The tissue accumulation of advanced glycation end products (AGEs) can be noninvasively assessed as skin autofluorescence (SAF) by the AGE Reader(TM) device. We aimed to detect the association between SAF and diabetes-associated vascular complications in diabetic foot ulcer (DFU) patients engaged in this study. This cross-sectional survey consisted of 118 consecutive hospitalized diabetic foot patients. The diabetic microvascular (retinopathy, nephropathy, and neuropathy) and macrovascular referring to coronary heart disease (CHD), cerebrovascular disease (CVD), or peripheral artery disease (PAD) complications were evaluated, and then they were divided into different subgroups based on the assessment of vascular complications. As seen from the results, the mean SAF value was 2.8 ± 0.2 AU. SAF was significantly associated with diabetes duration and blood urea nitrogen (R(2) = 62.8%; P < .01). Moreover, in logistic regression analysis, SAF was significantly associated with retinopathy (odds ratio [OR] = 40.11), nephropathy (OR = 8.44), CHD (OR = 44.31), CVD (OR = 80.73), and PAD (OR = 5.98 × 10(9)). In conclusion, SAF, reflecting tissue accumulation of AGEs, is independently associated with the presence of vascular complications in DFU patients.
Thioflavin T (ThT) was once regarded to be a specific fluorescent probe for the human telomeric G-quadruplex, but more other kinds of DNA were found that can also bind to ThT in recent years. Herein, we focus on G-rich parallel-stranded DNA and utilize fluorescence, absorbance, circular dichroism, and surface plasmon resonance spectroscopy to investigate its interaction with ThT. Pyrene label and molecular modeling are applied to unveil the binding mechanism. We find a new class of non-G-quadruplex G-rich parallel-stranded ( ps) DNA with the sequence of TG(GA) n can bind to ThT and increase the fluorescence with an enhancement ability superior to G-quadruplex. The optimal binding specificity for ThT is conferred by two parts. The first part is composed of two bases TG at the 5' end, which is a critical domain and plays an important role in the formation of the binding site for ThT. The second part is the rest alternative d(GA) bases, which forms the ps homoduplex and cooperates with the TG bases at the 5' end to bind the ThT.
Staphylococcus aureus
(
S. aureus
) is one of the most serious human pathogens. α-Hemolysin (Hla) secreted by
S. aureus
is a key toxin for various infections. We herein report that Honokiol, a natural plant polyphenol, inhibits the secretion and hemolytic activity of staphylococcal Hla with concomitant growth inhibition of
S. aureus
and protection of
S. aureus
-mediated cell injury within subinhibitory concentrations. In parallel, Honokiol attenuates the staphylococcal Hla-induced inflammatory response by inhibiting NLRP3 inflammasome activation
in vitro
and
in vivo
. Consequently, the biologically active forms of the inflammatory cytokines IL-1
β
and IL-18 are reduced significantly in response to Honokiol in mice infected with
S. aureus
. Experimentally, we confirm that Honokiol binds to monomeric Hla with a modest affinity without impairing its oligomerization. Based on molecular docking analyses
in silico
, we make a theoretical discovery that Honokiol is located outside of the triangular region of monomeric Hla. The binding model restricts the function of the residues related to membrane channel formation, which leads to the functional disruption of the assembled membrane channel. This research creates a new paradigm for developing therapeutic agents against staphylococcal Hla-mediated infections.
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