Current protein & peptide science最新文献

Background: Metadoxine, also known as pyruvate dehydrogenase activator, is a small molecule drug that has been used in the treatment of various medical conditions. Bovine serum albumin is a commonly studied protein that serves as a plasmatic for understanding protein-drug interactions due to its abundance.

Objective: This research suggests that metadoxine can bind to bovine serum albumin with moderate affinity, leading to an alteration in the secondary structure of the protein, which may also influence the protein's stability and function, which could provide a comprehensive understanding of the interaction at a molecular level. In this study, a variety of methodologies wereused to determine various thermodynamic parameters.

Methods: The study uses UV-visible, Fluorescence, Fourier-transform infrared, Circular dichroism spectroscopy, and Molecular docking to analyze the interaction between bovine serum albumin and metadoxine, providing thermodynamic parameters for understanding the protein structure and its binding.

Result: The binding of metadoxine with bovine serum albumin, causes a hyperchromic shift. In fluorescence spectroscopy, the value of the Stern Volmer increases constantly with an increase in temperature, suggesting a stronger interaction between the Metadoxine and the Bovine serum albumin, leading to dynamic quenching. Additionally, Fourier-transform infrared and circular dichroism indicated a reduction in the secondary structure of Bovine serum albumin.

Conclusion: The interactions between metadoxine and bovine serum albumin, cause hyperchromic shift revealed by UV-visible spectroscopy, whereas in Fluorescence spectroscopy, the value of the Stern Volmer constant increases with an increase in temperature, suggesting a stronger interaction between the MD and the BSA, leading to dynamic quenching. Additionally, Fourier-transform infrared and circular dichroism spectroscopy indicated a reduction in the secondary structure of the protein, as evidenced by the shifting of the amide II band and leading to a slight decrease in the α- helix content. The molecular docking shows that metadoxine was docked in the subdomain IIA binding pocket of BSA.

Background: Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer with a high recurrence rate. A new therapeutic intervention is urgently needed to combat this lethal subtype. The identification of biomarkers is also crucial for improving outcomes in TNBC.

Methods: The cell cytotoxicity of ML364 (2-(4-Methylphenylsulfonamido)-N-(4-phenylthiazol- 2-yl)-4-(trifluoromethyl)benzamide) was measured at different concentrations in TNBC-treated and untreated cells. The 2DE and LC-MS/MS analysis were used for protein identification of differentially expressed proteins. Furthermore, the quantitation of gene expression was demonstrated using RT-qPCR. TIMER, HPA, and UALCAN databases were utilized for further analysis.

Results: Differentially expressed proteins and genes after ML364 treatment in TNBC were found to be linked with the USP2 (ubiquitin specific peptidase 2)-mediated pathway. Our results demonstrate that differentially identified proteins, including PPA1, TRIM68, and FBXO46, could be a potential prognostic biomarker for TNBC. Further analysis through the UALCAN and HPA databases shows the high expression of these proteins in primary breast tumors, which is in contrast to normal. The induction of ML364 significantly reduced the expression of PPA1, TRIM68, and FBXO46 proteins and induced cell cytotoxicity in TNBC cells.

Conclusion: This study provides an understanding of the USP2-mediated signaling pathway in TNBC, emphasizing the role of USP2 and its substrates with apoptotic genes. Our results offer insight into the USP2-mediated cellular mechanism after ML364 treatment in TNBC that could be a potential therapeutic candidate.

Stroke is an acute cerebrovascular disease that causes brain tissue damage due to sudden blockage or rupture of blood vessels in the brain. According to the latest data from the Global Burden of Disease Study, the number of stroke patients worldwide is estimated to exceed 100 million, and more than 80% of patients suffer from stroke. Ischemic stroke is a type of stroke due to which two-thirds of the patients are disabled or even die, seriously affecting the patient's quality of life. Lactate is an indispensable substance in various physiological and pathological cells and plays a regulatory role in different aspects of energy metabolism and signal transduction. Studies have found that during cerebral ischemia and hypoxia, lactate concentration increases significantly, improving the energy supply to the ischemic area. Based on the scientific concept of lactate travelling through the brain, this article focuses on the important role of lactate as an energy source after ischemic stroke and analyzes the relationship between lactate as a signaling molecule and neuroprotection, angiogenesis, and anti-inflammatory effects. The aim of this study is to outline the molecular mechanisms by which lactate exerts its different effects in ischemic stroke. Some references are provided in this study for the research on lactate therapy for ischemic stroke.

Alzheimer's disease (AD) is a progressive condition that causes the degeneration of nerve cells, leading to a decline in cognitive abilities and memory impairment, significantly affecting millions around the globe. The primary pathological feature of AD is the buildup of amyloid-β (Aβ) plaques in the brain, which has become a major target for therapeutic strategies. This thorough review examines the progress made in next-generation therapies that concentrate on monoclonal antibodies (mAbs) aimed at Aβ. We explore how these antibodies function, their effectiveness in clinical settings, and their safety profiles, specifically discussing notable mAbs, such as aducanumab, donanemab, lecanemab, etc. This review also addresses the difficulties related to Aβ- targeted treatments. Furthermore, it examines the advancing field of biomarker development and tailored medicine strategies designed to improve the accuracy of AD treatment. By integrating the latest findings from clinical trials and new research, this review offers an in-depth evaluation of the possibilities and challenges associated with mAbs in modifying the progression of AD. Future considerations regarding combination therapies and novel drug delivery methods are also examined, emphasizing the necessity for ongoing research to achieve significant advancements in managing AD. Through this review, we seek to provide clinicians, researchers, and policymakers with insights into the current landscape and future directions of Aβ-targeted therapies, promoting a deeper understanding of their role in addressing AD.

Neoplastic transformation of B cells of the post-germinative center can lead to oncohematological dyscrasias, which often results in an abnormal production of monoclonal immunoglobulin light chains. The non-physiological production of large amounts of IgG light chains leads to the formation of extracellular deposits called 'aggregomas' and rare conditions such as light chain crystal deposition disease. Kidney manifestations and heavy-chain deposition disease can also occur in plasma cell dyscrasias, emphasizing the role of IgG misfolding and aggregation. This minireview describes molecular mechanisms of IgG light-chain aggregation, as well as the consequences and therapeutic implications of IgG light chain misfolding in these disorders. By elucidating the mechanisms of IgG light chain misfolding and aggregation, researchers can identify specific molecular and cellular pathways. This knowledge opens the door to novel therapeutic targets, offering the potential for interventions that can either prevent the initial misfolding events, promote the proper folding and processing of immunoglobulins, or enhance the clearance of misfolded proteins and aggregates. These protein folding-related issues persist even after the successful elimination of the malignant B cells. Such targeted protein-folding therapies could significantly improve patients' quality of life and contribute to their recovery. Thus, a deep understanding of IgG light chain misfolding and its consequences not only sheds light on the complex biology of oncohematological dyscrasias but also opens the way for innovative treatment strategies that could transform patient care in these conditions, instilling hope and motivation in the healthcare professionals and researchers in this field.

Introduction: Preeclampsia (PE) is an immensely prevalent condition that poses a significant risk to both maternal and fetal health. It is recognized as a primary cause of perinatal morbidity and mortality. Despite extensive research efforts, the precise impact of JDP2 on trophoblast invasion and migration in the context of preeclampsia remains unclear.

Materials and methods: The present study aimed to investigate the differential expression of JDP2 between normal control and preeclampsia placentas through the use of quantitative polymerase chain reaction (qPCR), western blotting, and immunostaining techniques. Furthermore, the effects of JDP2 overexpression and silencing on the migration, invasion, and wound healing capabilities of HTR-8/SVneo cells were evaluated. In addition, this study also examined the impact of JDP2 on epithelial-mesenchymal transition (EMT)-associated biomarkers and the Wnt/β-catenin pathway.

Results: In the present investigation, it was ascertained that Jun dimerization protein 2 (JDP2) exhibited a substantial decrease in expression levels in placentae afflicted with preeclampsia in comparison to those of normal placentae. Impairment in migration and invasion was noted upon JDP2 down-regulation, whereas augmentation of migration and invasion was observed upon JDP2 overexpression in HTR-8/SVneo cells. Subsequently, western blot and immunofluorescence assays were conducted, revealing marked alterations in EMT-associated biomarkers, such as E-cadherin, N-cadherin, and β-catenin, thereby indicating that JDP2 can facilitate cell invasion by modulating the EMT process in HTR-8/SVneo cells. Finally, activation of Wnt/β-catenin signaling was observed as a result of JDP2. After that, IWR-1, a Wnt inhibitor, was used in the recovery study. IWR-1 could inhibit the role of JDP2 in promoting migration and invasion in HTR-8/SVneo cells.

Conclusion: Our findings elucidated the impact of JDP2 on trophoblast invasion and migration in preeclampsia by suppressing the EMT through the Wnt/β-catenin signaling pathway, thereby offering a potential prognostic and therapeutic biomarker for this condition.

Antimicrobial peptides (AMPs) are recognized for their potential application as new generation antibiotics, however, up to date, they have not been widely commercialized as expected. Although current bioinformatics tools can predict antimicrobial activity based on only amino acid sequences with astounding accuracy, peptide selectivity and potency are not foreseeable. This, in turn, creates a bottleneck not only in the discovery and isolation of promising candidates but, most importantly, in the design and development of novel synthetic peptides. In this paper, we discuss the challenges faced when trying to predict peptide selectivity and potency, based on peptide sequence, structure and relevant biophysical properties such as length, net charge and hydrophobicity. Here, pore-forming alpha-helical antimicrobial peptides family isolated from anurans was used as the case study. Our findings revealed no congruent relationship between the predicted peptide properties and reported microbial assay data, such as minimum inhibitory concentrations against microorganisms and hemolysis. In many instances, the peptides with the best physicochemical properties performed poorly against microbial strains. In some cases, the predicted properties were so similar that differences in activity amongst peptides of the same family could not be projected. Our general conclusion is that antimicrobial peptides of interest must be carefully examined since there is no universal strategy for accurately predicting their behavior.

Objective: Proteomic elucidation is an essential step in improving our understanding of the biological properties of proteins in amyotrophic lateral sclerosis (ALS).

Methods: Preliminary proteomic analysis was performed on the spinal cord and brain of SOD1 G93A (TG) and wild-type (WT) mice using isobaric tags for relative and absolute quantitation.

Results: Partial up- and downregulated proteins showing significant differences between TG and WT mice were identified, of which 105 proteins overlapped with differentially expressed proteins in both the spinal cord and brain of progression mice. Bioinformatic analyses using Gene Ontology, a cluster of orthologous groups, and Kyoto Encyclopedia of Genes and Genomes pathway revealed that the significantly up- and downregulated proteins represented multiple biological functions closely related to ALS, with 105 overlapping differentially expressed proteins in the spinal cord and brain at the progression stage of TG mice closely related to 122 pathways. Differentially expressed proteins involved in a set of molecular functions play essential roles in maintaining neural cell survival.

Conclusion: This study provides additional proteomic profiles of TG mice, including potential overlapping proteins in both the spinal cord and brain that participate in pathogenesis, as well as novel insights into the up- and downregulation of proteins involved in the pathogenesis of ALS.

Alzheimer's disease (AD), the most common kind of dementia worldwide, is characterized by elevated levels of the amyloid-β (Aβ) peptide and hyperphosphorylated tau protein in the neurons. The complexity of AD makes the development of treatments infamously challenging. Apolipoprotein E (APOE) genes's ε4 allele is one of the main genetic risk factors for AD. While the APOE gene's ε4 allele considerably increases the chance of developing AD, the ε2 allele is protective compared to the prevalent ε3 variant. It is fiercely discussed how APOE affects the development and course of disease since it has a variety of activities that influence both neuronal and non-neuronal cells. ApoE4 contributes to the formation of tau tangles, deposition of Aβ, neuroinflammation, and other processes. Four decades of research have provided a significant understanding of the structure of APOE and how this may affect the neuropathology and pathogenesis of AD. APOE is a crucial lipid transporter essential for the growth of the central nervous system (CNS), upkeep, and repair. The mechanisms by which APOE contributes to the pathophysiology of AD are still up for discussion, though. Evidence suggests that APOE affects the brain's clearance and deposition of Aβ. Additionally, APOE has Aβ-independent pathways in AD, which has led to the identification of new functions for APOE, including mitochondrial dysfunction. This study summarizes important studies that describe how APOE4 affects well-known AD pathologies, including tau pathology, Aβ, neuroinflammation, and dysfunction of neural networks. This study also envisions some of the therapeutic approaches being used to target APOE4 in the hopes of preventing or treating AD.

Ferritin, as an iron storage protein, has the potential to inhibit ferroptosis by reducing excess intracellular free iron concentrations and lipid reactive oxygen species (ROS). An insufficient amount of ferritin is one of the conditions that can lead to ferroptosis through the Fenton reaction mediated by ferrous iron. Consequently, upregulation of ferritin at the transcriptional or posttranscriptional level may inhibit ferroptosis. In this review, we have discussed the essential role of ferritin in ferroptosis and the regulatory mechanism of ferroptosis in ferritin-deficient individuals. The description of the regulatory factors governing ferritin and its properties in regulating ferroptosis as underlying mechanisms for the pathologies of diseases will allow potential therapeutic approaches to be developed.