Biochimie最新文献_第3页

Dietary monoterpenoids and human health: Unlocking the potential for therapeutic use. 膳食单萜与人类健康：挖掘治疗潜力。

Biochimie Pub Date : 2024-09-10 DOI: 10.1016/j.biochi.2024.09.002

Barbora Vyhlídalová, Karolína Ondrová, Iveta Zůvalová

引用次数: 0

Cysteine cathepsins: From diagnosis to targeted therapy of cancer. 半胱氨酸胰蛋白酶：从诊断到癌症靶向治疗。

Biochimie Pub Date : 2024-09-06 DOI: 10.1016/j.biochi.2024.09.001

Ana Ercegovič Rot, Matija Hrovatin, Bor Bokalj, Ernestina Lavrih, Boris Turk

引用次数: 0

New transaminase from Odontosyllis undecimdonta the first potential enzyme of the luciferin biosynthesis pathway. 来自 Odontosyllis undecimdonta 的新转氨酶是荧光素生物合成途径的第一个潜在酶。

Biochimie Pub Date : 2024-08-31 DOI: 10.1016/j.biochi.2024.08.012

Daria A Dmitrieva, Olga A Belozerova, Alexey V Mishin, Ilia V Yampolsky, Alexey A Kotlobay

引用次数: 0

Unlocking the potential of histone modification in regulating bone metabolism. 挖掘组蛋白修饰在调节骨代谢中的潜力。

Biochimie Pub Date : 2024-08-21 DOI: 10.1016/j.biochi.2024.08.004

Jiayuan Zhang, Hanghang Liu, Yao Liu, En Luo, Shibo Liu

引用次数: 0

Luminescence-based complementation assay to assess target engagement and cell permeability of glycolate oxidase (HAO1) inhibitors. 基于荧光的互补测定法，用于评估乙醇酸氧化酶（HAO1）抑制剂的靶参与性和细胞渗透性。

Biochimie Pub Date : 2024-08-14 DOI: 10.1016/j.biochi.2024.08.011

Sabrina R Mackinnon, Tryfon Zarganes-Tzitzikas, Cassandra J Adams, Paul E Brennan, Wyatt W Yue

{"title":"Luminescence-based complementation assay to assess target engagement and cell permeability of glycolate oxidase (HAO1) inhibitors.","authors":"Sabrina R Mackinnon, Tryfon Zarganes-Tzitzikas, Cassandra J Adams, Paul E Brennan, Wyatt W Yue","doi":"10.1016/j.biochi.2024.08.011","DOIUrl":"10.1016/j.biochi.2024.08.011","url":null,"abstract":"Glycolate oxidase (HAO1) catalyses the synthesis of glyoxylate, a common metabolic intermediate that causes renal failure if accumulated. HAO1 inhibition is an emerging treatment for primary hyperoxaluria, a rare disorder of glyoxylate metabolism. Here we report the first cell-based measurement of inhibitor uptake and engagement with HAO1, by adapting the cellular thermal shift assay (CETSA) based on Nano luciferase complementation and luminescence readout. By profiling the interaction between HAO1 and four well-characterised inhibitors in intact and lysed HEK293T cells, we showed that our CETSA method differentiates between low-permeability/high-engagement and high-permeability/low-engagement ligands and is able to rank HAO1 inhibitors in line with both recombinant protein methods and previously reported indirect cellular assays. Our methodology addresses the unmet need for a robust, sensitive, and scalable cellular assay to guide HAO1 inhibitor development and, in broader terms, can be rapidly adapted for other targets to simultaneously monitor compound affinity and cellular permeability.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141997067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Enzymatic activity of HIV-1 protease defines migration of tumor cells in vitro and enhances their metastatic activity in vivo. hiv-1 蛋白酶的酶活性决定了肿瘤细胞在体外的迁移并增强其在体内的转移活性。

Biochimie Pub Date : 2024-08-14 DOI: 10.1016/j.biochi.2024.08.009

M Isaguliants, A Zhitkevich, S Petkov, T Gorodnicheva, D Mezale, I Fridrihsone, Y Kuzmenko, D Kostyushev, A Kostyusheva, I Gordeychuk, E Bayurova

{"title":"Enzymatic activity of HIV-1 protease defines migration of tumor cells in vitro and enhances their metastatic activity in vivo.","authors":"M Isaguliants, A Zhitkevich, S Petkov, T Gorodnicheva, D Mezale, I Fridrihsone, Y Kuzmenko, D Kostyushev, A Kostyusheva, I Gordeychuk, E Bayurova","doi":"10.1016/j.biochi.2024.08.009","DOIUrl":"10.1016/j.biochi.2024.08.009","url":null,"abstract":"Overexpression of aspartic proteases, as cathepsin D, is an independent marker of poor prognosis in breast cancer, correlated with the incidence of clinical metastasis. We aimed to find if HIV-1 aspartic protease (PR) can play a similar role. Murine adenocarcinoma 4T1luc2 cells were transduced with lentivirus encoding inactivated drug-resistant PR, generating subclones PR20.1 and PR20.2. Subclones were assessed for production of reactive oxygen species (ROS), expression of epithelial-mesenchymal transition (EMT) factors, and in vitro migratory activity in the presence or absence of antioxidant N-acetyl cysteine and protease inhibitors. Tumorigenic activity was evaluated by implanting cells into BALB/c mice and following tumor growth by calipering and bioluminescence imaging in vivo, and metastases, by organ imaging ex vivo. Both subclones expressed PR mRNA, and PR20.2, also the protein detected by Western blotting. PR did not induce production of ROS, and had no direct effect on cell migration rate, however, treatment with inhibitors of drug-resistant PR suppressed the migratory activity of both subclones. Furthermore, expression of N-cadherin and Vimentin in PR20.2 cells and their migration were enhanced by antioxidant treatment. Sensitivity of in vitro migration to protease inhibitors and to antioxidant, known to restore PR activity, related the effects to the enzymatic activity of PR. In vivo, PR20.2 cells demonstrated higher tumorigenic and metastatic activity than PR20.1 or parental cells. Thus, HIV-1 protease expressed in breast cancer cells determines their migration in vitro and metastatic activity in vivo. This effect may aggravate clinical course of cancers in people living with HIV-1.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Novel chimeric peptides based on endomorphins and ghrelin receptor antagonist produced supraspinal antinociceptive effects with reduced acute tolerance in mice. 基于内啡肽和胃泌素受体拮抗剂的新型嵌合肽可产生脊髓上部抗痛觉效应，并降低小鼠的急性耐受性。

Biochimie Pub Date : 2024-08-13 DOI: 10.1016/j.biochi.2024.08.010

Bing Wu, Songxia Cheng, Fuyan Liu, Jia Wei, Yongling Liu, Teng Qian, Jiali Ding, Biao Xu, Jie Wei

{"title":"Novel chimeric peptides based on endomorphins and ghrelin receptor antagonist produced supraspinal antinociceptive effects with reduced acute tolerance in mice.","authors":"Bing Wu, Songxia Cheng, Fuyan Liu, Jia Wei, Yongling Liu, Teng Qian, Jiali Ding, Biao Xu, Jie Wei","doi":"10.1016/j.biochi.2024.08.010","DOIUrl":"10.1016/j.biochi.2024.08.010","url":null,"abstract":"It is widely recognized that developing bi- or multifunctional opioid compounds could offer a valuable approach to pain management with fewer side effects compared to single-target compounds. In this study, we designed and characterized two novel chimeric peptides, EM-1-DLS and EM-2-DLS, incorporating endomorphins (EMs) and the ghrelin receptor antagonist [D-Lys3]-GHRP-6 (DLS). Functional assays demonstrated that EM-1-DLS and EM-2-DLS acted as κ-opioid receptor (κ-OR)-preferring agonists, weak μ-opioid receptors (μ-OR) and ghrelin receptor (GHSR) agonists. Upon intracerebroventricular (i.c.v.) administration in mice, both EM-1-DLS and EM-2-DLS exhibited dose- and time-dependent antinociceptive effects in the tail withdrawal test. EM-1-DLS demonstrated the highest antinociceptive potency among the peptides, with an ED50 approximately 8-fold greater than EM-1, while EM-2-DLS showed comparable effects to EM-2. The antinociceptive actions of EM-1-DLS involved activation of GHS-R1α, μ-OR, and κ-OR, whereas EM-2-DLS acted via GHS-R1α, δ-OR, and κ-OR pathways. Additionally, acute antinociceptive tolerance was investigated, revealing that EM-1-DLS induced a tolerance ratio of 2.33-fold, significantly lower than the 5.19-fold ratio induced by EM-1. Cross-tolerance ratios between the chimeric peptides and EMs ranged from 0.92 to 1.76, indicating reduced tolerance compared to EMs alone. These findings highlight the potential of these chimeric peptides to mitigate pain with diminished tolerance development, suggesting a promising strategy for the development of new analgesic therapies with improved safety profiles.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Unveiling the mechanism of hesperidin-induced LdTopI-mediated cell death pathway in protozoan parasite Leishmania donovani. 揭示原生动物寄生虫唐氏利什曼原虫中橙皮甙诱导 LdTopI 介导的细胞死亡途径的机制。

Biochimie Pub Date : 2024-08-10 DOI: 10.1016/j.biochi.2024.08.008

Swati Lamba, Priyanka Mazire, Amit Roy

{"title":"Unveiling the mechanism of hesperidin-induced LdTopI-mediated cell death pathway in protozoan parasite Leishmania donovani.","authors":"Swati Lamba, Priyanka Mazire, Amit Roy","doi":"10.1016/j.biochi.2024.08.008","DOIUrl":"10.1016/j.biochi.2024.08.008","url":null,"abstract":"Unicellular protozoan parasite Leishmania donovani is the causative agent for visceral leishmaniasis (VL) or Kala-azar, a neglected fatal parasitic disease. The conventional treatment of VL consists of therapeutic agents having several shortcomings such as toxicity, high cost, efficacy variance and increased drug resistance. Therefore, there is a desperate need to develop an effective treatment against the parasite. Previous reports suggested that flavonoids can inhibit the enzyme Leishmania donovani DNA topoisomerase I (LdTopILS). Therefore, for the first time in this present study, we divulge HSP (one of the natural sources of flavonoids), as a potent natural antileishmanial compound with efficacy in BALB/c mice at 20 mg/kg of body weight, inhibits LdTopILS at 97 % of its activity at 160 μM in preincubation condition (competitively). It binds with free enzyme and does not allow it to bind with the substrate DNA. Moreover, HSP does not stabilize DNA-topoisomerase I cleavable complex. Thus, HSP acts a catalytic topoisomerase I inhibitor, which inhibits complete activity by binding with Lys269 and Thr411 of large subunit of the enzyme. On the other hand, HSP induces the topo I-mediated programmed cell death process by the formation of cellular reactive oxygen species, resulting in depolarization of mitochondrial membrane potential, followed by fragmentation of nuclear DNA. Therefore, the present study illuminates a natural flavonoid that in future might be a promising lead for the treatment of VL.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141918365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In silico-driven identification and experimental confirmation of antifungal proteins (AFPs) against Candidaalbicans. 针对白色念珠菌的抗真菌蛋白（AFPs）的硅学鉴定和实验确认。

Biochimie Pub Date : 2024-08-10 DOI: 10.1016/j.biochi.2024.08.007

Jyoti Sankar Prusty, Awanish Kumar

{"title":"In silico-driven identification and experimental confirmation of antifungal proteins (AFPs) against Candidaalbicans.","authors":"Jyoti Sankar Prusty, Awanish Kumar","doi":"10.1016/j.biochi.2024.08.007","DOIUrl":"10.1016/j.biochi.2024.08.007","url":null,"abstract":"Mycoses infect millions of people annually across the world. The most common mycosis agent, Candida albicans is responsible for a great deal of illness and death. C. albicans infection is becoming more widespread and the current antifungals polyenes, triazoles, and echinocandins are less efficient against it. Investigating antifungal peptides (AFPs) as therapeutic is gaining momentum. Therefore, we used MALDI-TOF/MS analysis to identify AFPs and protein-protein docking to analyze their interactions with the C. albicans target protein. Some microorganisms with strong antifungal action against C. albicans were selected for the isolation of AFPs. Using MALDI-TOF/MS, we identified 3 AFPs Chitin binding protein (ACW83017.1; Bacillus licheniformis), the bifunctional protein GlmU (BBQ13478.1; Stenotrophomonas maltophilia), and zinc metalloproteinase aureolysin (BBA25172.1; Staphylococcus aureus). These AFPs showed robust interactions with C. albicans target protein Sap5. We deciphered some important residues in identified APFs and highlighted interaction with Sap5 through hydrogen bonds, protein-protein interactions, and salt bridges using protein-protein docking and MD simulations. The three discovered AFPs-Sap5 complexes exhibit different levels of stability, as seen by the RMSD analysis and interaction patterns. Among protein-protein interactions, the remarkable stability of the BBQ25172.1-2QZX complex highlights the role of salt bridges and hydrogen bonds. Identified AFPs could be further studied for developing successful antifungal candidates and peptide-based new antifungal therapeutic strategies as fresh insights into addressing antifungal resistance also.","PeriodicalId":93898,"journal":{"name":"Biochimie","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141972460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Insight into the transcriptional regulation of key genes involved in proline metabolism in plants under osmotic stress. 渗透胁迫下植物脯氨酸代谢关键基因转录调控的深入研究

Biochimie Pub Date : 2024-08-08 DOI: 10.1016/j.biochi.2024.08.006

Shengjie Yan, Meng Zhan, Zhi Liu, Xianwen Zhang

引用次数: 0