The Versatile Manipulations of Self-Assembled Proteins in Vaccine Design.

Protein assemblies provide unique structural features which make them useful as carrier molecules in biomedical and chemical science. Protein assemblies can accommodate a variety of organic, inorganic and biological molecules such as small proteins and peptides and have been used in development of subunit vaccines via display parts of viral pathogens or antigens. Such subunit vaccines are much safer than traditional vaccines based on inactivated pathogens which are more likely to produce side-effects. Therefore, to tackle a pandemic and rapidly produce safer and more effective subunit vaccines based on protein assemblies, it is necessary to understand the basic structural features which drive protein self-assembly and functionalization of portions of pathogens. This review highlights recent developments and future perspectives in production of non-viral protein assemblies with essential structural features of subunit vaccines.

[Mechanism of Danggui Sini Decoction in treatment of primary dysmenorrhea based on network pharmacology and molecular docking].

Network pharmacology, molecular docking and in vivo experiments were used to explore the pharmacodynamic basis and potential mechanism of Danggui Sini Decoction in the treatment of primary dysmenorrhea(PD). The chemical constituents of Danggui(Angelicae Sinensis Radix), Guizhi(Cinnamomi Ramulus), Tongcao(Tetrapanacis Medulla), Baishao(Paeoniae Radix Alba), Xixin(Asari Radix et Rhizoma), Gancao(Glycyrrhizae Radix et Rhizoma), and Dazao(Jujubae Fructus) from Danggui Sini Decoction were retrieved through TCMSP(Traditional Chinese Medicine Systems Pharmacology Database), and the action targets of Danggui Sini Decoction were collected through DrugBank. "Primary dysmenorrhea" and "dysmenorrhea" were used as the key words to search the corresponding targets in the GeneCards, OMIM and TTD databases, and then the intersection targets of Danggui Sini Decoction and the primary dysmenorrhea targets were taken for reverse screening to obtain the corresponding active ingredients. Cytoscape 3.6.1 software was used to construct a traditional Chinese medicine-compound-target-disease network; STRING database was used to build a protein-protein interaction(PPI) network; Gene ontology(GO) function enrichment analysis and Kyoto encyclopedia of genes and genomes(KEGG) pathway enrichment analysis were conducted by using DAVID database. The action mechanism of the intersection targets were then predicted, and a histogram chart and bubble chart were drawn for visualization. Then the top five targets in the PPI network were used for docking with the most compounds. In animal experiments, Sprague Dawley(SD) female rats were used to establish a primary dysmenorrhea model by intraperitoneal injection of diethylstilbestrol once a day. A total of 60 SD female rats were randomly divided into 6 groups, namely control group, model group, Danggui Sini Decoction low(1.5 g·kg~(-1)), medium(3.0 g·kg~(-1)), high(6.0 g·kg~(-1)) dose groups, and ibuprofen(20 mg·kg~(-1)) positive control group, with 10 rats in each group. From day 4, except for the control group, rats in the other groups were given intragastric administration of corresponding drugs, and the control group received intragastric administration of normal saline for 7 consecutive days. The number of writhing before and after the administration, the ute-rine contraction inhibition rate and the uterine index after administration were observed, and ELISA assay was used to detect the levels of prostaglandin-endoperoxide synthase 2(PTGS2) and vascular endothelial growth factor A(VEGFA) in the tissues of each group as well as the levels of serum inflammatory factors interleukin 1(IL-1), interleukin 6(IL-6), and tumor necrosis factor-alpha(TNF-α). According to network analysis, 7 Chinese medicines contained 114 active ingredients, 149 targets, and 30 common target genes with PD were obtained. The key targets included VEGFA, IL6, PTGS2, TNF, etc.; GO function enrichment analysis showed a total of 399 terms(P<0.05) were obtained, 353 of which were biological process(BP) terms, 21 were cell composition(CC) terms, and 25 were molecular function(MF) terms. In KEGG pathway enrichment analysis, 14 signaling pathways were obtained, 3 of which were related to inflammation, namely arachidonic acid metabolism, MAPK signaling pathway and NOD-like receptor signaling pathway. The compounds in Danggui Sini Decoction can play a therapeutic role in the treatment of PD by acting on VEGFA, IL-6, PTGS2, TNF and other targets to regulate arachidonic acid and inflammatory signaling pathways.

Pathological complete remission in ALK-positive lung cancer patient after multiple lines of conversion therapy.

Introduction: Traditional therapeutic approaches for the treatment of advanced non-small-cell lung cancer (NSCLC) are based on chemotherapy. However, the discovery and understanding of oncogenic driver alterations has led to the development of targeted therapies that have substantially improved patient outcomes. Still, to date, there have been no reports of patients with advanced anaplastic lymphoma kinase (ALK)-positive lung cancer achieving clinical complete response (cCR) in the systemic lesion and pathological complete remission (pCR) in primary lung lesion after multiple lines of conversion therapy. Methods: In this case, a 55-year-old man was diagnosed with ALK-positive, stage IV lung adenocarcinoma using immunohistochemistry and next generation sequencing (NGS) tests. Results: Crizotinib and two other ATP-competitive ALK inhibitors, ceritinib and alectinib, were used respectively as first-line, second-line, and third-line therapy. The patient received treatment with crizotinib and achieved partial response (PR), but 5 months later the efficacy was evaluated as progressive disease (PD). Ceritinib was used as the second-line treatment, but the disease progressed 6 months later. Alectinib was used as the third-line treatment, but the efficacy was evaluated as PD. From April 2019 to November 2019, the patient received 4 cycles of induction chemotherapy with pemetrexed/carboplatin/bevacizumab and then switched to pemetrexed/bevacizumab as the fourth-line treatment, and received the fifth line treatment, cetuximab/paclitaxel liposome/nedaplatin, for 1 cycle, but the disease still progressed. Then the patient received the sixth line of treatment, camrelizumab/lorlatinib, for 9 antitumor cycles, resulting in PR. The patient underwent surgery followed by maintenance treatment with lorlatinib and achieved cCR. To our knowledge, this is the first documented case of cCR in a patient with ALK-positive advanced lung adenocarcinoma treated with multiple lines of therapy followed by surgical treatment. Discussion: This case reveals the possible survival benefit of immunotherapy after multiple line treatment in ALK-positive advanced lung adenocarcinoma, indicating that it is possible find new therapeutic targets based on NGS molecular detection and provide precise therapeutic strategies for clinical practice when drug resistance or progression occurs in cancer therapy.

Correlation Analysis of circRNA Circ_0071662 in Diagnosis and Prognosis of Esophageal Squamous Cell Carcinoma.

BACKGROUND: The role of circRNA circ_0071662 has been studied in bladder cancer. The present study aimed to analyze its involvement in esophageal squamous cell carcinoma (ESCC). METHODS: Patients with ESCC (n = 66), esophageal ulcer (EU, n = 66), or gastroesophageal reflux disease (GERD, n = 66) and healthy controls (n = 66) were enrolled in this study. Plasma samples were collected from all patients and controls. ESCC and paired non-tumor tissue samples were collected from ESCC patients. Circ_0071662 levels in these samples were determined by RT-qPCRs. Diagnostic and prognostic values of circ_0071662 for ESCC were analyzed with ROC curve and survival curve analyses. RESULTS: Circ_0071662 level was decreased in ESCC, but not in GERN and EU compared to the controls and in ESCC tissues compared to the non-tumor tissues. Plasma circ_0071662 was closely correlated with patients' tumor size but not with other clinical features. Decreased plasma circ_0071662 levels separated ESCC patients from GERN patients, EU patients, and healthy controls. Low plasma circ_0071662 levels were closely correlated with worse survival outcomes of ESCC patients. CONCLUSION: Circ_0071662 is lowly expressed in ESCC and may serve as a potential diagnostic and prognostic biomarker for ESCC.

1-(4-Benz-yloxy-5-meth-oxy-2-nitro-phen-yl)ethanone.

In the mol-ecule of the title compound, C(16)H(15)NO(5), the aromatic rings are oriented at a dihedral angle of 74.89 (3)°. Intra-molecular C-H⋯O inter-actions result in the formation of a seven-membered ring. In the crystal structure, weak inter-molecular C-H⋯O inter-actions link the mol-ecules into chains along the b axis.

High expression of c-Met and EGFR is associated with poor survival of patients with glottic laryngeal squamous cell carcinoma.

The present study was undertaken to explore the association between the expression of hepatocyte growth factor receptor (c-Met) and epidermal growth factor receptor (EGFR) with clinicopathological factors and survival status, to obtain prognostic biomarkers in patients with glottis laryngeal squamous cell carcinoma (GLSCC). The expression status of c-Met and EGFR protein was analyzed in 71 archival laryngeal cancer samples by immunohistochemistry. Statistical methods, including univariate and multivariate Cox regression analysis, were used to determine risk factors of progression. In addition, survival analysis was performed by the Kaplan-Meier method. The present study detected positive expression of c-Met and EGFR in 69.0 and 91.5% of GLSCC samples, respectively. The median disease-free survival (DFS) and overall survival (OS) times of all patients were 42.4 and 81.8 months, respectively, and the 2-year DFS and OS rates were 60.1 and 84.91%, respectively. Univariate Cox regression analysis revealed that patients with high expression of EGFR or c-Met had a predisposition for tumor recurrence. The expression of c-Met expression was significantly associated with that of EGFR (P=0.001). High expression of c-Met or EGFR was associated with shorter DFS and OS times. Findings of the multivariate Cox regression analysis indicated that c-Met-expression may be used as an independent predictor of DFS and OS (P=0.002 and P=0.008, respectively). However, EGFR expression was not an independent predictor for DFS and OS (P=0.352 and P=0.24, respectively). The high expression of c-Met and EGFR was associated with poor survival and are important predictors for prognosis of patients with GLSCC.

EGFR mutation status in plasma and tumor tissues in non-small cell lung cancer serves as a predictor of response to EGFR-TKI treatment.

OBJECTIVE: Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) can effectively control non-small cell lung cancer (NSCLC). Therefore, EGFR mutations should be detected before lung cancer patients undergo EGFR-TKI therapy. This study assessed the feasibility and predictive value of EGFR mutations in peripheral blood samples. METHODS: EGFR mutations in exons 19 and 21 were analyzed in tumor tissue and plasma DNA samples from 121 NSCLC patients using amplification refractory mutation system (ARMS) and the integrated technique of mutant enriched PCR (me-PCR) and denaturing high performance liquid chromatography (DHPLC), respectively. RESULTS: EGFR mutations were detected in 36.4% of tumor tissues and 34.7% of the plasma at a concordance rate of 85.1% (103/121). The sensitivity and specificity of plasma EGFR mutations were 77.3% and 89.6%, respectively. The gender and tumor histology of patients served as independent predictors of EGFR mutations in both tumor tissues and plasma, while CEA level was an independent predictor of EGFR mutations in the plasma. Furthermore, EGFR-TKI treatment showed a significantly higher objective response rate (ORR), median progression-free survival (mPFS), and overall survival (mOS) in patients harboring EGFR mutation than those that did not exhibit EGFR mutation (ORR: 69.4% versus 13.0% in tissues, P < 0.001; 64.5 % vs. 28.6% in the plasma, P = 0.006. mPFS: 10.4 months versus 4.1 months in tissues, P<0.001; 10.5 months vs. 5.2 months in the plasma, P=0.001. mOS: 25.7 months versus 8.3 months in tissues, P=0.005; 25.7 months vs. 13.5 months in the plasma, P=0.038). CONCLUSIONS: EGFR mutations can be detected in the plasma using the integrated technique of me-PCR and DHPLC, which enables us to predict patient response to EGFR-TKI therapy. High serum CEA levels served as an independent predictor for plasma EGFR mutations.