Wenjuan Li

Background: Vasculogenic mimicry (VM) is a recently identified pattern of blood supply to tumor tissue. It has long been considered a functional element in the metastasis and prognosis of malignant tumors. Both Rho GTPase-activating protein 25 (ARHGAP25) and Ras homolog family member A (RhoA) are effective predictors of tumor metastasis. In this study, we examined the expression levels of ARHGAP25 and RhoA and the structure of VM in non-small cell lung cancer (NSCLC). At the same time, we used cytology-related experiments to explore the effect of ARHGAP25 on the migration ability of tumor cells. Furthermore, we analyzed the interaction between the three factors and their association with clinicopathological characteristics and the five-year survival time in patients using statistical tools. Methods: A total of 130 well-preserved NSCLC and associated paracancerous tumor-free tissues were obtained. Cell colony formation, wound healing, and cytoskeleton staining assays were used to analyze the effect of ARHGAP25 on the proliferation and migration ability of NSCLC cells. Immunohistochemical staining was used to determine the positivity rates of ARHGAP25, RhoA, and VM. Statistical software was used to examine the relationships between the three factors and clinical case characteristics, overall survival, and disease-free survival. Results: Cell colony formation, wound healing, and cytoskeleton staining assays confirmed that ARHGAP25 expression affects the proliferation and migratory abilities of NSCLC cells. ARHGAP25 positivity rates in NSCLC and paracancerous tumor-free tissues were 48.5% and 63.1%, respectively, whereas RhoA positivity rates were 62.3% and 18.5%, respectively. ARHGAP25 had a negative relationship with RhoA and VM, whereas RhoA and VM had a positive relationship (P < 0.05). ARHGAP25, RhoA, and VM affected the prognosis of patients with NSCLC (P < 0.05) according to Kaplan–Meier of survival time and Cox regression analyses. Furthermore, lowering ARHGAP25 expression increased NSCLC cell proliferation and migration. Conclusions: ARHGAP25 and RhoA expression is associated with VM and may be of potential value in predicting tumor metastasis, prognosis, and targeted therapy.

Porcine transmissible gastroenteritis virus (TGEV) is a pathogenic agent responsible for high diarrhea-associated morbidity and mortality in suckling piglets. To understand the genomic characteristics and evolutionary trend of TGEV during nearly 70 years, we reanalyzed published TGEV whole genome sequences. The genomic sequences of 40 strains from different sources were downloaded from National Center for Biotechnology Information. The phylogenetic analysis was performed using both whole genome sequences and S gene sequences. The regional distribution of TGEV virus was obvious while the time distribution was relatively scattered. In the whole genome sequences, 2505 variable sites were found and 56% of them occurred more than once. In S gene sequences, 505 variable sites were detected, which generated 191 amino acid mutations.

Background: To explore adverse drug reactions (ADRs) and the effects of nursing interventions after Aidi injection for the treatment of non-Hodgkin’s lymphoma (NHL). Methods: A total of 104 NHL patients treated in our hospital from March 2019 to March 2020 were selected. All patients underwent conventional chemotherapy, with a concomitant Aidi injection administered at different doses (40, 60, 80, and 100 mL). ADRs were analyzed for all patients, and the clinical outcomes of ADRs were recorded after specific nursing interventions were performed. Results: A total of 17 NHL patients had ADRs, with a total incidence rate of 15.89% (total of 30 ADRs). In terms of different types of ADRs, inappetence accounted for the largest proportion, followed by skin pruritus and fever, phlebitis, nausea and vomiting, and chest distress and/or palpitation, the last of which shared the same proportion as chills and/or low fever and urticaria. The incidence rate of ADRs (total of 18 ADRs, 60.00%) was higher in NHL patients who were given 100 mL of Aidi injection. In terms of age and gender distribution of ADRs, there were 10 males (55.56%) and 7 females (44.44%), and ADRs were more common in patients aged 46-60 years old (total of 6 ADRs, 35.29%). Aidi injection mainly induced mild ADRs (total of 22 ADRs, 73.33%), and the resulting ADRs mostly occurred for Conclusions: Particular attention should be paid to ADRs in the treatment of NHL patients with Aidi injection. After ADRs occur, specific nursing interventions can aid in recovery and lead to improvements in prognosis.

CXC chemokine receptor 4 (CXCR4) is a co-receptor for HIV-1 entry into target cells. Its natural ligand, the chemokine SDF-1, inhibits viral entry mediated by this receptor. However, the broad expression pattern of CXCR4 and its critical roles in various physiological and pathological processes indicate that the direct application of SDF-1 as an entry inhibitor might have severe consequences. Previously, we constructed an effective SDF-1 mutant, SDF-1/54, by deleting the α-helix of the C-terminal functional region of SDF-1. Of note, SDF-1/54 shows remarkable decreased chemotoxic ability, but maintains a similar binding affinity to CXCR4, suggesting SDF-1/54 might better serve as a CXCR4 inhibitor. Here, we found that SDF-1/54 exhibited potent antiviral activity against various X4 HIV-1 strains, including the infectious clone HIV-1 NL4-3, laboratory-adapted strain HIV-1 IIIB, clinical isolates and even drug-resistant strains. By using time-of-addition assay, non-infectious and infectious cell–cell fusion assay and CXCR4 internalization assay, we demonstrated SDF-1/54 is an HIV-1 entry inhibitor. A combination of SDF-1/54 with several antiretroviral drugs exhibited potent synergistic anti-HIV-1 activity. Moreover, SDF-1/54 was stable and its anti-HIV-1 activity was not significantly affected by the presence of seminal fluid, vaginal fluid simulant and human serum albumin. SDF-1/54 showed limited in vitro cytotoxicity to lymphocytes and vaginal epithelial cells. Based on these findings, SDF-1/54 could have a therapeutic potential as an HIV-1 entry inhibitor.

Eukaryotic translation initiation factor 3 (eIF3) plays an important role in the regulation of mRNA translation, cell growth and cancer development. eIF3b is the main scaffolding subunit in the eIF3 complex and has been demonstrated to contribute to the development of several cancers. First, our study found that the downregulation of eIF3b could inhibit the proliferation and metastasis of gastric cancer cells by regulating the expression of cancer-related genes. In addition, the expression of eIF3b correlated with the stage and progression of gastric cancer and was shown to be upregulated in human chronic gastritis and in gastric cancer tissues compared with the expression of eIF3b in normal gastric tissues. Moreover, Helicobacter pylori (H. pylori) infection could upregulate the expression of eIF3b in gastric cancer cells, suggesting that eIF3b might be involved in the carcinogenic process of H. pylori. The above findings identified the oncogenic role of eIF3b in gastric cancer development, and this may contribute to the exploration and discovery of novel therapeutic targets for gastric cancer treatment.

Semen-derived amyloid fibrils, comprising SEVI (semen-derived enhancer of viral infection) fibrils and SEM1 fibrils, could remarkably enhance HIV-1 sexual transmission and thus are potential targets for the development of an effective microbicide. Previously, we found that ADS-J1, apart from being an HIV-1 entry inhibitor, could also potently inhibit seminal amyloid fibrillization and block fibril-mediated enhancement of viral infection. However, the remodeling effects of ADS-J1 on mature seminal fibrils were unexplored. Herein, we investigated the capacity of ADS-J1 to disassemble seminal fibrils and the potential mode of action by applying several biophysical and biochemical measurements, combined with molecular dynamic (MD) simulations. We found that ADS-J1 effectively remodeled SEVI, SEM1_86–107 fibrils and endogenous seminal fibrils. Unlike epigallocatechin gallate (EGCG), a universal amyloid fibril breaker, ADS-J1 disaggregated SEVI fibrils into monomeric peptides, which was independent of oxidation reaction. MD simulations revealed that ADS-J1 displayed strong binding potency to the full-length PAP_248–286 via electrostatic interactions, hydrophobic interactions and hydrogen bonds. ADS-J1 might initially bind to the fibrillar surface and then occupy the amyloid core, which eventually lead to fibril disassembly. Furthermore, the binding of ADS-J1 with PAP_248–286 might induce conformational changes of PAP_248–286. Disassembled PAP_248–286 might not be favorable to re-aggregate into fibrils. ADS-J1 also exerts abilities to remodel a panel of amyloid fibrils, including Aβ_1–42, hIAPP_1–37 and EP2 fibrils. ADS-J1 displays promising potential to be a combination microbicide and an effective lead-product to treat amyloidogenic diseases.

Semen-derived amyloid fibrils, composing SEVI (semen-derived enhancer of viral infection) fibrils and SEM1 fibrils, could remarkably enhance HIV-1 sexual transmission and thus, are potential targets for the development of an effective microbicide. Previously, we found that ADS-J1, apart from being an HIV-1 entry inhibitor, could also potently inhibit seminal amyloid fibrillization and block fibril-mediated enhancement of viral infection. However, the remodeling effects of ADS-J1 on mature seminal fibrils were unexplored. Herein, we investigated the capacity of ADS-J1 to disassemble seminal fibrils and the potential mode of action by applying several biophysical and biochemical measurements, combined with molecular dynamic (MD) simulations. We found that ADS-J1 effectively remodeled SEVI, SEM1 _86-107 fibrils and endogenous seminal fibrils. Unlike epi-gallocatechin gallate (EGCG), a universal amyloid fibril breaker, ADS-J1 disaggregated SEVI fibrils into monomeric peptides, which was independent of oxidation reaction. MD simulations revealed that ADS-J1 displayed strong binding potency to the full-length PAP _248-286 via electrostatic interactions, hydrophobic interactions and hydrogen bonds. ADS-J1 might initially bind to the fibrillar surface and then occupy the amyloid core, which eventually lead to fibril disassembly. Furthermore, the binding of ADS-J1 with PAP _248-286 might induce conformational changes of PAP _248-286 . Disassembled PAP _248-286 might not be favor to re-aggregate into fibrils. ADS-J1 also exerts abilities to remodel a panel of amyloid fibrils, including Aβ _1-42 , hIAPP _1-37 and EP2 fibrils. ADS-J1 displays promising potential to be a combination microbicide and an effective lead-product to treat amyloidogenic diseases.

Background: This study was in order to understand difference of the clinical characteristics and outcome between interstitial lung disease with dermatomyositis and idiopathic interstitial pneumonia. Methods: We performed a retrospective case-contral study in patients with ILD with DM or IPF from January 2003 to March 2014 in the third affiliated hospital of Sun Yat-sen University. Variables of interest included respiratory symptoms, HRCT features, distribution at CT, ICU stay, steroids therapy, immunosuppressive therapy, and the 90-day mortality. The study was approved by the Institutional Review Board of the hospital. Results: Of the 64 patients (44 ILD with DM and 20 were IPF), the main HRCT features were interlobular septal thickening (68.8%), intralobular reticular opacities(62.5%), non-septal linear or plate-like opacities(68.8%), honeycombing(32.8%). ILD with DM occurs more commonly in females (P 0.004). Between two groups gender, cough(P 0.02) was more frequent in ILD with DM group. Intralobular reticular opacities (P 0.013) and honeycombing(P 0.000) were more frequent in IPF group. Diffuse distribution at CT was more frequent in IPF group. Steroids therapy(P 0.000) was used more for ILD with DM. There was no difference in the 90-day mortality between groups. Conclusions: ILD with DM occurs more commonly in females. Cough was more frequent in ILD with DM group. Intralobular reticular opacities, honeycombing and diffuse distribution at CT were more frequent in IPF group. Although steroids therapy was used more for ILD with DM group, there was no difference in the 90-day mortality between groups.