Protein and Peptide Letters最新文献

{"title":"Unveiling the Potential Role of Hesperetin and Emodin as a Combination Therapy to Inhibit the Pancreatic Cancer Progression against the C-Met Gene.","authors":"Rangaraj Kaviyaprabha, Thandaserry Vasudevan Miji, Puthupparambil Shaji Sreelakshmi, Sridhar Muthusami, Palanisamy Arulselvan, Muruganantham Bharathi","doi":"10.2174/0109298665363165250225100109","DOIUrl":"https://doi.org/10.2174/0109298665363165250225100109","url":null,"abstract":"<p><strong>Background: </strong>Pancreatic adenocarcinoma (PAAD) is one of the most prevalent cancers, and it has high death rates. Only 10% of PAAD patients can survive until 5 years. Hence, the improvement of survival rate of the patients should be improved.</p><p><strong>Aim: </strong>The present study used a computational approach to identify novel biomarkers and potentially effective small drug-like molecules in PAAD.</p><p><strong>Objective: </strong>The objective of this study was to identify the Differentially Expressed Genes (DEGs) and survival rate affecting genes (SDEGs) to single out the specific gene responsible for pancreatic cancer and predict the efficacy of interactions with hesperetin and emodin. Further, another objective was to validate the predicted efficacies using an MTT assay.</p><p><strong>Methods: </strong>The GEPIA2 database was used to analyze the TCGA-PAAD dataset and identify DEGs and SDEGs. Venn identified the commonly scattered genes between the DEGs and SDEGs. Network Analyst v3.0, CytoScape v3.10.1, and cytoHubba were used for PPI network construction and hub genes identification was described as target proteins. The PDB and PubChem were utilized to obtain the PDB structure of the target proteins and 13 phytocompounds in SDF format. Molecular docking studies were carried out and visualized by utilizing Autodock vina and Discovery Studio Visualizer v19.1.0.1828. The cytotoxicity was measured in the MiaPaCa-2 cell line after being treated with hesperetin and emodin.</p><p><strong>Results: </strong>A total of 9219 Differentially Expressed Genes (DEGs) from the TCGA-PAAD dataset were identified. Among them, 8740 and 479 genes were up and down-regulated with the statistical significance of P ≤ 0.05, respectively. Likely, 500 most survival rate affecting genes (SDEGs) in PAAD patients with a statistical significance of P ≤ 0.05 were identified. The common 137 genes were identified between these obtained DEGs and SDEGs. The survival heat map was delineated for the predicted 137 common genes. Ninety-six genes were identified as the most hazardous genes (highlighted in red). After that, the network was constructed by using protein-protein interaction (PPI) for the most hazardous 96 genes. From the constructed PPI network, the highly interacted top 10 genes were identified. The survival analysis was carried out to identify the most hazardous genes and revealed that all the identified genes significantly reduced the survival rate of the patients affected by PAAD. From that, high survival affecting 5 genes, such as CDK1, CENPE, NCAPG, KIF20A, and c-MET, were selected for further analysis. The molecular docking studies were carried out for the identified top 5 genes, with the 13 phytocompounds reviewed previously for anti-cancer activity. The molecular docking analysis revealed that the hesperetin (binding affinity (BA) = -8.0 kcal/mol; Root mean square deviation (RMSD) = 2.012 Å) and emodin (BA = -8.6 kcal/mol; RMSD = 1.605 ","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Plant-derived Cyclotides in Immunomodulation and their Therapeutic Potential.","authors":"Reema Mishra, Preeti Agarwal, Anshita Sharma, Meenal Mittal, Pooja Gulati, Aparajita Mohanty","doi":"10.2174/0109298665364479250214101422","DOIUrl":"https://doi.org/10.2174/0109298665364479250214101422","url":null,"abstract":"<p><p>The incidences of immune-related disorders have drastically increased in recent years across the world population. Treatment and management of these diseases, especially autoimmune disorders, are complex and challenging. Available synthetic drugs are not completely effective and also pose serious side effects for the patients. Cyclotides are a class of plant-derived cyclic peptides (28-37 amino acids) with three conserved disulfide linkages establishing a cyclic cystine knot (CCK) motif that makes them very stable biomolecules. Their inherent stability, bioavailability and membrane-penetrating capabilities render them attractive potential pharmacological agents. Studies have demonstrated that cyclotides can either enhance or suppress immune responses, making them versatile candidates for treating various immune-related disorders. Of more than 1000 cyclotides discovered to date, only up to 15 native cyclotides (e.g. kalata B1, pase and caripe cyclotides) have been screened to demonstrate their immunomodulatory activity. Of special significance is the chemically synthesised lysine mutant of kalata B1 viz. [T20K], where preclinical studies have shown promise in the treatment of the autoimmune disorder, multiple sclerosis. In vivo studies in mice models have demonstrated that daily administration of 1mg/day of [T20K] led to a significant decrease in the level of cytokine secretion, lesser demyelination (<1%) and very low inflammatory index (<0.5), in the immunized mice. Moreover, when compared with other immunosuppressive drugs (azathioprine, prednisolone, and cyclosporine A) there was a notable drop in mortality and morbidity in mice administered with [T20K]. The cyclotides, kalata B1 and MCoTI-I have also been used as scaffolds to graft bioactive peptides with immunomodulatory activity. Subsequent in vitro and in vivo studies of these grafted cyclotides have demonstrated their therapeutic ability. Keeping in view the therapeutic potential of cyclotides as immunomodulatory peptides, the present review discusses its current research scenario and implications for the future in tackling immune-related disorders.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diminazene Aceturate (DIZE) Ameliorates Hypertension and Induces Anxiolytic- and Antidepressant-like Effects in TGR(mRen2)27","authors":"Laura A Costa, Flávio A G Mourão, Natalia Alenina, Michael Bader, Maria Jose Campagnole-Santos, Lucas M Kangussu","doi":"10.2174/0109298665357730250213050214","DOIUrl":"10.2174/0109298665357730250213050214","url":null,"abstract":"<p><strong>Introduction: </strong>Diminazene aceturate (DIZE) was described as an angiotensin-converting enzyme 2 (ACE2) activator. ACE2/Angiotensin-(1-7)/Mas receptor axis presents protective actions on cardiovascular diseases and plays an important modulatory role in the neurobiology of mood and anxiety disorders.</p><p><strong>Objectives: </strong>To evaluate the effects of chronic intracerebroventricular (ICV) treatment with DIZE on blood pressure, anxiety- and depression-like behaviors in hypertensive transgenic (mRen2)27 rats (TGR).</p><p><strong>Methods: </strong>Male TGR and Sprague-Dawley rats (10-12 weeks old) were subjected to chronic ICV infusion of DIZE (1.0 μg/h for 7 days). Blood pressure and heart rate were measured by tail plethysmography and anxiety- and depression-like behaviors were evaluated through elevated plus maze, marble burying and forced swim tests, respectively.</p><p><strong>Results: </strong>Treatment with DIZE induced a significant reduction in mean arterial pressure in both TGR and SD rats. A decrease in heart rate was only observed in the hypertensive animals. Additionally, treatment with DIZE attenuated the anxiety- and depression-like behaviors that were observed in TGR.</p><p><strong>Conclusion: </strong>DIZE has central anti-hypertensive, anxiolytic, and anti-depressive effects.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative In Silico and In Vitro Studies of Novel Zinc/Tin Metal Coordinates Bearing BRCA-1 Mimetics on Wtp53 and Mtp53 Proteins.","authors":"Preeya Negi, Akey Krishna Swaroop, Anuj Kumar Singh, R Saranya, M Esakkimuthukumar, P Vasanth Raj, N Jawahar, S Jubie","doi":"10.2174/0109298665361116250121103146","DOIUrl":"https://doi.org/10.2174/0109298665361116250121103146","url":null,"abstract":"<p><strong>Purpose: </strong>This study compares the activity of BRCA-1 mimetics on WTp53 (wild-type p53 protein) and MTp53 (mutated-type p53 protein) proteins, examining the impact of TP53 mutations in breast cancer. p53 activators can be a new insight and synthesis of effective compounds for the treatment of cancer. The project contributes to the growing body of research on p53 activators and provides new insights into the design and synthesis of effective compounds for the treatment of cancer.</p><p><strong>Methods: </strong>Molecular docking predicted binding affinity values for WTp53 and MTp53. The MMGBSA of top compounds was run to get binding-free energies. The MD simulations were calculated, and six metal coordinates were synthesized. In vitro MTT-assays were performed with WTp53 (MCF-7) and R273H-MTp53 (MDA-MB-468) cell lines, comparing results with known p53 activator PRIMA-1 (p53-reactivation and induction of massive apoptosis-1).</p><p><strong>Results: </strong>The p53 activators established a three-featured (2RA, 1HBA) pharmacophore. The designed compounds had better Glide gscore compared to p53 activators PRIMA-1, PRIMA-1- MET (methylated PRIMA-1), and Tamoxifen with p53 protein (WTp53, R175H and R273H MTp53). The MM-GBSA results of top compounds showed binding free energies with R175HMTp53 (-22.24 to -75.45 kcal/mol), R273H-MTp53 (-22.8 to -36.36 kcal/mol), and WTp53 (-26.45 to -50.3 kcal/mol) compared to the p53 activator. The MD simulation of TSCO5/3KMD-MT in 100 ns indicated a stable complex when compared to TSCO5/3KMD-WT. The six metal coordinates (TSCO5-Zn, TSCO6-Zn, TSCO6-Sn, TSCO13-Zn, TSCO13-Sn, TSCO9-Sn) were synthesised. Based on in vitro results, IC50 for TSCO5-Zn (WTp53: 0.089μM, MTp53: 0.074μM) and TSCO5- Sn (WTp53: 0.092μM, MTp53: 0.073μM) have shown significant cytotoxicity.</p><p><strong>Conclusion: </strong>As compared to PRIMA-1, the designed compound TSCO5 metal coordinates have shown good in silico and in vitro activity on mutated p53 cell lines and are more potent than the p53 activator PRIMA-1.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143410138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-584-5p Regulates MSMO1 to Modulate the AKT/PI3K Pathway and Inhibit Breast Cancer Progression.","authors":"Xin Li, Jie Liu, Lili He, Mi Tian, Yingying Xu, Bing Peng","doi":"10.2174/0109298665339026250114070523","DOIUrl":"https://doi.org/10.2174/0109298665339026250114070523","url":null,"abstract":"<p><strong>Introduction: </strong>Endogenous microRNAs (miRNAs) are critical regulators of tumor progression, making their role in breast cancer an important area of investigation.</p><p><strong>Method: </strong>This study examined the regulation of MSMO1 by miR-584-5p in breast cancer cells. Using bioinformatics and Western blotting, we confirmed MSMO1 expression in breast cancer cells and evaluated its effects on cell migration, invasion, and the AKT signaling pathway. In vivo experiments further supported these findings. The interaction between miR-584-5p and MSMO1 was validated through luciferase reporter assays, while functional studies highlighted the impact of miR-584-5p on cancer progression.</p><p><strong>Result: </strong>Our findings revealed that MSMO1 is upregulated in breast cancer, enhancing cell migration and invasion. Silencing MSMO1 diminished AKT pathway activity, and luciferase assays confirmed MSMO1 as a direct target of miR-584-5p.</p><p><strong>Conclusion: </strong>Overexpression of miR-584-5p suppressed migration and invasion of breast cancer cells. In summary, miR-584-5p is likely to modulate MSMO1 and subsequently regulate the AKT/ PI3K pathway, presenting a promising therapeutic target for breast cancer treatment.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Review on the Potential Role of Humanin Peptide and its Analogs in the Regulation of Autophagy Pathways for Therapeutic Application in Metabolic Disorders.","authors":"Hira Moin, Rizwan Ashraf, Batool Butt, Imtiaz Mustafa, Mamoona Shafiq, Sayed Ali Raza Shah","doi":"10.2174/0109298665363711250112050930","DOIUrl":"https://doi.org/10.2174/0109298665363711250112050930","url":null,"abstract":"<p><p>Autophagy is a self-eating cellular process in which the cell breaks down worn-out organelles, damaged/defective proteins, and toxins. Impaired autophagy is a significant factor in the development of various metabolic disorders, along with oxidative stress, inflammation, mitochondrial and endoplasmic reticulum dysfunction. These disorders pose a significant health and economic burden on the global human population, owing to their steadily rising prevalence. Therefore, modulating the expression of proteins involved in the autophagy-related pathways can be a promising avenue for curbing the development and progression of these disorders. Humanin (HN) is a 24-amino acid mitochondrial-derived peptide. It possesses anti-oxidant, anti-inflammatory, and pro-apoptotic properties. The analogs of HN can be generated by replacing specific amino acids in the polypeptide chain, thereby functionally modifying the peptide. Among these, humanin- glycine (HNG) is the most widely studied analog in both in vivo and in vitro disease models. It is far more potent than HN, with a potency that is 1000 times greater. To the best of our knowledge, this review is the first to discuss and examine the available evidence regarding the potential involvement of HN or its analogs in regulating autophagy pathways. The review primarily highlights that HN is an autophagy inducer, which can promote cell survival in the presence of metabolic and oxidative stress, particularly the HNG analog. Future research is imperative to comprehensively evaluate the effects of HN and its analogs on autophagy. Further investigations are needed to correlate its levels with various autophagic markers in different metabolic diseases, offering the potential for groundbreaking discoveries in understanding disease mechanisms and developing novel therapeutic strategies.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inconsistent Protein Stability Despite Pre-HECT Domain Helix: Unveiling Variability in HECT Ligases.","authors":"Çağdaş Dağ, Cansu Deniz Tozkoparan Ceylan, Cemre Sare Cansız","doi":"10.2174/0109298665362863250114075840","DOIUrl":"https://doi.org/10.2174/0109298665362863250114075840","url":null,"abstract":"<p><strong>Introduction: </strong>Ubiquitin and ubiquitin-like systems play crucial roles across a wide range of organisms, from simple to complex. Among the three enzyme-mediated post-translational modification (PTM) steps, the ligation step is the most critical. HERC5, a member of the HECT ligase family, is one of the three enzymes involved in the ISGylation system. However, the precise start points and lengths of the HECT domains in HECT ligases are still under debate.</p><p><strong>Method: </strong>Some studies suggest the inclusion of an additional N-terminal alpha helix region within the HECT domain. To investigate the structural biology of the HECT domain of HERC5, we produced and purified various lengths of the HERC5 HECT domain using different fusion proteins. This approach allowed us to explore the role of the N-terminal alpha helix in the stability of the HECT domain. Our experiments successfully produced and purified HERC5 HECT domains of different lengths with various fusion proteins.</p><p><strong>Result: </strong>The findings demonstrated that the N-terminal alpha-helix does not enhance the stability of the HECT domain. These results challenge the notion that the N-terminal alpha-helix should be generally included in the HECT domain across all HECT ligases.</p><p><strong>Conclusion: </strong>The inclusion of this region within the HECT domain may not be appropriate for generalization, as it does not contribute to stability, contrary to some previous suggestions.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Cancer Bioactive Peptide Induces Apoptosis in Gastric Cancer Cells through TP53 Signaling Cascade.","authors":"Qimuge Suyila, Xian Li, Xiulan Su","doi":"10.2174/0109298665350654250111144722","DOIUrl":"https://doi.org/10.2174/0109298665350654250111144722","url":null,"abstract":"<p><strong>Introduction: </strong>Gastric cancer has emerged as one of the major diseases threatening human health. Our previous studies indicated that the anti-cancer bioactive peptide (ACBP) inhibits the initiation and progression of gastric cancer through apoptosis and cell cycle arrest, yet the mechanisms remain unclear. To elucidate the relationships between the effects of ACBP and the levels of cell differentiation, as well as the functional mechanisms of ACBP, we conducted a study using three human gastric cancer cell lines: NCI-N87, MGC-803, and another unspecified line.</p><p><strong>Method: </strong>We investigated the impact of ACBP on the survival and morphology of these cancer cell lines, examined apoptosis and cell cycle progression, and detected the expression of TP53, TP63, and TP73 in cancer cells, as well as the expression of Bax, PUMA, and Mcl-1 in a xenograft mouse model. ACBP inhibited the proliferation of all three cancer cell lines in a dose-dependent manner, similar to the positive control and 5-fluorouracil (5-FU). The effect of ACBP correlated with the degree of differentiation of the cancer cells; the lower the differentiation degree, the stronger the inhibitory effect.</p><p><strong>Result: </strong>After ACBP treatment, the expression of TP53, TP63, and TP73 increased in all cell lines. In the xenograft mouse model, ACBP inhibited the growth of MGC-803 cells in vivo. The apoptotic- related genes Bax and PUMA were upregulated, while Mcl-1 was downregulated. ACBP inhibited tumor cell growth by inducing apoptosis through the TP53 signaling cascade, upregulating TP53, TP63, and TP73 and their downstream apoptosis-promoting genes Bax and PUMA while downregulating the anti-apoptotic gene Mcl-1.</p><p><strong>Conclusion: </strong>Notably, after ACBP treatment, Mcl-1 expression was significantly reduced in the tumor tissue of the xenograft model, indicating that ACBP induced apoptosis through the TP53 signaling cascade. This project provides a scientific basis for exploring the antitumor mechanism of ACBP in gastric cancer therapy.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"iRGD Tumor Penetrating Peptide-Modified NK Cells Exhibit Enhanced Tumor Immune Infiltration Ability and Anti-Tumor Efficacy.","authors":"Ge Song, Xueyong Qi, Yi Zhao","doi":"10.2174/0109298665348639250115113650","DOIUrl":"https://doi.org/10.2174/0109298665348639250115113650","url":null,"abstract":"<p><strong>Background: </strong>Natural killer (NK) cells, as part of the group I innate lymphocytes (ILCs) are essential for tumor immune surveillance. NK cells can recognize and eliminate target cells without the need for prior sensitization or restriction of major histocompatibility complexes (MHCs) and antigens. However, the limited infiltration of metastatic NK cells poses significant challenges for advancing adoptive cell immunotherapy for solid tumors.</p><p><strong>Objective: </strong>This study aimed to explore the potential of using tumor penetrating peptide (TPP) iRGD to promote the delivery of activated NK cells to deeper layers of tumor tissue.</p><p><strong>Methods: </strong>Flow cytometry was performed to evaluate the activation, inhibition, and expression of other receptors involved in cytotoxicity. High-pressure liquid chromatography (HPLC) and mass spectrometry were used to detect the purity of iRGD. 1,2-distearoyl-sn-glycero-3- phosphoethanolamine-poly(ethylene glycol)-iRGD (DSPE-PEG-iRGD) was synthesized. Surface modification of cells was performed using DSPE-PEG-iRGD. Multicellular tumor spheroids (MCTSs) were established to evaluate permeability. In addition, in order to better simulate the physiological characteristics of solid tumors in vivo, we generated 3D spheroids from HGC27 gastric cancer cell line and BXPC-3 pancreatic cancer cell line to study the anti-tumor effect of NK cells with combination iRGD in vitro. The mouse models of gastric cancer and pancreatic cancer were used. In addition, the synergistic anti-tumor effects were evaluated in vivo based on the tumor volume and body weight of mice.</p><p><strong>Results: </strong>Initially, we treated NK cells with interleukin-2 (IL-2), resulting in significant activation as indicated by upregulation of CD56. On the 15th day, the proliferation of CD3-/56+cell population in NK cell culture containing IL-2 significantly increased, and the NK cell amplification factor was greater than 300. In addition, NK cells exhibited increased cytotoxicity towards cancer cell lines. When the ratio of effect to target was 10:1, the killing rate of NK cells against BXPC-3 was 83.1%. iRGD modification enabled NK cells to penetrate MCTSs, resulting in cytotoxicity against target HGC27 and BXPC-3 cells. In addition, NK cells modified with iRGD significantly reduced tumor growth in the xenotransplantation model of gastric cancer and pancreatic cancer mice model.</p><p><strong>Conclusion: </strong>In summary, our results indicated that NK cells exhibited higher efficacy and lifespan against cancer cell lines in vitro. Furthermore, the integration of iRGD into NK cells led to improved infiltration and targeted elimination of MCTSs. Moreover, the application of iRGDmodified NK cells has shown significant anti-tumor efficacy against solid tumors in vivo. This joint strategy may significantly improve the efficacy of NK cell immunotherapy in treating various solid tumors.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143415058","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Interactions of the Antimicrobial Peptide Tritrpticin with Mixed Nanoaggregates: A Fluorescence Spectroscopy Study.","authors":"Kaio César Antunes Rocha, Maria Carolina Oliveira de Arruda Brasil, Eduardo Maffud Cilli, Luiz Carlos Salay","doi":"10.2174/0109298665359223241226091327","DOIUrl":"https://doi.org/10.2174/0109298665359223241226091327","url":null,"abstract":"<p><strong>Introduction: </strong>Tritrpticin (TRP3) is a peptide belonging to the cathelicidin family and has a broad spectrum of antimicrobial activity. However, this class of biomolecules can be easily degraded in the body, making it necessary to use an efficient transport system. The ability to form stable nanostructures from the interaction of glycyrrhizin saponin with the pluronic polymer F127 was demonstrated, forming mixed biopolymeric micelles, highly promising as drug carriers.</p><p><strong>Objective: </strong>The present work sought to understand the physicochemical interaction of the antimicrobial peptide TRP3 with the mixed polymeric micelle made from pluronic F127 and the saponin glycyrrhizin.</p><p><strong>Methods: </strong>The interaction of tritrpticin with mixed nanostructured micelles was evaluated through fluorescence spectroscopy and fluorescence quenching with acrylamide. The experiments were performed at room temperature (25 ± 1°C), adopting an excitation wavelength set to 280 nm and emission between 300 and 500 nm, with a slit of 5 nm.</p><p><strong>Results: </strong>The interaction of the cationic peptide tritrpticin with the mixed biopolymeric micelles was observed through the blue shift of the fluorescence emission to shorter wavelengths, proving the change of tryptophan to a more hydrophobic environment. Through the fluorescence suppression technique, it was possible to indicate the location of the peptide in the mixed micelles, proving tritrpticin to be partially inserted inside them.</p><p><strong>Conclusion: </strong>It was concluded that tritrpticin interacted with mixed nanostructured micelles, forming a promising system for biotechnological applications.</p>","PeriodicalId":20736,"journal":{"name":"Protein and Peptide Letters","volume":" ","pages":""},"PeriodicalIF":1.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}