Current protein & peptide science最新文献

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.

Methods: 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.

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.

Introduction: The Q108P pathological variant of the mitochondrial Coiled-Coil-Helix-- Coiled-Coil-Helix Domain-Containing Protein 10 (CHCHD10) has been implicated in amyotrophic lateral sclerosis (ALS). Both the wild-type and CHCHD10^Q108P proteins exhibit intrinsically disordered regions, posing challenges for structural studies with conventional experimental tools.

Methods: This study presents the foundational characterization of the structural features of CHCHD10^Q108P and compares them with those of the wild-type counterpart. We conducted multiple run molecular dynamics simulations and bioinformatics analyses.

Results: Our findings reveal distinct differences in structural properties, free energy surfaces, and the outputs of principal component analysis between these two proteins. These results contribute significantly to the comprehension of CHCHD10 and its Q108P variant in terms of pathology, biochemistry, and structural biology.

Conclusion: The reported structural properties hold promise for informing the development of more effective treatments for ALS.

Introduction: Diabetic nephropathy is characterized by elevated oxidative stress and chronic inflammation in the kidneys. A class of proteins called sirtuins is well-known to be important for a number of cellular functions, such as metabolism, stress tolerance, and ageing. Among them, SIRT1 is associated with the progression of diabetic nephropathy, a dangerous kidney-related consequence of diabetes mellitus. Thus, this study aims to examine the function and pathways of sirtuin that are responsible for the progression of this disease.

Methods: Publications considered from the standard databases like Pubmed-Medline, Google Scholar, and Scopus using standard keywords, "Sirtuin," Signalling pathway", and "Diabetic Nephropathy" well described the actual knowledge on the scientific literature indicating patient susceptibility to kidney disease that is influenced by sirtuin-1 gene variants.

Results: The research results imply that sirtuins offer enormous promise as cutting-edge therapeutic targets for kidney disease prevention and management. Renal fibrosis, metabolic disorders, renal impairment, and a possible regulation mechanism all probably entail blocking inflammation through various signalling pathways.

Conclusion: A comprehensive understanding of the fundamental pathophysiological pathways targeting sirtuin is essential as a diagnostic tool. For the treatment of diabetic nephropathy, researchers are developing therapeutic techniques to target biological roles and functions of different types of sirtuin, processes, and signalling pathways.

The diagnosis of intestinal injury remains a challenge as it is rare in occurrence and transpires in multiple traumatized patients. The deferred finding of injury of intestines upsurges multiple risks such as septicemia, numerous organ failures as well as mortality. In this review, we corroborate with the goals of proposing surrogate biomarkers that consent to the measurement of the permeability of intestines more effortlessly. The expression of intestinal fatty acid binding protein (I-FABP) is exclusive in the intestine and has been reported to release extracellularly upon damage caused to tissues. This work focuses on evaluating the legitimacy of I-FABP as an initial biomarker to distinguish abdominal damage predominantly from an injury to the intestine.

Introduction: The rising prevalence of Mycobacterium tuberculosis (M.tb) strains resistant to aminoglycosides (amikacin and kanamycin) challenges effective TB control and treatment. Understanding the mechanisms behind this resistance is crucial since aminoglycosides are a mainstay of TB therapy.

Aim: The study aimed to analyze the cell wall proteins overexpressed in aminoglycosides-resistant isolates of Mycobacterium tuberculosis using proteomics approaches.

Methods: We used two-dimensional electrophoresis and mass spectrometry to compare the cell wall proteomes of aminoglycosides-resistant and susceptible clinical isolates. The overexpressed protein spots were excised and identified using liquid chromatography-mass spectrometry (LC/MS). The identified proteins were subsequently analyzed for molecular docking, pupylation site identification, and STRING analysis.

Results: We found a total of nine significantly upregulated proteins in aminoglycosides-resistant isolates. Three of these proteins were the same (isoform), resulting in the identification of seven unique proteins. Specifically, Rv3841 and Rv1308 belonged to intermediary metabolism and respiration; Rv2115c to the cell wall and cell processes; Rv2501c, Rv2247 and Rv0295c to lipid metabolism; and Rv2416c to virulence, detoxification/adaptation. Notably, variations in these proteins support cell wall integrity, aiding mycobacteria's establishment and proliferation. Molecular docking study revealed that both drugs bind strongly to the proteins' active site regions. Additionally, the GPS-PUP algorithm successfully identified possible pupylation sites within these proteins, except Rv0295c. Based on interactome analysis using the STRING 12.0 database, we have identified potential interactive partners suggesting their role in aminoglycosides resistance.

Conclusion: Overexpressed proteins not only act to counteract or regulate drug effects but also have a role in protein dynamics that allow for resistance. Some of these identified proteins may serve as innovative drug targets and biomarkers for the early detection of drug-specific resistance in M.tb. Further research is needed to elucidate the mechanisms by which these potential protein targets contribute to resistance in AK and KM M.tb isolates.

Baicalein (BN) is an active ingredient naturally present in Chinese herbs, such as Scutellaria baicalein, Coptis chinensis, and Dendrobium officinale. It has a variety of pharmacological activities, including antioxidant, anti-inflammatory and antibacterial effects. Therefore, Baicalein (BN) is widely used in the field of medicine and is considered a potential natural medicine. Osteoporosis (OP) is a bone metabolic disease characterized by decreased bone mineral density and bone structure destruction, which is mainly caused by decreased bone formation and increased bone resorption. With the continuous development of molecular biology, the signaling pathways and gene targets of bone metabolism are also expanding. Recent studies have shown that baicalein may affect the function of osteoblasts, osteoclasts, and bone marrow mesenchymal stem cells through MAPK/ERK and MAPKs/NF-κB signaling pathways, so as to have a therapeutic effect on OP. However, the specific mechanism of baicalein in the treatment of OP is still unclear. This article reviews the literature, analyzes and summarizes the mechanism of action of baicalein, and discusses its potential in the prevention and treatment of OP, so as to provide a basis for the clinical application of baicalein.

Introduction: The PICK1 PDZ domain has been identified as a potential drug target for neurological disorders. After many years of effort, a few inhibitors, such as TAT-C5 and mPD5, have been discovered experimentally to bind to the PDZ domain with a relatively high binding affinity. With the rapid growth of computational research, there is an urgent need for more efficient computational methods to design viable ligands that target proteins.

Method: Recently, a newly developed program called AfDesign (part of ColabDesign) at https:// github.com/sokrypton/ColabDesign), an open-source software built on AlphaFold, has been suggested to be capable of generating ligands that bind to targeted proteins, thus potentially facilitating the ligand development process. To evaluate the performance of this program, we explored its ability to target the PICK1 PDZ domain, given our current understanding of it. We found that the designated length of the ligand and the number of recycles play vital roles in generating ligands with optimal properties.

Results: Utilizing AfDesign with a sequence length of 5 for the ligand produced the highest comparable ligands to that of prior identified ligands. Moreover, these designed ligands displayed significantly lower binding energy compared to manually created sequences.

Conclusion: This work demonstrated that AfDesign can potentially be a powerful tool to facilitate the exploration of the ligand space for the purpose of targeting PDZ domains.

The phenomenon of Liquid-Liquid Phase Separation (LLPS) serves as a vital mechanism for the spatial organization of biomolecules, significantly influencing the elementary processes within the cellular milieu. Intrinsically disordered proteins, or proteins endowed with intrinsically disordered regions, are pivotal in driving this biophysical process, thereby dictating the formation of non-membranous cellular compartments. Compelling evidence has linked aberrations in LLPS to the pathogenesis of various neurodegenerative diseases, underscored by the disordered proteins' proclivity to form pathological aggregates. This study meticulously evaluates the arsenal of contemporary experimental and computational methodologies dedicated to the examination of intrinsically disordered proteins within the context of LLPS. Through a discerning discourse on the capabilities and constraints of these investigative techniques, we unravel the intricate contributions of these ubiquitous proteins to LLPS and neurodegeneration. Moreover, we project a future trajectory for the field, contemplating on innovative research tools and their potential to elucidate the underlying mechanisms of LLPS, with the ultimate goal of fostering new therapeutic avenues for combating neurodegenerative disorders.