Mining Translation Inhibitors by a Unique Peptidyl-Aminonucleoside Synthetase Reveals Cystocin Biosynthesis and Self-Resistance.

Puromycin (Puro) is a natural aminonucleoside antibiotic that inhibits protein synthesis by its incorporation into elongating peptide chains. The unique mechanism of Puro finds diverse applications in molecular biology, including the selection of genetically engineered cell lines, in situ protein synthesis monitoring, and studying ribosome functions. However, the key step of Puro biosynthesis remains enigmatic.

Imaging-based profiling for elucidation of antibacterial mechanisms of action.

In this review, we aim to summarize experimental data and approaches to identifying cellular targets or mechanisms of action of antibacterials based on imaging techniques. Imaging-based profiling methods, such as bacterial cytological profiling, dynamic bacterial morphology imaging, and others, have become a useful research tool for mechanistic studies of new antibiotics as well as combinations with conventional ones and other therapeutic options. The main methodological and experimental details and obtained results are summarized and discussed.

Reformulation of Time-Dependent Density Functional Theory for Nonperturbative Dynamics: The Rabi Oscillation Problem Resolved.

Rabi oscillations have long been thought to be out of reach in simulations using time-dependent density functional theory (TDDFT), a prominent symptom of the failure of the adiabatic approximation for nonperturbative dynamics. We present a reformulation of TDDFT which requires response quantities only, thus enabling an adiabatic approximation to predict such dynamics accurately because the functional is evaluated on a density close to the ground state, instead of on the fully nonperturbative density. Our reformulation applies to any real-time dynamics, redeeming TDDFT far from equilibrium.

Sensing of Antibiotic-Bacteria Interactions.

Sensing of antibiotic-bacteria interactions is an important area of research that has gained significant attention in recent years. Antibiotic resistance is a major public health concern, and it is essential to develop new strategies for detecting and monitoring bacterial responses to antibiotics in order to maintain effective antibiotic development and antibacterial treatment. This review summarizes recent advances in sensing strategies for antibiotic-bacteria interactions, which are divided into two main parts: studies on the mechanism of action for sensitive bacteria and interrogation of the defense mechanisms for resistant ones.

Modern Trends in Natural Antibiotic Discovery.

Natural scaffolds remain an important basis for drug development. Therefore, approaches to natural bioactive compound discovery attract significant attention. In this account, we summarize modern and emerging trends in the screening and identification of natural antibiotics.

Random Copolymers of Styrene with Pendant Fluorophore Moieties: Synthesis and Applications as Fluorescence Sensors for Nitroaromatics.

Five random copolymers comprising styrene and styrene with pendant fluorophore moieties, namely pyrene, naphthalene, phenanthrene, and triphenylamine, in molar ratios of 10:1, were synthesized and employed as fluorescent sensors. Their photophysical properties were investigated using absorption and emission spectral analyses in dichloromethane solution and in solid state. All copolymers possessed relative quantum yields up to 0.

Bicyclic Isoxazoline Derivatives: Synthesis and Evaluation of Biological Activity.

The application of non-planar scaffolds in drug design allows for the enlargement of the chemical space, and for the construction of molecules that have more effective target-ligand interactions or are less prone to the development of resistance. Among the works of the last decade, a literature search revealed spirothiazamenthane, which has served as a lead in the development of derivatives active against resistant viral strains. In this work, we studied the novel molecular scaffold, which resembles spirothiazamenthane, but combines isoxazoline as a heterocycle and cyclooctane ring as a hydrophobic part of the structure.

Triple-negative breast cancer: current treatment strategies and factors of negative prognosis.

Breast cancer is the most common cancer in women and the most common cause of death in working-age women. According to the results of immunohistochemical studies, 10-20% of cases revealed a triple-negative type of breast cancer. This subtype is characterized by significant proliferative activity and growth rate, aggressive clinical course, and early metastasis.

Optical Properties of Crystalline Lactose Fluidized with Dilutions of Various Substances in the Terahertz Frequency Range.

Lactose is a commonly used component of pharmaceutical medications in tablet form. It was previously shown that lactose changes conformationally after saturation in fluidized beds with active pharmaceutical ingredients obtained by repeated dilution of antibodies to interferon-gamma in combination with an external intensive vibration treatment. Moreover, it was revealed that these solutions are self-organized dispersed systems in which nano-objects are formed.

Gausemycins A,B: Cyclic Lipoglycopeptides from Streptomyces sp.*.

We report a novel family of natural lipoglycopeptides produced by Streptomyces sp. INA-Ac-5812. Two major components of the mixture, named gausemycins A and B, were isolated, and their structures were elucidated.

Identification of isocyclosporins by collision-induced dissociation of doubly protonated species.

Nonribosomal cyclopeptide cyclosporin A (CsA), produced by fungus Tolypocladium inflatum, is an extremely important immunosuppressive drug used in organ transplantations and for therapy of autoimmune diseases. Here we report for the first time production of CsA, along with related cyclosporins B and C, by Tolypocladium inflatum strains of marine origin (White Sea). Cyclosporins A-C contain an unusual amino acid, (4R)-4-((E)-2-butenyl)-4,N-dimethyl-l-threonine (MeBmt), and are prone to isomerization to non-active isocyclosporin by N→O acyl shift of valine connected to MeBmt in acidic conditions.

A Novel Lipopeptaibol Emericellipsin A with Antimicrobial and Antitumor Activity Produced by the Extremophilic Fungus .

Soil fungi are known to contain a rich variety of defense metabolites that allow them to compete with other organisms (fungi, bacteria, nematodes, and insects) and help them occupy more preferential areas at the expense of effective antagonism. These compounds possess antibiotic activity towards a wide range of other microbes, particularly fungi that belong to different taxonomical units. These compounds include peptaibols, which are non-ribosomal synthesized polypeptides containing non-standard amino acid residues (alpha-aminoisobutyric acid mandatory) and some posttranslational modifications.

Detection of nitroaromatic explosives by new D-π-A sensing fluorophores on the basis of the pyrimidine scaffold.

A series of D-π-A- type dyes based on pyrimidines, bearing various thiophene linkers, have been studied as sensing fluorophores. Fluorescence studies have demonstrated that the emission of all derivatives is sensitive to the presence of nitroaromatic explosives, such as 2,4,6-trinitrophenol (PA), 2,4,6-trinitrotoluene (TNT), and 2,4-dinitrotoluene (DNT), in their acetonitrile solutions. The detection limits of fluorophores to PA, TNT, and DNT proved to be in the range from 5.

The long-term microvascular and behavioral consequences of experimental traumatic brain injury after hypothermic intervention.

Traumatic brain injury (TBI) has been demonstrated to induce cerebral vascular dysfunction that is reflected in altered responses to various vasodilators. While previous reports have focused primarily on the short-term vascular alterations, few have examined these vascular changes for more than 7 days, or have attempted to correlate these alterations with any persisting behavioral changes or potential therapeutic modulation. Accordingly, we evaluated the long-term microvascular and behavioral consequences of experimental TBI and their therapeutic modulation via hypothermia.

Cerebral vascular responsiveness after experimental traumatic brain injury: the beneficial effects of delayed hypothermia combined with superoxide dismutase administration.

Object: Traumatic brain injury (TBI) induces cerebral vascular dysfunction reflected in altered responses to vasodilators such as acetylcholine and hypercapnia. It has been demonstrated that the use of either posttraumatic hypothermia or free radical scavengers offered vascular protection when those treatments were delivered early after the injury, losing efficacy when the initiation of either treatment was delayed. Because immediate posttraumatic treatment is not realistic in the clinical setting, the authors undertook this study to investigate whether the combination of delayed hypothermia and the delayed administration of the free radical scavenger superoxide dismutase (SOD) could result in improved vascular protection.

Delayed, post-injury treatment with aniracetam improves cognitive performance after traumatic brain injury in rats.

Chronic cognitive impairment is an enduring aspect of traumatic brain injury (TBI) in both humans and animals. Treating cognitive impairment in the post-traumatic stages of injury often involves the delivery of pharmacologic agents aimed at specific neurotransmitter systems. The current investigation examined the effects of the nootropoic drug aniracetam on cognitive recovery following TBI in rats.

Hepatic gene expression in patients with obesity-related non-alcoholic steatohepatitis.

Background: Non-alcoholic fatty liver disease (NAFLD) is among the most common causes of chronic liver disease. NAFLD includes a spectrum of clinicopathologic syndromes that includes non-alcoholic steatohepatitis (NASH) that has potential for progression. The pathogenesis of NASH is poorly characterized.