Bioscience Reports

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ISSN / EISSN : 0144-8463 / 1573-4935
Published by: Portland Press Ltd. (10.1042)
Total articles ≅ 5,649
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Published: 26 September 2022
Dynamin is one of the major proteins involved in endocytosis. First identified 50 years ago in a genetic screen in Drosophila melanogaster, it has become a central player in many forms of endocytosis, such as clathrin-mediated endocytosis or synaptic vesicle endocytosis, as well as other important cellular processes such as actin remodelling. Decades of work using biochemical and structural studies, cell-free assays, live cell imaging, acute inhibition and genetic studies have led to important insights on its mode of action. Dynamin is a remarkable mechano-GTPase which can do a lot to membranes on its own but which is, in cells, at the centre of a vast protein and lipid network and cannot work in isolation. These results have been synthetized in several important reviews and viewpoints [1–3]. In this review, I will summarize the main features of dynamin structure and function and its central role in membrane remodelling events, and give an update on the latest results.
, Dominique J Bicout, Rémi Baroso, Marie-Hélène Paclet, Christian Drouet
Published: 26 September 2022
Human kallikrein-kinin system (KKS) is a proteolytic cascade with two serine-protease zymogen couples (Factor XII and prekallikrein (PK) and their activated forms, FXIIa, PKa respectively) releasing bradykinin by cleavage of native high molecular weight kininogen (nHK) into cleaved HK. For KKS investigation in human plasma, this cascade is usually triggered on ice eventually by mixing with purified proteins. It has been established that purified FXIIa, PK and nHK required a fixed order and timing for mixing protein on ice to ensure reproducibility of testing, we investigated the activation kinetics of both enzymes. The activation process of this in vitro minimal reconstitution of KKS was studied by progress curve analysis, in condition of high enzyme/substrate ratio and by using on natural rather than peptide substrates. FXIIa and PKa were found 5-times less active on ice than at 37°C: kcat=0.133±0.034s-1 and 0.0119±0.0027s-1, KM=672±150nM and 115±24nM, respectively. The progress curve analysis of our in vitro KKS reconstitutions differed from a Michaelis-Menten mathematical simulation by a faster initial rate and a slower late rate. These two features were also observed ex vivo by using dextran-sulphate activated plasma and could reinforce the hypothesis of a maximal local effect (bradykinin release) and a minimal systemic consequence (PK preservation) in KKS activation process.Analyzing the complete curve of cold KKS activation would provide valuable information for ex vivo investigation of KKS in samples from patients presenting with hereditary angioedema and other inflammatory conditions.
, Keely E.A Oldham, Jack McGarvie, Emma J Walker
Published: 23 September 2022
Antibiotics are the cornerstone of modern medicine and agriculture, and rising antibiotic resistance is one the biggest threats to global health and food security. Identifying new and different druggable targets for the development of new antibiotics, is absolutely crucial to overcome resistance. Adjuvant strategies that either enhance the activity of existing antibiotics or improve clearance by the host immune system provide another mechanism to combat antibiotic resistance. Targeting a combination of essential and non-essential enzymes that play key roles in bacterial metabolism, is a promising strategy to develop new antimicrobials and adjuvants, respectively. The enzymatic synthesis of L-cysteine is one such strategy. Cysteine plays a key role in proteins and is crucial for the synthesis of many biomolecules important for defense against the host immune system. Cysteine synthesis is a two-step process, catalyzed by two enzymes. Serine acetyltransferase (CysE) catalyzes the first step to synthesize the pathway intermediate O-acetylserine, and O-acetylserine sulfhydrylase (CysK/CysM) catalyzes the second step using sulfide or thiosulfate to produce cysteine. Disruption of the cysteine biosynthesis pathway results in dysregulated sulfur metabolism, altering the redox state of the cell leading to decreased fitness, enhanced susceptibility to oxidative stress and increased sensitivity to antibiotics. In this review we summarize the structure and mechanism of characterized CysE and CysK/CysM enzymes from a variety of bacterial pathogens, and the evidence that supports targeting these enzymes for the development of new antimicrobials or antibiotic adjuvants. In addition, we explore and compare compounds identified thus far that target these enzymes.
Pritika Mala, , Romila Gopalan, Desta Gedefaw, Katy Soapi
Published: 23 September 2022
Medicinal plants (MPs) are natural sources of active compounds with potential therapeutic benefits in alleviating various illnesses for decades. Fijian people also are using these MPs for the management/prevention of T2DM and associated complications. However, till date, none of these Fijian MP’s antidiabetic potential have been explored/or evaluated. Here, we investigated the antidiabetic potential of Fijian MPs scientifically. Phytochemicals such as polyphenols were detected to inhibit the activity of α-amylase and α-glucosidase; the two key carbohydrate enzymes linked to T2DM. Therefore, in this study, TPC, α-amylase and α-glucosidase inhibitory activity of five Fijian MPs were collected & evaluated.The ME extracts of BO (0.102 ± 0.009 mM CE) and DC (0.098 ± 0.09 mM CE) showed a higher TPC compared to the control. The ME extracts of MF and MR inhibited α-glucosidase significantly in compare to acarbose as evidenced from the IC50 values (IC50 of MF = 1.58 ± 0.03 ng/µL; IC50 of MR = 1.87 ± 0.43 ng/µL and IC50 of acarbose = 3.34 ± 0.15 ng/µL). Moreover, DM extracts of MR (IC50 = 1.31 ± 0.29 ng/µL) also showed significantly higher α-glucosidase inhibitory activity. In contrary, MR (IC50 = 16.18 ± 0.16 ng/µL) and CL (IC50 = 9.21 ± 0.51 ng/µL) also showed significant α-amylase inhibitory activity in ME and DM extracts, respectively. These, results suggest that Fijian MPs could be a potential source of natural inhibitors of enzymes involved in carbohydrate digestion and thus may possibly be used in managing T2DM.
Prafull Salvi, Vishal Varshney,
Published: 23 September 2022
Seed vigor and longevity are important agronomic attributes, as they are essentially associated with crop yield and thus the global economy. Seed longevity is a measure of seed viability and the most essential property in gene bank management since it affects regeneration of seed recycling. Reduced seed life or storability is a serious issue in seed storage since germplasm conservation and agricultural enhancement initiatives rely on it. The irreversible and ongoing process of seed deterioration comprises a complex gene regulatory network and altered metabolism that results in membrane damage, DNA integrity loss, mitochondrial dysregulation, protein damage, and disrupted antioxidative machinery. Carbohydrates and/or sugars, primarily RFOs, have emerged as feasible components for boosting or increasing seed vigor and longevity in recent years. RFOs are known to perform diverse functions in plants, including abiotic and biotic stress tolerance, besides being involved in regulating seed germination, desiccation tolerance, vigor, and longevity. We emphasised and analysed the potential impact of RFOs on seed vigor and longevity in this review. Here, we comprehensively reviewed the molecular mechanisms involved in seed longevity, RFO metabolism, and how RFO content is critical and linked with seed vigor and longevity. Further molecular basis, biotechnological approaches, and CRISPR/Cas applications have been discussed briefly for the improvement of seed attributes and ultimately crop production. Likewise, we suggest advancements, challenges, and future possibilities in this area.
Yanpeng Ding, Jiayu Fang, Mengge Chen, Yulian Xu, Nuomin Liu, Shang Fang, Wenbin Xiang, Rui Chen, Chaoyan Wu,
Published: 23 September 2022
The MT1 family was previously shown to be involved in metal ion homeostasis, DNA damage, oxidative stress, and carcinogenesis. Our team’s previous study showed that MT1X is most closely associated with ccRCC. However, its role in ccRCC remains unclear. This study aimed to demonstrate MT1X’s prognostic value, potential biologic function, impact on the immune system, and influence on cell growth, the cell cycle, apoptosis, and migration in the setting of ccRCC. The relationship between clinical pathologic features and MT1X was analyzed using bioinformatics. We knocked down MT1X in the ccRCC cell line 786O with si-MT1X to verify the results of the bioinformatic analysis at the cytological level. Apoptosis assay, cell cycle assay, wound-healing assay, colony formation assay, and RT-qPCR were performed. MT1X is correlated with the stage (T and M) and grade and is able to be an independent prognostic factor for ccRCC. The TISIDB database analysis showed a significant correlation between MT1X and tumor-infiltrating lymphocytes. MT1X was also positively related to immunomodulators such as TGFB1 and CXCR4. We also found that MT1X knockdown inhibits cell growth, induces apoptosis, arrests cells in the S cell cycle, and inhibits the wound healing proportion in ccRCC. GSEA and q-PCR analysis found that downregulation of MT1X reduced the accumulation of hypoxia-associated factors. Bioinformatic analysis associated increased MT1X expression with a worse prognosis. Laboratory experiments confirmed bioinformatic findings. MT1X was also found to be an independent prognostic biomarker for ccRCC and is involved in immune system regulation.
Jiantong Sun, Danlian Wu, Guangjuan Xu, Fang Chen, Xinyuan Ding, Linjun Xie, Zhangfeng Yu,
Published: 22 September 2022
The addition of olanzapine to fluoxetine produces an antidepressant effect on fluoxetine nonresponders. Promoting hippocampal neurogenesis is associated with the successful treatment of depression. The present study aimed to investigate the interaction of olanzapine and fluoxetine in regulating neurogenesis. We found that fluoxetine alone does not affect cell proliferation and inhibits the neuronal differentiation of cultured neural stem cells (NSCs), but promotes NSCs proliferation and exerts no effect on neuronal fate when NSCs are co-cultured with neurons. In addition, fluoxetine alone also does not alter the neuronal fate of newborn hippocampal cells in vivo. Although fluoxetine treatment elicits different results, our data consistently show that olanzapine alone does not affect the proliferation and neuronal differentiation of NSCs. The combination of olanzapine and fluoxetine has no profound effect on NSCs proliferation compared with fluoxetine alone, but olanzapine add-on treatment produces a greater number and percentage of differentiated neurons from NSCs. Further investigations are needed to explore the underlying mechanisms of the increased neurogenesis caused by the combination of olanzapine with fluoxetine.
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