The Development of Peptide-based Antimicrobial Agents against Dengue Virus.

Dengue fever has become an imminent threat to international public health because of global warming and climate change. The World Health Organization proclaimed that more than 50% of the world's population is at risk of dengue virus (DENV) infection. Therefore, developing a clinically approved vaccine and effective therapeutic remedy for treating dengue fever is imperative. Peptide drug development has become a novel pharmaceutical research field. This article reviews various peptidesbased antimicrobial agents targeting three pathways involved in the DENV lifecycle. Specifically, they are peptide vaccines from immunomodulation, peptide drugs that inhibit virus entry, and peptide drugs that interfere with viral replication. Many antiviral peptide studies against DENV have been conducted in animal model trials, and progression to clinical trials for these promising peptide drugs is anticipated.

Drug delivery systems and combination therapy by using vinca alkaloids.

Developing new methods for chemotherapy drug delivery has become a topic of great concern. Vinca alkaloids are among the most widely used chemotherapy reagents for tumor therapy; however, their side effects are particularly problematic for many medical doctors. To reduce the toxicity and enhance the therapeutic efficiency of vinca alkaloids, many researchers have developed strategies such as using liposome-entrapped drugs, chemical- or peptide-modified drugs, polymeric packaging drugs, and chemotherapy drug combinations. This review mainly focuses on the development of a vinca alkaloid drug delivery system and the combination therapy. Five vinca alkaloids (eg, vincristine, vinblastine, vinorelbine, vindesine, and vinflunine) are reviewed.

Structures of two elapid snake venom metalloproteases with distinct activities highlight the disulfide patterns in the D domain of ADAMalysin family proteins.

The structures of snake venom metalloproteases (SVMPs) are proposed to be useful models to understand the structural and functional relationship of ADAM (a disintegrin and metalloprotease) which are membrane-anchored proteins involved in multiple human diseases. We have purified, sequenced and determined the structures of two new P-III SVMPs - atragin and kaouthiagin-like (K-like) from Naja atra. Atragin exhibits a known C-shaped topology, whereas K-like adopts an I-shaped conformation because of the distinct disulfide pattern in the disintegrin-like (D) domain. K-like exhibits an enzymatic specificity toward pro-TNFalpha with less inhibition of cell migration, but atragin shows the opposite effect. The specificity of the enzymatic activity is indicated to be dominated mainly by the local structures of SVMP in the metalloprotease (M) domain, whereas the hyper-variable region (HVR) in the cysteine-rich (C) domain is involved in a cell-migration activity. We demonstrate also a pH-dependent enzymatic activity of atragin that we correlate with the structural dynamics of a Zn(2+)-binding motif and the Met-turn based on the structures determined with a pH-jump method. The structural variations between the C- and I-shapes highlight the disulfide bond patterns in the D domain of the ADAM/adamalysin/reprolysins family proteins.

Regenerative thermal oxidation of airborne N, N-dimethylformamide and its associated nitrogen oxides formation characteristics.

In this study, a two-bed electrically heated regenerative thermal oxidizer (RTO) was used to test the thermal destruction and oxides of nitrogen (NOx) formation characteristics in burning airstreams that contain either N, N-dimethylformamide or dimethylformamide (DMF) mixed with methyl ethyl ketone (MEK). The RTO contained two 0.152 m x 0.14 m x 1 m (L x W times] H) beds, both packed with gravel particles with an average diameter of approximately 0.0111 m and a height of up to 1 m with a void fraction of 0.42 in the packed section. The thermal recovery efficiency (TRE) and the gas pressure drop over the beds were also studied. Experimental results reveal that, with a valve shifting time (ts) of 1.5 min, a superficial gas velocity (Ug) of 0.39 m/sec (evaluated at an influent air temperature of around 30 degrees C) and preset maximum destruction temperatures (Ts) of 750-950 degrees C, no NOx was present in the effluent gas from the RTO when it was loaded with DMF-free air. When only DMF was present in the influent air, the average destruction efficiencies exceeded 96%, and increased with the influent DMF concentration from 300 to 750 mg/N x m3. The "NOx-N formation/DMF-N destruction" mass ratios were in the range 0.76-1.05, and decreased as the influent DMF concentration increased within the experimental range. When both DMF and MEK were present in the influent gas, the NO, formation ratio was almost the same and the DMF destruction efficiency increased with the influent MEK/DMF ratio from 150/300 to 4500/300 (mg/mg) and in the preset temperature range. The NOx formation ratios were in the range 0.75-0.96. The TRE decreased as Ug increased but was invariant with Ts. The Ergun equation was found to suffice in the estimation of the pressure drop when the gas flowed over the packing beds.