Current protein & peptide science最新文献

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.

Background: Glioblastoma is a common primary malignant intracranial tumor in adults associated with high disability and mortality. Despite the use of traditional surgical methods, postoperative radiotherapy, and targeted therapies, the median survival for glioma patients remains disappointingly brief. As a result, there is an urgent need to explore new targets and develop novel targeted drugs to potentially improve patient survival. Notably, CLIC1 expression is upregulated in tumors and correlated to tumor aggressiveness, metastasis, and poor prognosis. Nonetheless, its potential role in gliomas remains largely unclear.

Objective: This study aimed to investigate the bioinformatics characteristics and clinicopathological features of CLIC1, including WHO classification and OS.

Methods: Immunohistochemistry and western blot analysis were carried out to detect the expression of CLIC1 in glioma tissues. Moreover, CCK8, plate clone formation assay, and EdU proliferation assay were carried out for cell proliferation ability. Transwell and scratch assay were performed for cell invasion and migration. Western blotting was also conducted to verify the relationship between CLIC1 and EMT and ERK1/2 signaling pathway. The effect of the knockdown of CLIC1 on tumor growth capacity was assessed in an intracranial xenograft model.

Results: CLIC1 was found to be associated with poor prognosis in glioma patients, and in vivo experiments demonstrated that CLIC1 promoted GBM cell proliferation, invasion, and migration. In addition, CLIC1 positively regulated ERK1/2 signaling to promote the EMT process in GBM cells. In vitro experiments showed that CLIC1 could affect intracranial tumor progression in mice.

Conclusion: In summary, these findings expand our knowledge of CLIC1, confirming its oncogenic role and laying the groundwork for future development of pharmacological agents targeting this gene.

Purpose: The purpose of this study was to design and synthesize the ug46 peptide, incorporate its fibrils into composite materials, and evaluate its structural and antimicrobial properties. Another objective was to utilize spectroscopy and molecular simulation, enhanced by Machine Vision methods, to monitor the aggregation process of the ug46 peptide and assess its potential as a scaffold for an antimicrobial peptide.

Method: The structural analysis of the ug46 peptide reveals its dynamic conformational changes. Initially, the peptide exhibits a disordered structure with minimal α-helix content, but as incubation progresses, it aggregates into fibrils rich in β-sheets. This transformation was validated by CD and ThT assays, which showed decreased molar ellipticity and an increase in ThT fluorescence.

Results: Laser-induced fluorescence and molecular dynamics simulations further revealed the transition from a compact native state to extended "worm-like" filament structures, influenced by peptide concentration and temperature. TEM and AFM confirmed these changes, showing the evolution of protofibrils into mature fibrils with characteristic twists. When incorporated into chitosan- bioglass composites, these fibrils significantly enhanced antimicrobial activity against pathogens such as Staphylococcus aureus and Pseudomonas aeruginosa.

Conclusion: Overall, ug46 peptide fibrils show promise as a multifunctional scaffold with structural and antimicrobial benefits in composite biomaterials.

Introduction: Secreted Frizzled-Related Protein 2 (SFRP2) is considered to be the most potent modulator of the Wnt signaling. This pathway is involved in the pathogenesis of Polycystic Ovary Syndrome (PCOS). This research aimed to compare the levels of SFRP2 in PCOS [infertile and Recurrent Pregnancy Loss (RPL) patients] with the control group and determine the correlation of SFRP2 with inflammation and insulin resistance.

Methods: This case-control study was conducted on 108 POCS patients (53 infertile patients and 55 women with RPL) and 54 healthy controls. The levels of biochemical factors along with SFRP2, adiponectin, Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH), free testosterone, and insulin, high-sensitivity C-Reactive Protein (hs-CRP) were measured following the manufacturer's instructions.

Results: Both infertile and RPL groups presented notably higher levels of SFRP2 (49.32 ± 17.72 ng/ml and 55.89 ± 17.36 ng/ml, respectively) compared to the control group (30.21 ± 10.12 ng/ml, P<0.001 for both groups). In PCOS patients, a positive correlation was observed between SFRP2 and body mass index (BMI) (r = 0.42, P < 0.001), insulin (r = 0.19, P = 0.04), fasting blood glucose (FBG) (r = 0.24, P = 0.01), Homeostatic Model Assessment for Insulin Resistance (HOMA- IR) (r = 0.21, P = 0.03), triglyceride (r = 0.25, P = 0.009), and hs-CRP (r = 0.21, P = 0.02). Furthermore, SFRP2 increased the risk of RPL (OR [95% CI] = 1.15 [1.10 -1.20], P < 0.001) and infertility (OR [95% CI] = 1.12 [1.07 -1.17], P < 0.001) in comparison with the controls.

Conclusion: Our findings suggested that SFRP2 may have a potential involvement in the development of PCOS and might be a promising target for diagnosis, but additional research is required to confirm this.

Background: Colorectal cancer (CRC) is one of the most common malignancies worldwide, and despite advances in treatment, there remains a critical need for novel therapeutic approaches. Recently, anti-microbial peptides (AMPs) have gained attention for their potential use in cancer therapy due to their selective cytotoxicity towards cancer cells.

Objective: This study aims to evaluate the anti-cancer potential of two computationally engineered anti-microbial peptides (EAMPs) in SW620, SW480, and HCT116 colon cancer cells and the normal colon epithelial cell line CCD 841, focusing on their effects on cell proliferation, apoptosis, and DNA damage.

Method: Cell proliferation and survival were measured using the CellTiter-Glo Luminescence and clonogenic assays. DNA damage was assessed through the Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Flow cytometry was used to examine cell apoptosis, cell cycle distribution, and mitochondrial membrane potential in SW620 cells.

Results: EAMPs inhibited CRC cell proliferation in a dose-dependent manner, with minimal toxicity observed in normal colon epithelial cells. In SW620 cells, EAMPs induced DNA damage, resulting in cell cycle arrest at the S/G2 phase, apoptosis, and a reduction in mitochondrial membrane potential. The proliferation results were confirmed in SW480 and HCT116 CRC cell lines.

Conclusion: Our findings revealed that EAMPs exhibited significant anti-cancer activity against CRC cells in vitro while sparing normal epithelial cells. These results suggest that EAMPs may offer a potential therapeutic approach for colorectal cancer and warrant further investigation.

A special kind of posttranslational process known as proteolytic cleavage controls the half-lives and functions of several extracellular and intracellular proteins. The metalloproteinase ADAM10 has attracted attention because it cleaves a growing amount of protein substrates close to the extracellular membrane leaflet. The process known as "ectodomain shedding" controls the turnover of certain transmembrane proteins that are essential for receptor signaling and cell adhesion. It may trigger nuclear transport, intramembrane proteolysis, and cytoplasmic domain signaling. Additional human illnesses linked to ADAM10 include cancer, immune system malfunction, and neurodegeneration. The difficulty in targeting proteases for medicinal reasons stems from the many substrates that these enzymes, particularly ADAM10, have. It is usually necessary to precisely identify the therapeutic beneficial window of use since blocking or accelerating a particular protease activity is linked with undesirable side effects. More knowledge of the regulatory pathways governing ADAM10 expression, subcellular localization, and activity will probably lead to the identification of viable therapeutic targets, enabling more targeted and precise manipulation of the enzyme's proteolytic activity.

The misfolding and aggregation of amyloid proteins are closely associated with a range of neurodegenerative diseases. Liquid-liquid phase separation (LLPS) can initiate the aggregation of proteins, indicating that LLPS may serve as an alternative pathway for the pathological aggregation of amyloid proteins. The co-occurrence of two or more amyloid pathologies has been observed in extensive pathophysiological studies and is linked to faster disease progression. The co- LLPS (also known as co-condensation) and co-aggregation of different disease-related proteins have been proposed as a potential molecular mechanism for combined neuropathology. Here, we reviewed the current state of knowledge regarding the co-aggregation and co-condensation of various amyloid proteins, including Aβ, tau, α-synuclein, TDP-43, FUS, and hnRNPA/B protein family, C9orf72 dipeptide repeats and prion protein. We briefly introduced the epidemiological correlation among different neurodegenerative diseases and specifically presented recent experimental findings about co-aggregation and co-condensation of two different amyloid proteins. Additionally, we discussed computational studies focusing on the molecular interactions between amyloid proteins to offer mechanistic insights into the co-LLPS and co-aggregation processes. This review provides an overview of the synergistic interactions between different disease-related proteins, which is helpful for understanding the mechanisms of combined neuropathology and developing targeted therapeutic strategies.

Background: Cathepsin D is a lysosomal enzyme that plays a critical role in the process of protein catabolism. In marine organisms, research has primarily concentrated on the identification of the enzyme. However, in crustaceans and molluscs, it is known to have digestive functions, as it is the sole enzyme responsible for protein degradation at extremely acidic pH in the hepatopancreas. In the Japanese clam (Ruditapes philippinarum), cathepsin D was purified and partially characterised by the hepatopancreas.

Methods: To evaluate changes in secondary structure, circular dichroism (CD) was employed under a range of 5-70°C and pH of 1-7.5. Following dissection, the enzyme was purified from the hepatopancreas by ultrafiltration and affinity chromatography. SDS-PAGE was used to verify the sample purity, and gel filtration was used to determine the molecular weight.. CD spectra were obtained at a concentration of 0.125 mg/mL, expressed as mean ellipticity per residue.

Results: The purified cathepsin D demonstrated a specific activity of 5,553 ± 220 U/mg and a molecular weight of 36.5 kDa. The enzyme demonstrated optimal activity within a temperature range of 45-50°C and a pH range of 3-3.5. CD analyses demonstrated alterations in the secondary structure at elevated temperatures and pH fluctuations, which were correlated with a reduction in enzyme activity.

Conclusion: cathepsin D from R. philippinarum exhibited high thermostability up to 50°C and activity at pH 2-4. Its stability and characteristics are comparable to those of other species, which opens avenues in biotechnology for protein hydrolysis and peptide production.

In recent years, novel therapeutic approaches have revolutionized the landscape of medicine, offering promising avenues for the cure of various diseases. The novel approaches explore advancements in gene therapy in pharmaceuticals, immunotherapy, RNA-based therapeutics, cell-based therapies, and targeted tumor therapies. Gene therapy has emerged as a groundbreaking approach, leveraging genetic material to cure or prevent diseases by targeting defective genes. In pharmaceuticals, gene therapy holds immense potential for addressing genetic disorders, offering a personalized approach to medicine. Immunotherapy, on the other hand, harnesses the body's immune system to combat diseases, including tumors, by enhancing immune responses or directly targeting malignant cells. RNA-based therapeutics have gained prominence due to their ability to modulate gene expression, offering targeted and precise interventions for a wide range of diseases. Cell-based therapies involve the transplantation or manipulation of cells to restore or enhance their function, offering innovative solutions for diseases such as neurodegenerative disorders and cardiovascular diseases. Furthermore, targeted tumor therapies have revolutionized tumor cure by specifically targeting molecular alterations driving tumor growth and minimizing damage to healthy cells. Overall, these novel therapeutic approaches represent a paradigm shift in medicine, offering tailored and precise interventions with the potential to significantly improve patient outcomes and quality of life.