Current protein & peptide science最新文献

Unconventional Post-Translational Modifications (PTMs) have gained increasing attention as crucial players in cancer development and progression. Understanding the role of unconventional PTMs in cancer has the potential to revolutionize cancer diagnosis, prognosis, and therapeutic interventions. These modifications, which include O-GlcNAcylation, glutathionylation, crotonylation, including hundreds of others, have been implicated in the dysregulation of critical cellular processes and signaling pathways in cancer cells. This review paper aims to provide a comprehensive analysis of unconventional PTMs in cancer as diagnostic markers and therapeutic targets. The paper includes reviewing the current knowledge on the functional significance of various conventional and unconventional PTMs in cancer biology. Furthermore, the paper highlights the advancements in analytical techniques, such as biochemical analyses, mass spectrometry and bioinformatic tools etc., that have enabled the detection and characterization of unconventional PTMs in cancer. These techniques have contributed to the identification of specific PTMs associated with cancer subtypes. The potential use of Unconventional PTMs as biomarkers will further help in better diagnosis and aid in discovering potent therapeutics. The knowledge about the role of Unconventional PTMs in a vast and rapidly expanding field will help in detection and targeted therapy of cancer.

Membrane protein human concentrative nucleoside transporter 3 (hCNT3) can not only transport extracellular nucleosides into the cell but also transport various nucleoside-derived anticancer drugs to the focus of infection for therapeutic effects. Typical nucleoside anticancer drugs, including fludarabine, cladabine, decitabine, and clofarabine, are recognized by hCNT3 and then delivered to the lesion site for their therapeutic effects. hCNT3 is highly conserved during the evolution from lower to higher vertebrates, which contains scaffold and transport domains in structure and delivers substrates by coupling with Na⁺ and H⁺ ions in function. In the process of substrate delivery, the transport domain rises from the lower side of transmembrane 9 (TM9) in the inward conformation to the upper side of the outward conformation, accompanied by the collaborative motion of TM7b/ TM4b and hairpin 1b (HP1b)/ HP2b. With the report of a series of three-dimensional structures of homologous CNTs, the structural characteristics and biological functions of hCNT3 have attracted increasing attention from pharmacists and biologists. Our research group has also recently designed an anticancer lead compound with high hCNT3 transport potential based on the structure of 5-fluorouracil. In this work, the sequence evolution, conservation, molecular structure, cationic chelation, substrate recognition, elevator motion pattern and nucleoside derivative drugs of hCNT3 were reviewed, and the differences in hCNT3 transport mode and nucleoside anticancer drug modification were summarized, aiming to provide theoretical guidance for the subsequent molecular design of novel anticancer drugs targeting hCNT3.

Glioblastoma multiforme (GBM) is the most common type of cancer that affects the central nervous system (CNS). It currently accounts for about 2% of diagnosed malignant tumors worldwide, with 296,000 new cases reported per year. The first-choice treatment consists of surgical resection, radiotherapy, and adjuvant chemotherapy, which increases patients' survival by 15 months. New clinical and pre-clinical research aims to improve this prognosis by proposing the search for new drugs that effectively eliminate cancer cells, circumventing problems such as resistance to treatment. One of the promising therapeutic strategies in the treatment of GBM is the inhibition of the phosphatidylinositol 3-kinase (PI3K) pathway, which is closely related to the process of tumor carcinogenesis. This review sought to address the main scientific studies of synthetic or natural drug prototypes that target specific therapy co-directed via the PI3K pathway, against human glioblastoma.

With global climate changes and the increased demand for food due to expected world population growth, genetic improvement programs have aimed at producing crops with increased yield and tolerance to environmental stresses, such as drought, salinity, and pathogens. On the other hand, genetic improvement programs via biotechnology require candidate genes that confer traits of interest to be incorporated into improved crops. In this regard, genes encoding transcription factors (TFs) can be promising since they are proteins that transcriptionally regulate the expression of target genes related to the most diverse roles in the plant, including defense against stresses. Among TFs, bZIP (basic leucine zipper) proteins regulate many developmental and physiological processes in the plant, such as seed formation, fruit ripening, nutrient assimilation, and defense response to abiotic and biotic stresses. In this review, we aim to highlight the main advances in the potential use of bZIP TFs in the genetic improvement of crops. We address this potential mainly regarding crop tolerance to stresses and other agricultural traits, such as increased yield and fruit features.

Background: Biosensors and MEMS have witnessed rapid development and enormous interest over the past decades. Constant advancement in diagnostic, medical, and chemical applications has been demonstrated in several platforms and tools. In this study, the analytical and FEA of the microcantilever used in biomolecular analyses were compared with the experimental analysis results.

Methods: In this study, MITF antigen, which is a melanoma biomarker, and anti-MITF antibody (D5) were selected as biomolecules. A MEMS-type microcantilever biosensor was designed by functionalizing the AFM cantilever by utilizing the specific interaction dynamics and intermolecular binding ability between both molecules. Surface functionalization of cantilever micro biosensors was performed by using FEA. The stress that will occur as a result of the interactions between the MITF-D5 has been determined from the deviation in the resonant frequency of the cantilever.

Results: It has been found that the simulation results are supported by analytical calculations and experimental results.

Conclusion: The fact that the results of the simulation study overlap with the experimental and mathematical results allows us to get much cheaper and faster answers compared to expensive and time-consuming experimental approaches.

Bone is a unique tissue, composed of various types of cells embedded in a calcified extracellular matrix (ECM), whose dynamic structure consists of organic and inorganic compounds produced by bone cells. The main inorganic component is represented by hydroxyapatite, whilst the organic ECM is primarily made up of type I collagen and non-collagenous proteins. These proteins play an important role in bone homeostasis, calcium regulation, and maintenance of the hematopoietic niche. Recent advances in bone biology have highlighted the importance of specific bone proteins, named "osteokines", possessing endocrine functions and exerting effects on nonosseous tissues. Accordingly, osteokines have been found to act as growth factors, cell receptors, and adhesion molecules, thus modifying the view of bone from a static tissue fulfilling mobility to an endocrine organ itself. Since bone is involved in a paracrine and endocrine cross-talk with other tissues, a better understanding of bone secretome and the systemic roles of osteokines is expected to provide benefits in multiple topics: such as identification of novel biomarkers and the development of new therapeutic strategies. The present review discusses in detail the known osseous and extraosseous effects of these proteins and the possible respective clinical and therapeutic significance.

Background: Recently, the importance of the interactions between liver cancer cells and fibroblasts has been increasingly recognized; however, many details remain to be explored.

Methods: In this work, we first studied their intercellular interactions using conditioned medium from mouse embryonic fibroblasts (MEFs), then through a previously established coculture model.

Results: Culturing in a conditioned medium from MEFs could significantly increase the growth, migration, and invasion of liver cancer cells. The coculture model further demonstrated that a positive feedback loop was formed between transforming growth factor-β (TGF-β) from HepG2 cells and mHGF (mouse hepatocyte growth factor) from MEFs during coculture. In this feedback loop, c-Met expression in HepG2 cells was significantly increased, and its downstream signaling pathways, such as Src/FAK, PI3K/AKT, and RAF/MEK/ERK, were activated. Moreover, the proportion of activated MEFs was also increased. More importantly, the growth-promoting effects caused by the interaction of these two cell types were validated in vitro by a 3D spheroid growth assay and in vivo by a xenograft mouse model.

Conclusion: Collectively, these findings provide valuable insights into the interactions between fibroblasts and liver cancer cells, which may have therapeutic implications for the treatment of liver cancer.

Metabolic disorders have long been a challenge for medical professionals and are a leading cause of mortality in adults. Diabetes, cardiovascular disorders (CVD), renal dysfunction, and ischemic stroke are the most prevalent ailments contributing to a high mortality rate worldwide. Reactive oxygen species are one of the leading factors that act as a fundamental root cause of metabolic syndrome. All of these disorders have their respective treatments, which, to some degree, sabotage the pathological worsening of the disease and an inevitable death. However, they pose a perilous health hazard to humankind. Cysteine, a functional amino acid shows promise for the prevention and treatment of metabolic disorders, such as CVD, Diabetes mellitus, renal dysfunction, and ischemic stroke. In this review, we explored whether cysteine can eradicate reactive oxygen species and subsequently prevent and treat these diseases.

Ursodeoxycholic acid (UDCA) is a natural substance physiologically produced in the liver. Initially used to dissolve gallstones, it is now successfully used in treating primary biliary cirrhosis and as adjuvant therapy for various hepatobiliary cholestatic diseases. However, the mechanisms underlying its beneficial effects still need to be clarified. Evidence suggests three mechanisms of action for UDCA that could benefit humans with cholestatic liver disease (CLD): protection of cholangiocytes against hydrophobic bile acid (BA) cytotoxicity, stimulation of hepatobiliary excretion, and protection of hepatocytes against BA-induced apoptosis. These mechanisms may act individually or together to potentiate them. At the molecular level, it has been observed that UDCA can generate modifications in the transcription and translation of proteins essential in the transport of BA, correcting the deficit in BA secretion in CLD, in addition to activating signaling pathways to translocate these transporters to the sites where they should fulfill their function. Inhibition of BA-induced hepatocyte apoptosis may play a role in CLD, characterized by BA retention in the hepatocyte. Thus, different mechanisms of action contribute to the improvement after UDCA administration in CLD. On the other hand, the effects of UDCA on tissues that possess receptors that may interact with BAs in pathological contexts, such as skeletal muscle, are still unclear. This work aims to describe the main molecular mechanisms by which UDCA acts in the human body, emphasizing the interaction in tissues other than the liver.

Cyanobacteria have emerged as a microbial cell factory to produce a variety of bioproducts, including peptides and proteins. Cyanobacteria stand out among other organisms due to their photoautotrophic metabolism and ability to produce a wide range of metabolites. As photoautotrophic hosts can produce industrial compounds and proteins by using minimal resources such as sunlight, atmospheric carbon dioxide, and fewer nutrients, cyanobacteria are cost-effective industrial hosts. Therefore, the use of protein engineering tools for rational protein design, and the desired modification of enzyme activity has become a desirable undertaking in cyanobacterial biology. Protein engineering can improve their biological functions as well as the stability of their intracellular proteins. This review aims to highlight the success of protein engineering in the direction of cyanobacterial biotechnology and outlines the emerging technologies, current challenges, and prospects of protein engineering in cyanobacterial biotechnology.