.09). The postoperative Braden score was (17.25±1.61), The result of Spearman correlation analysis showed that the total score of preoperative mALS was negatively correlated with the total score of Braden (r=-0.597, P＜ 0.01). Conclusions? Preoperative spinal cord function was slightly impaired in patients with SDAVF. The risk of postoperative pressure injury decreased when patients have better spinal cord function. The risk of pressure injury after operation is higher than that before operation.

Objective To detect the protective mechanism of trehalose in tracheal cryopreservation.Methods Inbred male Sprague-Dawley (SD) rats were sacrificed with intraperitoneal injection of ketamine(150mg?kg -1).The tracheas were removed and immersed immediately in the freezing medium of low potassium dextran (LPD) solution only(Group Ⅰ) ,containing with 10% dimethylsulfoxide(DMSO)(Group Ⅱ), containing with 0.15mol?L -1 trehalose (Group Ⅲ),and containing with 10% DMSO and 0.15mol?L -1 trehalose (Group Ⅳ) respectively. A sterile plastic tube containing a 1-cm-long trachea was filled with the freezing medium,sealed,and frozen to -80℃ at rate of -1℃ per minute in a programmable freezer.Then the tube was stored in liquid nitrogen(-196℃) for 20 days. Then the specimen was thawed in a 37℃ water bath and rinsed with physiologic saline solution 10 times.Histologic changes before cryopreservation and after thawing were examined in each group. After the specimens were embedded in paraffin,5-(m-thick sections were stained with hematoxylin and eosin.The epithelium and cartilage was assessed. We also observed Bcl-2 and Bax gene expression by immunohistochemistry. At last, some tracheas(SD) after cryopreservation were thawed and transplanted into the abdominal cavity of Wistar rats. The transplanted tracheas were retrieved and assessed histologically.Results Microscopic findings of the tracheas in Group Ⅲ and Group Ⅳ showed their structure were intact and Bax gene expression was lower in cartilage after cryopreservation(20d) compared with other groups,especially in Group Ⅳ.The tracheas in Group Ⅲ and Group Ⅳ grew well after they were transplanted into cavity of Wistar rats heterotopically,too.There were no significant differences among 4 groups in Bcl-2 gene expression.Conclusion In tracheal cryopreservation the trehalose can protect the trachea by protecting the tracheal cartilage.It is one of the protective mechanism that the trehalose inhibit the Bax gene expression of cartilage cells.The concomitant use of trehalose and DMSO has a synergistic effect.