The emergence of carbapenem-resistant Pseudomonas aeruginosa, a multi-drug-resistant bacteria, is becoming a serious
public health concern. This bacterium infects immunocompromised patients and has a high fatality rate. Both naturally and
synthetically produced chalcones are known to have a wide array of biological activities. The antibacterial properties of
synthetically produced chalcone were studied against P. aeruginosa. In vitro, study of the compound (chalcone derivative
named DKO1), also known as (2E)-1-(5-methylfuran-2-yl)-3-(4-nitrophenyl) prop-2-en-1-one, had substantial antibacterial
and biofilm disruptive action. DKO1 effectively shielded against P. aeruginosa-induced inflammation, oxidative stress, lipid
peroxidation, and apoptosis in zebrafish larvae. In adult zebrafish, the treatment enhanced the chances of survivability and
reduced the sickness-like behaviors. Gene expression, biochemical analysis, and histopathology studies found that proinflammatory
cytokines (TNF-α, IL-1β, IL-6, iNOS) were down regulated; antioxidant enzymes such as superoxide dismutase
(SOD) and catalase (CAT) levels increased, and histoarchitecture was restored in zebrafish. The data indicate that DKO1 is
an effective antibacterial agent against P. aeruginosa demonstrated both in vitro and in vivo.
Dengue virus (DENV) consists of four serotypes in the family
Flaviviridae and is a causative agent of dengue fever, dengue
hemorrhagic fever, and dengue shock syndrome. DENV is
transmitted by mosquitoes, Aedes aegypti and A. albopictus,
and is mainly observed in areas where vector mosquitoes live.
The number of dengue cases reported by the World Health
Organization increased more than 8-fold over the last two
decades from 505,430 in 2000 to over 2.4 million in 2010 to
5.2 million in 2019. Although vaccine is the most effective method against DENV, only one commercialized vaccine exists,
and it cannot be administered to children under 9 years of
age. Currently, many researchers are working to resolve the
various problems hindering the development of effective dengue
vaccines; understanding of the viral antigen configuration
would provide insight into the development of effective
vaccines against DENV infection. In this review, the current
status and perspectives on effective vaccine development for
DENV are examined. In addition, a plausible direction for
effective vaccine development against DENV is suggested.
The poor stability of peptides against trypsin largely limits
their development as potential antibacterial agents. Here, to
obtain a peptide with increased trypsin stability and potent
antibacterial activity, TICbf-14 derived from the cationic peptide
Cbf-14 was designed by the addition of disulfide-bridged
hendecapeptide (CWTKSIPPKPC) loop. Subsequently, the
trypsin stability and antimicrobial and antibiofilm activities
of this peptide were evaluated. The possible mechanisms underlying
its mode of action were also clarified. The results
showed that TICbf-14 exhibited elevated trypsin inhibitory
activity and effectively mitigated lung histopathological damage
in bacteria-infected mice by reducing the bacterial counts,
further inhibiting the systemic dissemination of bacteria and
host inflammation. Additionally, TICbf-14 significantly repressed
bacterial swimming motility and notably inhibited
biofilm formation. Considering the mode of action, we observed
that TICbf-14 exhibited a potent membrane-disruptive
mechanism, which was attributable to its destructive effect
on ionic bridges between divalent cations and LPS of the bacterial
membrane. Overall, TICbf-14, a bifunctional peptide
with both antimicrobial and trypsin inhibitory activity, is
highly likely to become an ideal candidate for drug development
against bacteria.