Biomolecular Concepts最新文献

Alzheimer's disease (AD) is characterized by immune system dysregulation, impacting both central and peripheral immune responses. The study aimed to investigate the mechanism behind the neurotoxic effects of β-amyloid (Aβ) peptide in the rat brain including the study of neuroinflammation, neurodegeneration, and alterations in peripheral immune responses (PIR). The neuroinflammation brought on by Aβ_1-42 and is unknown to influence PIR. Animal models were prepared, after 28 days, control, sham, and treated rats were anaesthetized and inflammatory markers of hippocampus and serum levels (reactive oxygen species, nitrite, tumor necrosis factor-α, and interleukin-1β), and some markers of PIR (splenic mononuclear cells or MNC, cytotoxicity and phagocytic index of the white blood cells leukocyte adhesion inhibition index or LAI), as well as polymorphonuclear cells of the spleen, were assessed. In addition to changes in peripheral immune responses, the present study found that AD rats had higher blood levels of inflammatory markers. Based on the study, the immune system irregularities observed in AD rats in the peripheral regions might be connected to neuroinflammation, which is facilitated by a compromised blood-brain barrier. Hence, it is viable to propose that the neuroinflammatory condition in rats with Aβ-induced AD could modify immune responses in the peripheral areas with significantly higher levels of inflammatory cytokines markers in the hippocampal tissue in Aβ-injected AD rats.

This study explores the synergistic antibacterial effects of essential oils (EOs) and phenolic extracts from three plants against foodborne pathogenic bacteria. The present work aimed to investigate the synergistic effects of the binary and the ternary combinations of extracts using different blend proportions of the following plant extracts: Artemisia campestris (AC), Artemisia herba alba (AHA), and Citrus aurantium (CA). The antimicrobial activities of EOs and phenolic extracts were determined and evaluated against five strains. For the EOs, the results of the DIZ showed the existence of synergism for different combinations of binary blends, such as AC/AHA or AHA/CA against Escherichia coli, and AC/CA against Enterobacter faecalis. In addition, ternary blends of AC:AHA:CA at a ratio of 1/6:2/3:1/6 exhibited a synergy effect, as measured by the CI, against E. coli. On the other hand, for the phenolic extracts, synergistic effects were noticed for binary blends of AC/CA at different ratios against E. coli, E. faecalis, and Pseudomonas aeruginosa strains. Similarly, ternary blends of phenolic extracts presented synergy against E. coli, E. faecalis, P. aeruginosa strains, and even C. albicans. In this case, the blending ratios were crucial determining factors for maximizing the synergy effect. The study established that the proportion of a single drug could play an essential role in determining the bioefficacy of a drug combination treatment. Therefore, the results showed the importance of studying the modulation of antibacterial activities based on the proportions of extracts in the mixture and finding the range of proportions (as determined by SLMD) that have a synergistic/additive/antagonistic effect with no or low side effects, which can be used in a food preservation system.

Epigenetic analysis is a fundamental part of understanding pathophysiological processes with potential applications in diagnosis, prognosis, and assessment of disease susceptibility. Epigenetic changes have been widely studied in chronic obstructive pulmonary disease (COPD), but currently, there is no molecular marker used to improve the treatment of patients. Furthermore, this progressive disease is a risk factor for the development of more severe COVID-19. Methylation-specific polymerase chain reaction (MSP-PCR) plays an important role in the analysis of DNA methylation profiles, and it is one of the most widely used techniques. In this context, the combination of MSP-PCR with emerging PCR technologies, such as digital PCR (dPCR), results in more accurate analyses of the DNA methylation profile of the genes under study. In this study, we propose the application of the MSP-dPCR technique to evaluate the methylation profile of the ADAM33 gene from saliva samples and lung tissue biopsies of patients with COPD and COVID-19. MSP-dPCR generated a measurable prediction of gene methylation rate, with the potential application of this combined technology for diagnostic and prognostic purposes. It has also proven to be a powerful tool for liquid biopsy applications.

5-Hydroxy-3',4',6,7-tetramethoxyflavone (TMF) is a plant-origin flavone known for its anti-cancer properties. In the present study, the cytotoxic effect of TMF was evaluated in the U87MG and T98G glioblastoma (GBM) cell lines. The effect of TMF on cell viability was assessed with trypan blue exclusion assay and crystal violet staining. In addition, flow cytometry was performed to examine its effect on the different phases of the cell cycle, and in vitro scratch wound assay assessed the migratory capacity of the treated cells. Furthermore, the effect of in vitro radiotherapy was also evaluated with a combination of TMF and radiation. In both cell lines, TMF treatment resulted in G0/G1 cell cycle arrest, reduced cell viability, and reduced cell migratory capacity. In contrast, there was an antagonistic property of TMF treatment with radiotherapy. These results demonstrated the antineoplastic effect of TMF in GBM cells in vitro, but the antagonistic effect with radiotherapy indicated that TMF should be further evaluated for its possible antitumor role post-radiotherapy.

In the past two decades, oxidative stress (OS) has drawn a lot of interest due to the revelation that individuals with many persistent disorders including diabetes, polycystic ovarian syndrome (PCOS), cardiovascular, and other disorders often have aberrant oxidation statuses. OS has a close interplay with PCOS features such as insulin resistance, hyperandrogenism, and chronic inflammation; there is a belief that OS might contribute to the development of PCOS. PCOS is currently recognized as not only one of the most prevalent endocrine disorders but also a significant contributor to female infertility, affecting a considerable proportion of women globally. Therefore, the understanding of the relationship between OS and PCOS is crucial to the development of therapeutic and preventive strategies for PCOS. Moreover, the mechanistic study of intracellular reactive oxygen species/ reactive nitrogen species formation and its possible interaction with women's reproductive health is required, which includes complex enzymatic and non-enzymatic antioxidant systems. Apart from that, our current review includes possible regulation of the pathogenesis of OS. A change in lifestyle, including physical activity, various supplements that boost antioxidant levels, particularly vitamins, and the usage of medicinal herbs, is thought to be the best way to combat this occurrence of OS and improve the pathophysiologic conditions associated with PCOS.

¹⁰B isotopes have been almost exclusively used in the neutron-capture radiation therapy (NCT) of cancer for decades. We have identified two other nuclides suitable for radiotherapy, which have ca. ten times larger cross section of absorption for neutrons and emit heavy charged particles. This would provide several key advantages for potential NCT, such as the possibility to use a lower nuclide concentration in the target tissues or a lower neutron irradiation flux. By detecting the characteristic γ radiation from the spontaneous decay of the radionuclides, one can image their biodistribution. These advantages could open up new possibilities for NCT applications as a safer and more efficient cancer therapy.

Diabetes mellitus is a metabolic disorder described by compromised insulin synthesis or resistance to insulin inside the human body. Diabetes is a persistent metabolic condition defined by elevated amounts of glucose in the bloodstream, resulting in a range of potential consequences. The main purpose of this study was to find out how biosynthesized copper oxide nanoparticles (CuONPs) affect the blood sugar levels of diabetic albino rats induced by streptozotocin (STZ). In the current study, CuONPs were successfully biosynthesized using Saccharomyes cervisiae using an eco-friendly method. Characterization results revealed that biosynthesized CuONPs appeared at 376 nm with a spherical shape with sizes ranging from 4 to 47.8 nm. Furthermore, results illustrated that administration of 0.5 and 5 mg/kg CuONP in diabetic rats showed a significant decrease in blood glucose levels accompanied by elevated insulin levels when compared to the diabetic control group; however, administration of 0.5 mg/kg is the best choice for diabetic management. Furthermore, it was found that the group treated with CuONPs exhibited a noteworthy elevation in the HDL-C level, along with a depletion in triglycerides, total cholesterol, LDL-C, and VLDL-cholesterol levels compared to the diabetic control group. This study found that administration of CuONPs reduced hyperglycemia and improved pancreatic function as well as dyslipidemia in diabetic rats exposed to STZ, suggesting their potential as a promising therapeutic agent for diabetes treatment.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is an RNA virus belonging to the coronavirus family responsible for coronavirus disease 2019 (COVID-19). It primarily affects the pulmonary system, which is the target of chronic obstructive pulmonary disease (COPD), for which many new compounds have been developed. In this study, phosphodiesterase 4 (PDE4) inhibitors are being investigated. The inhibition of PDE4 enzyme produces anti-inflammatory and bronchodilator effects in the lung by inducing an increase in cAMP concentrations. Piclamilast and rolipram are known selective inhibitors of PDE4, which are unfortunately endowed with common side effects, such as nausea and emesis. The selective inhibition of the phosphodiesterase 4B (PDE4B) subtype may represent an intriguing technique for combating this highly contagious disease with fewer side effects. In this article, molecular docking studies for the selective inhibition of the PDE4B enzyme have been carried out on 21 in-house compounds. The compounds were docked into the pocket of the PDE4B catalytic site, and in most cases, they were almost completely superimposed onto piclamilast. Then, in order to enlarge our study, drug-likeness prediction studies were performed on the compounds under study.

The current millennium brought up a revolutionary paradigm shift in molecular biology: many operative proteins, rather than being quasi-rigid polypeptide chains folded into unique configurations - as believed throughout most of the past century - are now known to be intrinsically disordered, dynamic, pleomorphic, and multifunctional structures with stochastic behaviors. Yet, part of this knowledge, including suggestions about possible mechanisms and plenty of evidence for the same, became available by the 1950s and 1960s to remain then nearly forgotten for over 40 years. Here, we review the main steps toward the classic notions about protein structures, as well as the neglected precedents of present views, discuss possible explanations for such long oblivion, and offer a sketch of the current panorama in this field.

Amphid wing "C" (AWC) neurons are among the most important and studied neurons of the nematode Caenorhabditis elegans. In this work, we unify the existing electrical and intracellular calcium dynamics descriptions to obtain a biophysically accurate model of olfactory transduction in AWC^ON neurons. We study the membrane voltage and the intracellular calcium dynamics at different exposure times and odorant concentrations to grasp a complete picture of AWC^ON functioning. Moreover, we investigate the complex cascade of biochemical processes that allow AWC activation upon odor removal. We analyze the behavior of the different components of the models and, by suppressing them selectively, we extrapolate their contribution to the overall neuron response and study the resilience of the dynamical system. Our results are all in agreement with the available experimental data. Therefore, we provide an accurate mathematical and biophysical model for studying olfactory signal processing in C. elegans.