- Home
- A-Z Publications
- Protein and Peptide Letters
- Fast Track Listing
Protein and Peptide Letters - Online First
Description text for Online First listing goes here...
-
-
Identifying the Role of Individual Seal IAPP Amino Acids in Inhibiting the Aggregation of Human IAPP
Available online: 10 December 2024More LessIntroductionThe progression of type 2 diabetes in humans appears to be linked to the loss of insulin-producing β-cells. One of the major contributors to β-cell loss is the formation of toxic human IAPP amyloid (hIAPP, Islet Amyloid Polypeptide, amylin) in the pancreas. Inhibiting the formation of toxic hIAPP amyloid could slow, if not prevent altogether, the progression of type 2 diabetes. Many non-human organisms also express amyloidogenic IAPP variants known to kill pancreatic cells and give rise to diabetes-like symptoms. Surprisingly, some of these non-human IAPP variants function as inhibitors of hIAPP aggregation, raising the possibility of developing non-human IAPP peptides into anti-diabetic therapeutic peptides. One such inhibitory IAPP variant is seal IAPP, which has been shown to inhibit hIAPP aggregation. Seal IAPP only differs from hIAPP by three amino acids. In this study, each of the six seal/human IAPP permutations was analyzed to identify the role of each of the three amino acid positions in inhibiting hIAPP aggregation.
AimsThis study aimed to identify the minimal amino acid substitutions to yield a peptide inhibitor of human IAPP aggregation.
ObjectiveThe goal of the study was to determine the minimal amino acid substitutions necessary to convert human IAPP into an amyloid-inhibiting peptide.
MethodsThe formation of toxic hIAPP amyloid was monitored using Thioflavin T binding assays, atomic force microscopy, and MTT cell rescue studies.
ResultsOne seal IAPP variant retained amyloid-inhibition activity, and two variants appeared to be more amyloidogenic and toxic than wild-type human IAPP.
ConclusionThese results suggest that inhibition of hIAPP requires both the H18R and F23L substitutions of hIAPP.
-
-
-
Targeting APE1: Advancements in the Diagnosis and Treatment of Tumors
Authors: Minghui Hu, Yingyu Zhang, Pin Zhang, Kangbo Liu, Mengxin Zhang, Lifeng Li, Zhidan Yu, Xianwei Zhang, Wancun Zhang and Ying XuAvailable online: 06 December 2024More LessWith the emergence of the precision medicine era, targeting specific proteins has emerged as a pivotal breakthrough in tumor diagnosis and treatment. Apurinic/apyrimidinic Endonuclease 1 (APE1) is a multifunctional protein that plays a crucial role in DNA repair and cellular redox regulation. This article comprehensively explores the fundamental mechanisms of APE1 as a multifunctional enzyme in biology, with particular emphasis on its potential significance in disease diagnosis and strategies for tumor treatment. Firstly, this article meticulously analyzes the intricate biological functions of APE1 at a molecular level, establishing a solid theoretical foundation for subsequent research endeavors. In terms of diagnostic applications, the presence of APE1 can be detected in patient serum samples, biopsy tissues, and through cellular in situ testing. The precise detection methods enable changes in APE1 levels to serve as reliable biomarkers for predicting tumor occurrence, progression, and patient prognosis. Moreover, this article focuses on elucidating the potential role of APE1 in tumor treatment by exploring various inhibitors, including nucleic acid-based inhibitors and small molecule drug inhibitors categories, and revealing their unique advantages in disrupting DNA repair function and modulating oxidative-reduction activity. Finally, the article provides an outlook on future research directions for APE1 while acknowledging major technical difficulties and clinical challenges that need to be overcome despite its immense potential as a target for tumor therapy.
-
-
-
Recombinant Production of Ib-AMP4 and Oncorhyncin II Antimicrobial Peptides and Antimicrobial Synergistic Assessment on the Treatment of Staphylococcus aureus Under in vitro Condition
Authors: Majid Safari, Hamid Abtahi, Shima Chehreii and Shohreh FahimiradAvailable online: 26 November 2024More LessBackgroundMethicillin-resistant Staphylococcus aureus (MRSA) is a significant and prevalent pathogen that poses a major challenge in healthcare environments. In light of the growing threat posed by multidrug-resistant organisms like MRSA, there is an urgent need for alternative therapeutic strategies. One promising avenue of research involves the use of antimicrobial peptides (AMPs). These naturally occurring molecules, which are part of the innate immune response in many organisms, have garnered attention for their ability to combat a wide range of pathogens.
ObjectivesThis study aimed to produce recombinant versions of Ib-AMP4 and Oncorhyncin II and to evaluate their combined effects against MRSA (NCTC10442).
MethodsEscherichia coli BL21(DE3] served as the expression host for the synthesized variants of the Ib-AMP4 and Oncorhyncin II genes. The antimicrobial efficacy of these peptides against MRSA S. aureus (NCTC1042] was evaluated using a comprehensive methodology that encompassed the determination of the minimum inhibitory concentration (MIC), the performance of time-kill assays, and the analysis of growth kinetics.
ResultsThe individual antimicrobial activities of Ib-AMP4 and Oncorhyncin II were assessed, revealing minimum inhibitory concentrations (MICs) of 27.75 µg/mL and 40.125 µg/mL against S. aureus (MRSA) (NCTC10442), respectively. The application of a checkerboard assay to evaluate the combination of these antimicrobial peptides (AMPs) demonstrated a synergistic interaction, which was further validated through time-kill and growth kinetic studies. When administered at double the MIC, a significant reduction in the log10 CFU/mL of MRSA (NCTC 10442) was observed, underscoring the synergistic bacteriostatic effect mediated by the fractional inhibitory concentration (FIC) index of the two peptides.
ConclusionAntimicrobial peptides (AMPs) have attracted significant interest owing to the growing intricacy of microbial infections. They constitute a promising category of novel antibiotics that warrant further investigation for the treatment of S. aureus infections and the enhancement of wound healing. Although certain AMPs can operate autonomously, others may necessitate a synergistic approach alongside conventional antibiotics. Studies examining the combined efficacy of Oncorhyncin II and Ib-AMP4 against MRSA in vitro have revealed their effectiveness.
-
-
-
Overexpression of HIF2α Enhances the Angiogenesis-Promoting Effect of hUC-MSC-Derived Extracellular Vesicles by Stimulating miR-146a
Authors: Yihui Chen, Shichai Hong, Zhefeng Wang, Xiang Hong, Gang Chen, Yulong Huang, Yue Lin, Xinsheng Xie, Chenwei Lin and Weifeng LuAvailable online: 25 November 2024More LessObjectiveThis study aimed to explore whether excessive HIF2α can amplify the impact of human Umbilical Cord Mesenchymal Stem Cell-derived Extracellular Vesicles (hUC-MSC-EVs) on endothelial cells.
MethodsIn this study, we created HIF2α-overexpressing hUC-MSC-EVs and compared their pro-angiogenic effects with control EVs on Human Umbilical Vein Endothelial Cells (HUVECs). MTT assay and Edu staining were used to detect the viability and proliferation ability of HUVECs, and Transwell and tube formation assays were used to detect cell migration and tube formation ability. qPCR assay was used to detect the expression of cellular angiogenic markers. Subsequently, miRNAs that might be regulated by HIF2α were predicted by bioinformatics analysis, and qPCR was used to detect the relative expression of miRNAs in HUVECs treated with hUC-MSC-EV, which over-expresses HIF2α. Subsequently, miR-146a inhibitors were used to investigate the role of miR-146a in mediating the pro-angiogenic effect of HIF2α on HUVECs by detecting cell viability, proliferation, migration, tube-forming ability, and expression of angiogenic markers. Finally, AKT/ERK phosphorylation and Spred1 expression were detected using Western blotting.
ResultsOur findings have indicated that overexpression of HIF2α significantly enhances the ability of hUC-MSC-EVs to stimulate proliferation, migration, and tube formation in HUVECs, as demonstrated by MTT/Edu staining, Transwell assay, and tube formation assay results, respectively. Mechanistically, excessive HIF2α has been found to induce the expression of miR-146a in HUVECs and the overexpression of a miR-146a inhibitor to negate the influence of excessive HIF2α on hUC-MSC-EV-induced activity in HUVECs.
ConclusionThe overexpression of HIF2α is an effective strategy for enhancing the pro-angiogenic function of hUC-MSC-EVs.
-
-
-
Leptin/Melanocortin Pathway in Cholelithiasis Patients: A Diagnostic Perspective?
Authors: Tugba Agbektas, Gülşen Güçlü, Ayca Tas, Esma Ozmen, Ömer Topçu, Süleyman Aydin and Yavuz SılıgAvailable online: 22 November 2024More LessBackgroundCholelithiasis is the most prevalent inflammatory condition of the gallbladder. The regulation of biological processes, including energy homeostasis, and control of body weight are key mechanisms that the leptin and melanocortin pathways play a role in.
Cholelithiasis is the most prevalent inflammatory condition of the gallbladder. There are various risk factors for the development of gallstone disease, especially weight gain, and obesity is just one of them. This risk factor can be minimized by maintaining appetite and energy balance. Here, leptin and melanocortin pathways are the key mechanisms in maintaining appetite and energy homeostasis.
ObjectivesThe aim of this study was to investigate the relationship between the levels of LEP, LEPR, TrkB, BDNF, POMC, and MC4R proteins in patients with Cholelithiasis.
This study aims to determine the relationship between LEP, LEPR, TrkB, BDNF, POMC, and MC4P protein levels, which play a role in maintaining appetite and energy homeostasis, and cholelithiasis.
MethodsThis study examined 44 patients diagnosed with Cholelithiasis and 44 healthy control subjects who had not previously been diagnosed with any form of Cholelithiasis. The levels of leptin (LEP), Leptin Binds To Leptin Receptors (LEPR), Tropomyosin Receptor Kinase B (TrkB), Brain-Derived Neurotrophic Factor (BDNF), Pro-OpioMelanoCortin (POMC), and Melanocortin-4 Receptors (MC4R) molecules were analyzed using the Enzyme-Linked Immunosorbent Assay (ELISA) method. The results were analyzed using the SPSS Software (Version 22.0) program and GraphPad Prism 8.0.1 software.
ResultsThe study found a statistically significant decrease (p < 0.05) in MC4R, TrkB, BDNF, and POMC protein levels in Cholelithiasis patients compared to the control group. There was no statistically significant difference in LEP and LEPR concentration values between the two groups (p=0.247, p=0.674).
ConclusionThe proteins MC4R, TrkB, BDNF, and POMC, which are involved in the leptin and melanocortin pathways may play a significant role in Cholelithiasis disease. However, more detailed research on the relevant proteins is needed. Nevertheless, this research will guide new studies.
-
-
-
Exploring the Regulatory Interaction of Differentially Expressed Proteins in Cleft Palate Induced by Retinoic Acid
Authors: Liyun Chen, Aiwei Ma, Lewen Jiang, Jufeng Fan, Wenshi Jiang, Mengjing Xu, Xujue Bai, Jianda Zhou, Wancong Zhang and Shijie TangAvailable online: 25 October 2024More LessObjectiveThis study aimed to identify novel proteins involved in retinoic acid (RA)-induced embryonic cleft palate development.
MethodThe palate tissues of the control and RA-treated E14.5 were dissected and subjected to iTRAQ-based proteomic analysis.
ResultsDifferential expression analysis identified 196 significantly upregulated and 149 downregulated considerably proteins in RA-induced palate tissues. Comprehensive Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed the significant involvement of cytoplasmic translation, ribosome biogenesis, glycolysis/gluconeogenesis, and glutathione metabolism pathways in cleft palate pathogenesis triggered by RA. In particular, ribosome-related pathways were highly enriched, while glycolysis was disrupted. Protein-protein interaction analysis, facilitated by the STRING database, revealed a tightly interconnected network of differentially expressed proteins. Further analysis using the cytoHubba plugin in Cytoscape identified ten hub proteins, including Eif4a1, Gapdh, Eno1, Imp3, Rps20, Rps27a, Eef2, Hsp90ab1, Rpl19, and Rps16, indicating their potential roles in RA-induced cleft palate development, and thus positioning them as potential biomarkers for cleft palate.
ConclusionThese findings provide valuable insights into the proteomic changes associated with RA-induced cleft palate and shed light on key pathways and proteins that can contribute significantly to the pathogenesis of this congenital condition.
-