Biomolecules最新文献

Naturally sourced biomolecules and their derivatives have had significant historical impacts in terms of their biomedical application [...].

Bacterial Lysates are immunostimulants clinically prescribed for the prevention of respiratory tract infections (RTIs). It has been shown that Bacterial Lysates upregulate the immune system, acting both on innate and adaptive reactions. In fact, there are demonstrations of their efficacy in restoring the integrity and immune function of epithelial barriers, activating ILC3 and dendritic cells with an enhanced Th1 response, and producing serum IgG and serum and salivary IgA specific to the administered bacterial antigens. The activated immune system also protects against other bacteria and viruses due to a trained immunity effect. Most studies show that the number of RTIs and their severity decrease in Bacterial Lysates-pretreated patients, without relevant side effects. The Bacterial Lysates treatment, in addition to reducing the number of RTIs, also prevents the deterioration of the underlying disease (i.e., COPD) induced by repeated infections. Despite these positive data, the most recent meta-analyses evidence the weakness of the studies performed, which are of low quality and have an inadequate number of patients, some of which were non-randomized while others were without a control group or were performed contemporarily in different clinical conditions or with different ages. The high heterogeneity of the studies does not allow us to state Bacterial Lysates' effectiveness in preventing RTIs with sufficient certainty. To completely define their indications, double-blind, placebo-controlled, multicenter, randomized clinical trials should be performed for each product and for each indication. The study population should be adequate for each indication. For this purpose, an adequate run-in phase will be necessary.

Repeating sequences of DNA, or repetitive elements (REs), are common features across both prokaryotic and eukaryotic genomes. Unlike many of their protein-coding counterparts, the functions of REs in host cells remained largely unknown and have often been overlooked. While there is still more to learn about their functions, REs are now recognized to play significant roles in both beneficial and pathological processes in their hosts at the cellular and organismal levels. Therefore, in this review, we discuss the various types of REs and review what is known about their evolution. In addition, we aim to classify general mechanisms by which REs promote processes that are variously beneficial and harmful to host cells/organisms. Finally, we address the emerging role of REs in cancer, aging, and neurological disorders and provide insights into how RE modulation could provide new therapeutic benefits for these specific conditions.

Petit vert (scientific name: Brassica oleracea var. gemmifera DC. × Brassica oleracea var. acephala DC.) is a new variety of vegetable created by crossbreeding kale and brussel sprouts (Brassica oleracea species). The present study aimed to identify biologically active compounds in extracts of the outer leaves of Petit vert by purification and to examine their biological activities. The dried and powdered outer leaves of Petit vert were extracted, fractionated, and purified to isolate active compounds. Mass spectrometry (MS) was used to identify the compounds, and nuclear magnetic resonance (NMR) spectroscopy was performed to elucidate their structures. The compounds isolated from Petit vert leaves were glycosides that contained kaempferol, quercetin (flavonol), or sinapic acid (phenylpropanoid). Glucose uptake in cultured C2C12 murine myoblasts in the absence of insulin was significantly increased by these compounds, kaempferol, sinapic acid, and ferulic acid, while uptake in the presence of insulin was also significantly increased by compounds 3 and 4, kaempferol, and sinapic acid. The effect was not necessarily concentration-dependent, and some agents decreased the glucose uptake at higher concentrations. The present study reports for the first time the isolation of five compounds containing sinapic acid from the outer leaves of Petit vert and their stimulation of glucose uptake in cultured C2C12 murine myoblasts. The results obtained herein suggest the potential of these compounds to effectively attenuate hyperglycemia and maintain muscle strength by promoting glucose metabolism in muscle cells.

RNA-protein complexes play a crucial role in cellular functions, providing insights into cellular mechanisms and potential therapeutic targets. However, experimental determination of these complex structures is often time-consuming and resource-intensive, and it rarely yields high-resolution data. Many computational approaches have been developed to predict RNA-protein complex structures in recent years. Despite these advances, achieving accurate and high-resolution predictions remains a formidable challenge, primarily due to the limitations inherent in current RNA-protein scoring functions. These scoring functions are critical tools for evaluating and interpreting RNA-protein interactions. This review comprehensively explores the latest advancements in scoring functions for RNA-protein docking, delving into the fundamental principles underlying various approaches, including coarse-grained knowledge-based, all-atom knowledge-based, and machine-learning-based methods. We critically evaluate the strengths and limitations of existing scoring functions, providing a detailed performance assessment. Considering the significant progress demonstrated by machine learning techniques, we discuss emerging trends and propose future research directions to enhance the accuracy and efficiency of scoring functions in RNA-protein complex prediction. We aim to inspire the development of more sophisticated and reliable computational tools in this rapidly evolving field.

Bacillus sp. G2112, an isolate from cucumber plants that inhibited plant pathogens, produces not only surfactins, iturins, and fengycins common to many Bacillus spp., but also a large variety of N-acyl-(depsi)peptides related to A-3302-B and nobilamides. Four known and fourteen previously unreported nobilamide peptides were characterized using high-resolution mass spectrometry, tandem mass spectrometry, and NMR. The stereochemistry of the amino acids of nobilamide peptides was determined using Marfey's method. The diversity of nobilamide peptides from Bacillus sp. G2112 resulted from the incorporation of different acyl groups and amino acids in the sequence. The peptides occur in linear or cyclic form. In addition, a truncated N-acetylpentapeptide was produced. Agar diffusion assays with selected nobilamide peptides against plant pathogens and human pathogens revealed that A-3302-B and its N-acyl homologs, A-3302-A and nobilamide J, exhibited powerful antibiotic activity (at 5 µg/hole) against Lysinibacillus sphaericus that can cause severe sepsis and bacteremia in patients. Moreover, nobilamide peptides from Bacillus sp. G2112 strongly promoted biofilm formation in the Gram-positive Mycobacterium aurum and Gram-negative pseudomonads. Structurally diverse nobilamides from Bacillus sp. G2112, whether linear or cyclic, penta and heptapeptides, induced biofilm formation, suggesting that the common N-acetyl-D-Phe-D-Leu-L-Phe-D-allo-Thr-L-Val amino acid sequence motif is important for the biofilm-inducing activity.

Exosomes are cell-derived, membrane-surrounded particles that deliver bioactive molecules to various cells. Due to their small size, low immunogenicity, extended blood circulation, and involvement in cellular communication, they hold potential as effective drug carriers. Exosomes are present in various biological fluids, including mare's milk, a traditional drink in Central Asia. This study aims to compare exosome isolation methodologies and determine the stability of mare's milk-derived exosomes as potential therapeutic carriers. Three extraction methods-immunoprecipitation, size exclusion chromatography, and total exosome isolation-were compared in terms of exosome characteristics, purity, and content. The isolated exosomes were then loaded with quercetin, and their ability to increase its bioavailability was tested in vitro and in vivo. Total exosome isolation was identified as the most efficient method for producing high-quality exosomes. These exosomes were loaded with quercetin and compared to free quercetin and exosomes alone. Exosomes loaded with 80 µM quercetin significantly restored β-galactosidase activity and cellular viability in doxorubicin-treated cells, exhibiting similar potency to 160 µM free quercetin. In aged model animals, treatment with quercetin-loaded exosomes resulted in significantly less acute and subacute damage to the myocardium, kidneys, and liver compared to untreated control animals. This study provides a proof-of-concept that mare's milk-derived exosomes can be effectively absorbed by cells and animal tissues, supporting their potential use as drug carriers.

Tropomyosins (Tpms) are rod-shaped proteins that interact head-to-tail to form a continuous polymer along both sides of most cellular actin filaments. Head-to-tail interaction between adjacent Tpm molecules and the formation of an overlap complex between them leads to the assembly of actin filaments with one type of Tpm isoform in time and space. Variations in the affinity of tropomyosin isoforms for different actin structures are proposed as a potential sorting mechanism. However, the detailed mechanisms of the spatio-temporal sorting of Tpms remain elusive. In this study, we investigated the early intermediates during actin-tropomyosin filament assembly, using a skeletal/cardiac Tpm isoform (Tpm1.1) and a cytoskeletal isoform (Tpm1.6) that differ only in the last 27 amino acids. We investigated how the muscle isoform Tpm1.1 and the cytoskeletal isoform Tpm1.6 nucleate domains on the actin filament, and tested whether (1) recruitment is affected by the actin isoform (muscle vs. cytoskeletal) and (2) whether there is specificity in recruiting the same isoform to a domain at these early stages. To address these questions, actin filaments were exposed to low concentrations of fluorescent tropomyosins in solution. The filaments were immobilized onto glass coverslips and the pattern of decoration was visualized by TIRF microscopy. We show that at the early assembly stage, tropomyosins formed multiple distinct fluorescent domains (here termed "cluster") on the actin filaments. An automated image analysis algorithm was developed and validated to identify clusters and estimate the number of tropomyosins in each cluster. The analysis showed that tropomyosin isoform sorting onto an actin filament is unlikely to be driven by a preference for nucleating on the corresponding muscle or cytoskeletal actin isoforms, but rather is facilitated by a higher probability of incorporating the same tropomyosin isoforms into an early assembly intermediate. We showed that the 27 amino acids at the end of each tropomyosin seem to provide enough molecular information for the attachment of the same tropomyosin isoforms adjacent to each other on an actin filament. This results in the formation of homogeneous clusters composed of the same isoform rather than clusters with mixed isoforms.

Water deficit is a major cause of yield loss for maize (Zea mays), leading to ovary abortion when applied at flowering time. To help understand the mechanisms involved in this phenomenon, the proteome response to water deficit has been analysed in developing ovaries at the silk emergence stage and five days later. Differential analysis, abundance pattern clustering and co-expression networks were performed in order to draw a general picture of the proteome changes all along ovary development and under the effect of water deficit. The results show that even mild water deficit has a major impact on ovary proteome, but this impact is very different from a response to stress. A part of the changes can be related to a slowdown of ovary development, while another part cannot. In particular, ovaries submitted to water deficit show an increase in proteins involved in protein biosynthesis and in vesicle transport together with a decrease in proteins involved in amino acid metabolism and proteolysis. According to the functions of increased proteins, the changes may be linked to auxin, brassinosteroids and jasmonate signalling but not abscisic acid.

Caenorhabditis elegans (C. elegans) has emerged as an outstanding model organism for investigating the aging process due to its shortened lifespan, well-defined genome, and accessibility of potent genetic tools. This review presents the current findings on chronological aging and photoaging in C. elegans, exploring the elaborate molecular pathways that control these processes. The progression of chronological aging is characterized by a gradual deterioration of physiological functions and is influenced by an interaction of genetic and environmental factors, including the insulin/insulin-like signaling (IIS) pathway. In contrast, photoaging is characterized by increased oxidative stress, DNA damage, and activation of stress response pathways induced by UV exposure. Although the genetic mechanisms of chronological aging in C. elegans have been characterized by extensive research, the pathways regulating photoaging are comparatively less well-studied. Here, we provide an overview of the current understanding of aging research, including the crucial genes and genetic pathways involved in the aging and photoaging processes of C. elegans. Understanding the complex interactions between these factors will provide invaluable insights into the molecular mechanisms underlying chronological aging and photoaging and may lead to novel therapeutic approaches and further studies for promoting healthy aging in humans.