Anti-HIV-1 Activity of a New Scorpion Venom Peptide Derivative Kn2-7

For over 30 years, HIV/AIDS has wreaked havoc in the world. In the absence of an effective vaccine for HIV, development of new anti-HIV agents is urgently needed. We previously identified the antiviral activities of the scorpion-venom-peptide-derived mucroporin-M1 for three RNA viruses (measles viruses, SARS-CoV, and H5N1). In this investigation, a panel of scorpion venom peptides and their derivatives were designed and chosen for assessment of their anti-HIV activities. A new scorpion venom peptide derivative Kn2-7 was identified as the most potent anti-HIV-1 peptide by screening assays with an EC50 value of 2.76 µg/ml (1.65 µM) and showed low cytotoxicity to host cells with a selective index (SI) of 13.93. Kn2-7 could inhibit all members of a standard reference panel of HIV-1 subtype B pseudotyped virus (PV) with CCR5-tropic and CXCR4-tropic NL4-3 PV strain. Furthermore, it also inhibited a CXCR4-tropic replication-competent strain of HIV-1 subtype B virus. Binding assay of Kn2-7 to HIV-1 PV by Octet Red system suggested the anti-HIV-1 activity was correlated with a direct interaction between Kn2-7 and HIV-1 envelope. These results demonstrated that peptide Kn2-7 could inhibit HIV-1 by direct interaction with viral particle and may become a promising candidate compound for further development of microbicide against HIV-1

All-Dielectric Surface-Enhanced Infrared Absorption-Based Gas Sensor Using Guided Resonance

10.1021/acsami.8b16623ACS APPLIED MATERIALS & INTERFACES104438272-3827

Genome-wide methylation profiling identify hypermethylated HOXL subclass genes as potential markers for esophageal squamous cell carcinoma detection

Abstract Background Numerous studies have revealed aberrant DNA methylation in esophageal squamous cell carcinoma (ESCC). However, they often focused on the partial genome, which resulted in an inadequate understanding of the shaped methylation features and the lack of available methylation markers for this disease. Methods The current study investigated the methylation profiles between ESCC and paired normal samples using whole-genome bisulfite sequencing (WGBS) data and obtained a group of differentially methylated CpGs (DMC), differentially methylated regions (DMR), and differentially methylated genes (DMG). The DMGs were then verified in independent datasets and Sanger sequencing in our custom samples. Finally, we attempted to evaluate the performance of these genes as methylation markers for the classification of ESCC. Results We obtained 438,558 DMCs, 15,462 DMRs, and 1568 DMGs. The four significantly enriched gene families of DMGs were CD molecules, NKL subclass, HOXL subclass, and Zinc finger C2H2-type. The HOXL subclass homeobox genes were observed extensively hypermethylated in ESCC. The HOXL-score estimated by HOXC10 and HOXD1 methylation, whose methylation status were then confirmed by sanger sequencing in our custom ESCC samples, showed good ability in discriminating ESCC from normal samples. Conclusions We observed widespread hypomethylation events in ESCC, and the hypermethylated HOXL subclass homeobox genes presented promising applications for the early detection of esophageal squamous cell carcinoma

Engineering BPQDs/PLGA nanospheres-integrated wood hydrogel bionic scaffold for combinatory bone repair and osteolytic tumor therapy

Bone regeneration following the removal of tumor tissues remains a major clinical challenge for the treatment of bone defects, in which materials with combinatory bone repair and osteolytic metastasis therapy is considered as a promising solution. Herein, a highly strong delignified wood/regenerated silk fibroin (RSF) hydrogel scaffold integrated with black phosphorus quantum dots (BPQDs) encapsulated by poly (lactic-co-glycolic acid) (PLGA) was engineered to realize efficient mechanical supporting, bone regeneration, and tumor therapy. Following delignification, the white wood (WW) scaffold significantly improved the mechanical properties of RSF composite hydrogel, with the elastic modulus in the L-direction and R-direction of 300 MPa and 3.3 MPa, and compression modulus in the L-direction of 9.3 MPa. Moreover, the WW/RSF hydrogel scaffold with BPQD/PLGA nanospheres effectively promoted the proliferation, migration, and osteogenic differentiation of bone mesenchymal stem cells and enhanced osteogenesis in vivo. Compared with the vertical implantation method, better bone regeneration was observed in parallel implantation system parallel to bone shaft. Importantly, the BPQDs in the hydrogel scaffolds could inhibit osteoclast differentiation and exhibit photothermal effects against metastatic tumor in the spine. Our data provide promising evidence for the potential therapeutic application on bone regeneration and ablation of bone metastasis.</p

Unpolarized release of vaccinia virus and HIV antigen by colchicine treatment enhances intranasal HIV antigen expression and mucosal humoral responses.

The induction of a strong mucosal immune response is essential to building successful HIV vaccines. Highly attenuated recombinant HIV vaccinia virus can be administered mucosally, but even high doses of immunization have been found unable to induce strong mucosal antibody responses. In order to solve this problem, we studied the interactions of recombinant HIV vaccinia virus Tiantan strain (rVTT-gagpol) in mucosal epithelial cells (specifically Caco-2 cell layers) and in BALB/c mice. We evaluated the impact of this virus on HIV antigen delivery and specific immune responses. The results demonstrated that rVTT-gagpol was able to infect Caco-2 cell layers and both the nasal and lung epithelia in BALB/c mice. The progeny viruses and expressed p24 were released mainly from apical surfaces. In BALB/c mice, the infection was limited to the respiratory system and was not observed in the blood. This showed that polarized distribution limited antigen delivery into the whole body and thus limited immune response. To see if this could be improved upon, we stimulated unpolarized budding of the virus and HIV antigens by treating both Caco-2 cells and BALB/c mice with colchicine. We found that, in BALB/c mice, the degree of infection and antigen expression in the epithelia went up. As a result, specific immune responses increased correspondingly. Together, these data suggest that polarized budding limits antigen delivery and immune responses, but unpolarized distribution can increase antigen expression and delivery and thus enhance specific immune responses. This conclusion can be used to optimize mucosal HIV vaccine strategies