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- Volume 31, Issue 9, 2024
Protein and Peptide Letters - Volume 31, Issue 9, 2024
Volume 31, Issue 9, 2024
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Investigation of the Expression and Regulation of SCG5 in the Context of the Chromogranin-Secretogranin Family in Malignant Tumors
Authors: Weisong Zhang, Rui Wang, Zhongquan Yi, Rongqi Guo, Yangyang Li, Yanhan Xu, Xia Li and Jianxiang SongThe SCG5 gene has been demonstrated to play an essential role in the development and progression of a range of malignant neoplasms. The regulation of SCG5 expression involves multiple biological pathways. According to relevant studies, SCG5 is differentially expressed in different cancers, and its up- or down-regulation may even affect tumour growth, invasion, and migration, which caught our attention. Therefore, we summarise the regulatory roles played by the SCG5 gene in a variety of cancers and the biological regulatory mechanisms associated with its possible promotion or inhibition of tumour biological behavior, to further explore the potential of SCG5 as a new tumour marker and hopefully provide theoretical guidance for subsequent disease research and treatment.
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Neuropeptide Network of Polycystic Ovary Syndrome – A Review
BackgroundPolycystic Ovary Syndrome (PCOS), the ubiquitous reproductive disorder, has been documented as highly prevalent (6-9%) in India. 10% of women globally are predicted to have the disease. The highly mutable endocrinopathy, with differential clinical criteria for each diagnosis of PCOS, can mask the severity of the syndrome by influencing the incidence and occurrence of PCOS.
Area CoveredWhen there is a solid theoretical hypothesis between the neuroendocrine origin and ovarian origin of PCOS, recent evidence supports the neuroendocrine derivation of the pathology. It is considered of neuroendocrine basis – as it controls the ovarian axis and acts as a delicate target because it possesses receptors for various gonadal hormones, neurotransmitters & neuropeptides. Can these neuroendocrine alterations, variations in central brain circuits, and neuropeptide dysregulation be the tie that would link the pathophysiology of the disorder, the occurrence of all the 1˚ and 2˚ symptoms like polycystic ovaries, hyperandrogenism, obesity, insulin resistance, etc., in PCOS?
ConclusionThis review anticipates providing a comprehensive overview of how neuropeptides such as Kisspeptin, Neurokinin B, Dynorphin A, β-Endorphin, Nesfatin, Neuropeptide Y, Phoenixin, Leptin, Ghrelin, Orexin, and Neudesin influence PCOS, the understanding of which may help to establish potential drug candidates against precise targets in these central circuits.
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Revealing the Molecular Signatures of miR-185-5p on Breast Cancer Cells Using Proteomic Analysis
Authors: Vildan Torun, Elif Değerli and Demet Cansaran-DumanBackgroundBreast cancer is a heterogeneous type of disease in which genetic and environmental factors play a crucial role. There are several types of treatment for breast cancer (BC) patients. However, the biggest problem in the treatment of breast cancer is the resistance that occurs during the treatment with chemotherapeutic agents. Usnic acid, a secondary metabolite of lichen, has been identified as a drug candidate molecule in cancer treatment. The determination of miRNA target proteins is essential for the understanding of molecular mechanisms of miRNA-related tumorigenesis.
ObjectivesWe determined that mir-185-5p has therapeutic potential at the miRNA level by applying usnic acid to BT-474 breast cancer cells in a previous study. Herein, we aimed to investigate the molecular mechanisms of miR-185-5p on BT-474 breast cancer cells using a proteomics approach. We explored the changes in the protein expression level of BT-474 breast cancer cells in response to the up-regulation of miR-185-5p after applying usnic acid as a novel candidate anti-cancer drug molecule.
MethodsWe performed quantitative proteome analysis based on an LC-MS/MS assay, which was validated by western blotting. The differentially expressed proteins were analyzed using the latest data available in bioinformatics tools. The up-regulated expression of YWHAE, Cathepsin D, and the down-regulated levels of PAK-1 were demonstrated by western blot assay.
ResultsAccording to the results, 86 proteins showing >2-fold change were identified as differentially expressed between breast cancer and normal breast epithelial cells. The apoptosis pathway was the main clade containing most of the proteins regulated by miR-185-5p. The results indicate that miR-185-5p modulates apoptosis signaling pathways in BT-474 breast cancer cells. Breast cancer inhibition due to increased expression of YWHAE, Cathepsin D, and decreased expression of PAK-1 is likely to be mediated by inducing miR-185-5p mediated apoptosis.
ConclusionIn this study, the identification of miR-185-5p protein targets demonstrated the potential for the development of targeted therapy and the development of miRNA-based therapeutics and presented it as a biomarker for breast cancer diagnosis, prognosis, and treatment response. In this regard, proteome analyses provided an understanding of the molecular mechanism underlying the effect of miR-185-5p on breast cancer.
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Immunogenicity and Neutralization Potential of Recombinant Chimeric Protein Comprising the Catalytic Region of Gp63 of Leishmania and LTB against Leishmania donovani
Authors: Anuja Krishnan, Gunjan Malik and Lalit C. GargAimTo study the inhibition potential of antibody against a recombinant chimera comprising of the catalytic epitope of gp63 of Leishmania donovani and B subunit of heat-labile enterotoxin (LTB) in the functional activity of L. donovani.
BackgroundVisceral leishmaniasis, caused by the protozoan parasite Leishmania donovani, is a major health problem and causes mortality in tropical regions. Protozoan proteases play a crucial role in the pathogenesis of the disease and in establishing infection by countering the host's innate immune responses, namely complement-mediated lysis and phagocytosis. A surface-bound metalloprotease (gp63) has been reported to be a major virulence factor resulting in the evasion of complement-mediated lysis, cleaving host extracellular and intracellular substrates, resulting in intra-phagolysosomal survival.
MethodsThe epitope corresponding to the catalytic motif of gp63 of Leishmania donovani was fused with the B subunit of heat-labile enterotoxin, which is known to be immunogenic. The chimera was cloned to a prokaryotic expression vector and purified using Ni NTA affinity chromatography. Antibodies were generated against the purified fusion protein and analyzed for its ability to bind to the gp63 catalytic motif peptide by ELISA. The effect of fusion protein antibody on the functional activity of gp63 was evaluated by assessing the effect of purified IgGs on the protease activity and complement-mediated lysis of L. donovani promastigotes in vitro.
ResultsThe present study reports that a recombinant chimera of the catalytic epitope of gp63 and B subunit of heat-labile enterotoxin (LTB) of E. coli, a potent adjuvant of humoral response can mount significant immune response towards the catalytic epitope. ELISA and Western blot analysis showed that the anti-fusion protein antiserum could recognize the native gp63. Also, it significantly inhibited the protease activity of promastigotes and subsequently increased complement-mediated lysis of the promastigotes in vitro.
ConclusionIt could be concluded that the hybrid protein containing catalytic motif L. donovani gp63 protein and carrier protein (LTB) could elicit antibodies that could neutralise the functional activity of gp63 and thus could be a potential candidate for subunit leishmaniasis vaccine.
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Association between Higher Expression of Vav1 in Hepatocellular Carcinoma and Unfavourable Clinicopathological Features and Prognosis
Authors: Weikang Ye, Jin Wang, Jie Zheng, Ming Jiang, Yinong Zhou and Zhixiang WuObjectiveThe aim was to investigate the potential relationship between Vav1 protein and prognosis in patients with hepatocellular carcinoma (HCC).
MethodsSamples were collected from 96 patients with HCC. For each patient, cancerous tissue and adjacent non-cancerous tissue were obtained. The Vav1 expression levels in these tissues were determined using immunohistochemistry. Chi-square and Fisher's exact tests were used to analyse the associations between Vav1 expression and clinicopathological characteristics. Kaplan–Meier analysis was used to assess the relationship between Vav1 expression and 5-year overall survival (OS).
ResultsThe expression level of Vav1 protein in primary tumour samples (64.46%; 59/96) was higher (33.33%; 32/96; P<0.001). Moreover, the high expression rate of Vav1 was correlated with tumour differentiation, TNM stage, and tumour recurrence (P<0.05). Univariate and multivariate Cox analysis further demonstrated that tumour differentiation, TNM stage, vascular invasion, tumour recurrence and Vav1 expression were independent prognostic factors for 5-year OS. Notably, follow-up analysis determined that patients with HCC with higher Vav1 expression levels have lower survival rates (P<0.05).
ConclusionVav1 may serve as a promising molecular prognostic biomarker for patients diagnosed with HCC.
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Investigating In silico and In vitro Therapeutic Potential of Diosmetin as the Anti-Parkinson Agent
Authors: Krishna Kumar Varshney, Jeetendra Kumar Gupta and Rajnish SrivastavaAimThis study aimed to investigate how diosmetin interacts with seven target receptors associated with oxidative stress (OS) and validate its antioxidant properties for the potential management of Parkinson’s disease (PD).
BackgroundIn PD, the degeneration of dopaminergic cells is strongly influenced by OS. This stressor is intricately connected to various mechanisms involved in neurodegeneration, such as mitochondrial dysfunction, neuroinflammation, and excitotoxicity induced by nitric oxide.
ObjectiveThe aim of this research was to establish a molecular connection between diosmetin and OS-associated target receptors was the goal, and it investigated how this interaction can lessen PD.
MethodsSeven molecular targets - Adenosine A2A (AA2A), Peroxisome Proliferator-Activated Receptor Gamma (PPARγ), Protein Kinase AKT1, Nucleolar Receptor NURR1, Liver - X Receptor Beta (LXRβ), Monoamine Oxidase - B (MAO-B) and Tropomyosin receptor kinase B (TrkB) were obtained from RCSB. Molecular docking software was employed to determine molecular interactions, while antioxidant activity was assessed through in vitro assays against various free radicals.
ResultsDiosmetin exhibited interactions with all seven target receptors at their binding sites. Notably, it showed superior interaction with AA2A and NURR1 compared to native ligands, with binding energies of -7.55, and -6.34 kcal/mol, respectively. Additionally, significant interactions were observed with PPARγ, AKT1, LXRβ, MAO-B, and TrkB with binding energies of -8.34, -5.42, -7.66, -8.82, -8.45 kcal/mol, respectively. Diosmetin also demonstrated antioxidant activity against various free radicals, particularly against hypochlorous acid (HOCl) and nitric oxide (NO) free radicals.
ConclusionDiosmetin possibly acts on several target receptors linked to the pathophysiology of PD, demonstrating promise as an OS inhibitor and scavenger.
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A Conserved Tryptophan (Trp10) at the Hydrophobic Core Modulates the Stability and Inhibitory Activity of Potato I Type Inhibitors
Authors: Xiaodong Cui, Jiahui Shen, Jiajie Wang, Chen Li, Fang Li and Jiao LiBackgroundDifferent inhibitor families have their own conserved three-dimensional structures, but how these structures determine whether a protein can become an inhibitor is still unknown. The buckwheat trypsin inhibitor (BTI) pertains to the Potato I type inhibitor family, which is a simple and essential bio-molecule that serves as a model for the investigation of protease-inhibitor interaction.
ObjectiveTo study the effects of mutations at Trp10 and Ile25 in the hydrophobic cavity (scaffold) of rBTI on its inhibitory activity and stability.
MethodsSite-directed mutagenesis and molecular modeling were performed using the sequence of BTI. The hydrogen bonds formed by all amino acids and conformational differences of Trp53 were analyzed in the tertiary structures of rBTI and mutants.
ResultsMutant rBTI-W10A almost completely lost its inhibitory activity (retaining 10%), while rBTI-I25A retained about 50% of its inhibitory activity. Both rBTI-W10A and rBTI-I25A could be degraded by trypsin. The hydrogen bond analysis results showed that mutating Trp10 or Ile25 weakened the specific cohesion interactions in the hydrophobic core of rBTI, disrupting the tight hydrogen bond network in the cavity. This further led to difficulty in maintaining the binding loop conformation, ultimately causing the Trp53 to undergo conformational changes. It was also difficult for residues in the mutants to form hydrogen bonds with amino acids in bovine trypsin; thus, the mutants could not stably bind to trypsin.
ConclusionOur findings suggest that the hydrophobic core is also an important factor in the maintenance of inhibitory activity and stability of rBTI.
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Volumes & issues
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Volume 31 (2024)
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Volume 30 (2023)
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Volume 29 (2022)
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Volume 28 (2021)
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Volume 27 (2020)
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Volume 26 (2019)
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Volume 25 (2018)
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Volume 24 (2017)
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Volume 23 (2016)
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Volume 22 (2015)
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Volume 21 (2014)
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Volume 20 (2013)
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Volume 19 (2012)
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Volume 18 (2011)
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Volume 17 (2010)
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Volume 16 (2009)
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Volume 15 (2008)
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Volume 14 (2007)
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Volume 13 (2006)
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Volume 12 (2005)
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Volume 11 (2004)
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Volume 10 (2003)
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Volume 9 (2002)
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Volume 8 (2001)