Modulatory effect of nicotinic acid on the metabolism of Caco-2 cells exposed to IL-1β and LPS

Inflammatory bowel diseases (IBD) are the most common gastrointestinal inflammatory pathologies. Previous work evidenced a lower content of nicotinic acid (NA) in feces of IBD patients compared to healthy subjects. In the present study, we aimed to understand the effects of NA on intestinal inflammation, as several studies reported its possible beneficial effect, and investigate its influence on inflammation-driven metabolism. NA was tested on a Caco-2 in-vitro model in which inflammation was induced with interleukin-1β (IL-1β) and lipopolysaccharide (LPS), two mayor proinflammatory compounds produced in IBD, that stimulate the production of cytokines, such as interleukin 8. A metabolomics approach, with gas chromatography–mass spectrometry (GC-MS) and nuclear proton magnetic resonance (1H-NMR), was applied to study the metabolic changes. The results showed that NA significantly reduced the level of IL-8 produced in both LPS and IL-1β stimulated cells, confirming the anti-inflammatory effect of NA also on intestinal inflammation. Moreover, it was demonstrated that NA treatment had a restoring effect on several metabolites whose levels were modified by treatments with IL-1β or LPS. This study points out a possible use of NA as anti-inflammatory compound and might be considered as a promising starting point in understanding the beneficial effect of NA in IBD

Bichromonol, a dimeric coumarin with anti-HIV activity from the stem bark of Hypericum roeperianum

Infectious diseases caused by viruses like HIV and SARS-COV-2 (COVID-19) pose serious public health threats. In search for new antiviral small molecules from chemically underexplored Hypericum species, a previously undescribed atropisomeric C8-C8’ linked dimeric coumarin named bichromonol (1) was isolated from the stem bark of Hypericum roeperianum. The structure was elucidated by MS data and NMR spectroscopy. The absolute configuration at the biaryl axis was determined by comparing the experimental ECD spectrum with those calculated for the respective atropisomers. Bichromonol was tested in cell-based assays for cytotoxicity against MT-4 (CC50 = 54 µM) cells and anti-HIV activity in infected MT-4 cells. It exhibits significant activity at EC50 = 6.6–12.0 µM against HIV-1 wild type and its clinically relevant mutant strains. Especially, against the resistant variants A17 and EFVR, bichromonol is more effective than the commercial drug nevirapine and might thus have potential to serve as a new anti-HIV lead

DESIGNING OF A RT REAL TIME PCR ASSAY BASED ON NS1 GENE FOR RAPID DETECTION OF USUTU VIRUS (USUV)

Introduction: Usutu virus belongs to the Japanese encephalitis virus group (the isolates exhibited 97% identity) within the family Flaviviridae closely related to West Nile virus (WNV). Both share in nature an enzootic infectious cycle between avian hosts and mosquito vectors (i.e. Culex spp.). The distribution areal is expanding in several European countries, including Italy; the simultaneous spatial and temporal co-circulation of new flaviviruses require a new approaches in the laboratory diagnosis for Flaviviridae infection in humans

Information heat engine: converting information to energy by feedback control

In 1929, Leo Szilard invented a feedback protocol in which a hypothetical intelligence called Maxwell's demon pumps heat from an isothermal environment and transduces it to work. After an intense controversy that lasted over eighty years; it was finally clarified that the demon's role does not contradict the second law of thermodynamics, implying that we can convert information to free energy in principle. Nevertheless, experimental demonstration of this information-to-energy conversion has been elusive. Here, we demonstrate that a nonequilibrium feedback manipulation of a Brownian particle based on information about its location achieves a Szilard-type information-energy conversion. Under real-time feedback control, the particle climbs up a spiral-stairs-like potential exerted by an electric field and obtains free energy larger than the amount of work performed on it. This enables us to verify the generalized Jarzynski equality, or a new fundamental principle of "information-heat engine" which converts information to energy by feedback control.Comment: manuscript including 7 pages and 4 figures and supplementary material including 6 pages and 8 figure

An experimentally-achieved information-driven Brownian motor shows maximum power at the relaxation time

We present an experimental realization of an information-driven Brownian motor by periodically cooling a Brownian particle trapped in a harmonic potential connected to a single heat bath, where cooling is carried out by the information process consisting of measurement and feedback control. We show that the random motion of the particle is rectified by symmetry-broken feedback cooling where the particle is cooled only when it resides on the specific side of the potential center at the instant of measurement. Studying how the motor thermodynamics depends on cycle period tau relative to the relaxation time tau(B) of the Brownian particle, we find that the ratcheting of thermal noise produces the maximum work extraction when tau >= 5 tau(B) while the extracted power is maximum near tau= tau(B), implying the optimal operating time for the ratcheting process. In addition, we find that the average transport velocity is monotonically decreased as tau increases and present the upper bound for the velocity

An autonomous chemically fuelled small-molecule motor

Molecular machines are among the most complex of all functional molecules and lie at the heart of nearly every biological process. A number of synthetic small-molecule machines have been developed, including molecular muscles, synthesizers, pumps, walkers, transporters and light-driven and electrically driven rotary motors. However, although biological molecular motors are powered by chemical gradients or the hydrolysis of adenosine triphosphate (ATP), so far there are no synthetic small-molecule motors that can operate autonomously using chemical energy (that is, the components move with net directionality as long as a chemical fuel is present). Here we describe a system in which a small molecular ring (macrocycle) is continuously transported directionally around a cyclic molecular track when powered by irreversible reactions of a chemical fuel, 9-fluorenylmethoxycarbonyl chloride. Key to the design is that the rate of reaction of this fuel with reactive sites on the cyclic track is faster when the macrocycle is far from the reactive site than when it is near to it. We find that a bulky pyridine-based catalyst promotes carbonate-forming reactions that ratchet the displacement of the macrocycle away from the reactive sites on the track. Under reaction conditions where both attachment and cleavage of the 9-fluorenylmethoxycarbonyl groups occur through different processes, and the cleavage reaction occurs at a rate independent of macrocycle location, net directional rotation of the molecular motor continues for as long as unreacted fuel remains. We anticipate that autonomous chemically fuelled molecular motors will find application as engines in molecular nanotechnology.</p