155 results
Search Results
2. OsNAC2 regulates seed dormancy and germination in rice by inhibiting ABA catabolism.
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Zhao, Fankai, Ma, Qun, Li, Yingjiang, Jiang, Meihe, Zhou, Zhongjing, Meng, Shuan, Peng, Yan, Zhang, Jianhua, Ye, Nenghui, and Liu, Bohan
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GERMINATION , *SEED dormancy , *ABSCISIC acid , *DORMANCY in plants , *SEEDS , *GENETIC regulation , *PLANT life cycles , *METABOLIC regulation , *RICE seeds - Abstract
Seed dormancy and germination determine the beginning of the life cycle of plants, and the phytohormone ABA plays a crucial role in regulation of seed dormancy and germination. However, the upstream regulatory mechanism of ABA metabolism during dormancy releasing is still remain elusive. In this paper, we present a novel mechanism of OsNAC2 in controlling ABA metabolism and regulation of seed dormancy. OsNAC2 highly expressed during seed development and germination, and overexpression of OsNAC2 strengthened seed dormancy and suppressed germination. Moreover, exogenous phytohormone treatment showed that OsNAC2 acted upstream of GA signaling and downstream of ABA signaling. Additionally, overexpression of OsNAC2 inhibited ABA degradation and increased ABA content during early germination. Further molecular analysis revealed that OsNAC2 directly bound to the ABA metabolism genes promoter and inhibits their transcription in rice protoplasts. These finding could help us explain the genetic regulation mechanism of ABA metabolism during dormancy release and germination in rice. • OsNAC2 exhibits high expression levels in ungerminated rice seed embryos, followed by a rapid decline during germination. • Overexpressing OsNAC2 inhibits ABA degradation, maintaining elevated ABA during dormancy release. • OsNAC2 orchestrates hormone responses, including GA, ABA and JA pathways. • OsNAC2 directly binds to the promoters of ABA metabolism genes, thereby exerting transcriptional repression in rice. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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3. Fluorofenidone enhances cardiac contractility by stimulating CICR and CaV1.2.
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Ávila, Guillermo
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PULMONARY fibrosis , *SARCOPLASMIC reticulum , *CARDIOVASCULAR agents , *CONTRACTILITY (Biology) , *LIVER failure , *INTRACELLULAR calcium , *PHYSIOLOGY - Abstract
Fluorofenidone (AKF-PD) is a novel pyridone derivative that inhibits fibrosis and inflammation in many tissues. Accordingly, it has been effective in disease models, such as liver failure, nephropathy, and pulmonary fibrosis. However, its potential role in cardiac physiology and pathology has yet to be elucidated. Thus, this paper investigated a possible functional impact of AKF-PD on adult rat cardiac myocytes. Cells were kept in culture for 1–2 days under either control conditions or the presence of AKF-PD (500 μM). They were next examined concerning cell contractility, intracellular Ca2+ homeostasis, and activity of voltage-gated Ca2+ channels. Remarkably, AKF-PD enhanced the percentage of cell shortening and rates of both contraction and relaxation by nearly 100%. A stimulus in Ca2+-induced Ca2+ release (CICR) most likely accounts for these effects because AKF-PD also increased the magnitude of electrically evoked Ca2+ transients. Of note, the compound did not alter the peak value of caffeine-elicited Ca2+ transients, indicating stimulation of CICR at constant sarcoplasmic reticulum Ca2+ load. Since CICR is triggered by the entry of Ca2+ through Ca V 1.2 (I Ca), a possible effect on these Ca2+ channels was also investigated. AKF-PD increased the magnitude of both I Ca and maximal macroscopic Ca2+ conductance (G max) by about 50%. However, no differences were found in either voltage dependence of inactivation or the amount of maximal immobilization-resistant charge movement (Q max). Thus, the effect on I Ca could be explained by a higher channel's open probability (P o) rather than a greater abundance of channel proteins. Additional data indicate that AKF-PD reduces the rate of Ca2+ extrusion in the presence of caffeine, suggesting inhibition of the Na/Ca exchanger. Overall, these results indicate that AKF-PD upregulates the P o of Ca V 1.2 and then sequentially enhances I Ca , CICR, and contractility. Therefore, the novel compound is also a candidate to be tested in cardiac disease models. • Fluorofenidone (AKF-PF) is a novel anti-fibrotic and anti-inflammatory compound. • Here, its possible influence on the physiology of cardiac myocytes was assessed. • AKF-PF exerted a chronic upregulation of voltage-gated Ca2+ channels (Ca V 1.2). • The latter effect, in turn, enhances intracellular Ca2+ release and contractility. • These findings greatly improve the potential of AKF-PF as a cardiovascular agent. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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4. Impact of antipsychotics and antidepressants drugs on long QT syndrome induction related to hERG channel dysfunction: A systematic review.
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Nemati, Marzieh, Hosseinzadeh, Zahra, Nemati, Fatemeh, and Ebrahimi, Bahareh
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LONG QT syndrome , *ANTIDEPRESSANTS , *ANTIPSYCHOTIC agents , *DISEASE risk factors , *ARIPIPRAZOLE - Abstract
QT prolongation is one of the main unwanted cardiac effects caused by drugs, such as anti-psychotics and anti-depressants, inducing mainly via hERG channel dysfunction. The precise and underlying mechanism of adverse effects on hERG channel are still indecisive, but these effects limit their use in patients with cardiac risk factors. The aim of this review was studying mechanism of Long-term QT syndrome induction via hERG channel dysfunction by these Drugs. Search was performed in PubMed, and Scopus. All human, animals, and cell lines studies, English and full text publications were included. Among 1280 papers, 23 studies were eligible for more assessments. Quality of studies cheeked by two researchers independently. most of studies were done on anti-psychotic drugs, especially typical class. Most used investigated method to long-term QT induction was patch clamp. results suggests in susceptible cases with heart risk factors, these drugs should be taken with caution and monitored. • Addressing one of the underling mechanisms of hERG channel dysfunction related to long-term QT syndrome. • Determining that hERG channel dysfunction is the main mechanism in inducing LQTS of anti-psychotic and anti-depressant drugs. • Suggesting that these drugs should be taken with caution and monitoring in susceptible cases with heart risk factors. [ABSTRACT FROM AUTHOR]
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- 2023
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5. Stability of specific personality network features corresponding to openness trait across different adult age periods: A machine learning analysis.
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Zhi, Shengwen, Zhao, Wentao, Wang, Ruiping, Li, Yue, Wang, Xiao, Liu, Sha, Li, Jing, and Xu, Yong
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FUNCTIONAL magnetic resonance imaging , *MACHINE learning , *AGE groups , *PERSONALITY , *PERSONALITY questionnaires - Abstract
The functional connectivity patterns of the brain during resting state are closely related to an individual's cognition, emotion, behavior, and social interactions, making it an important research method to measure personality traits in an unbiased way, replacing traditional paper-and-pencil tests. However, due to the dynamic nature of the brain, whether the changes in functional connectivity caused by age can stably map onto personality traits has not been previously investigated. This study focuses on whether network features that are significantly related to personality traits can effectively distinguish subjects with different personality traits, and whether these network features vary across different periods of adulthood. The study included 343 healthy adult participants, divided into early adulthood and middle adulthood groups according to the age threshold of 35. Resting-state functional magnetic resonance imaging (fMRI) and the Big Five personality questionnaire were collected. we investigated the relationship between personality traits and intrinsic whole-brain functional connectome. We then used support vector machine (SVM) to evaluate the performance of personality network features in distinguishing subjects with high and low scores in the early-adulthood sample, and cross-validated in the mid-adulthood sample. Additionally, edge-based analysis (NBS) was used to explore the stability of personality networks across the two age samples. Our results show that the network features corresponding to openness personality trait are stable and can effectively differentiate subjects with different scores in both age samples. Furthermore, this study found that these network features vary to some extent across different periods of adulthood. These findings provide new evidence and insights into the application of resting-state functional connectivity patterns in measuring personality traits and help us better understand the dynamic characteristics of the human brain. • Application of resting-state functional connectivity patterns in measuring personality traits. • The network features corresponding to openness personality trait are stable. • Network features vary to some extent across different periods of adulthood. [ABSTRACT FROM AUTHOR]
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- 2023
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6. Survey of oligoethylene glycol-based self-assembled monolayers on electrochemical aptamer-based sensor in biological fluids.
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Son, Kon, Uzawa, Takanori, Ito, Yoshihiro, Kippin, Tod, Plaxco, Kevin W., and Fujie, Toshinori
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ELECTROCHEMICAL sensors , *BIOSENSORS , *MONOMOLECULAR films , *APTAMERS , *SIGNAL-to-noise ratio , *SENSOR placement , *ETHYLENE glycol - Abstract
The ability to monitor levels of endogenous markers and clearance profiles of drugs and their metabolites can improve the quality of biomedical research and precision with which therapies are individualized. Towards this end, electrochemical aptamer-based (EAB) sensors have been developed that support the real-time monitoring of specific analytes in vivo with clinically relevant specificity and sensitivity. A challenge associated with the in vivo deployment of EAB sensors, however, is how to manage the signal drift which, although correctable, ultimately leads to unacceptably low signal-to-noise ratios, limiting the measurement duration. Motivated by the correction of signal drift, in this paper, we have explored the use of oligoethylene glycol (OEG), a widely employed antifouling coating, to reduce the signal drift in EAB sensors. Counter to expectations, however, when challenged in 37 °C whole blood in vitro , EAB sensors employing OEG-modified self-assembled monolayers exhibit both greater drift and reduced signal gain, compared with those employ a simple, hydroxyl-terminated monolayer. On the other hand, when EAB sensor was prepared with a mix monolayer using MCH and lipoamido OEG 2 alcohol, reduced signal noise was observed compared to the same sensor prepared with MCH presumably due to improved SAM construction. These results suggest broader exploration of antifouling materials will be required to improve the signal drift of EAB sensors. • Signal drift limits EAB sensor's measurement duration in vivo. • Oligoethylene glycol was employed as SAM to reduce the signal drift in EAB sensors. • In blood, EAB sensors with OEG SAM exhibit greater drift and reduced signal gain. • EAB sensor prepared with MCH and OEG mix monolayer reduced signal noise. • In vivo , drift data of mix monolayer showed similar trends. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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7. GAREM1 is involved in controlling body mass in mice and humans.
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Nishino, Tasuku, Abe, Takaya, Kaneko, Mari, Yokohira, Masanao, Yamakawa, Keiko, Imaida, Katsumi, and Konishi, Hiroaki
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MICE , *ADAPTOR proteins , *SHORT stature , *CELL receptors , *BODY size , *KNOCKOUT mice - Abstract
The adaptor protein GAREM has two subtypes. Each is involved in Erk activation signaling downstream of the cell growth factor receptor in cultured cells. Regarding their role in individual animals, we have previously reported that mice deficient in GAREM2, which is highly expressed in the brain, exhibit emotional changes. In this paper, we report an amino acid substitution mutation (K291R) in GAREM1, in a patient with idiopathic short stature, which indicates that the mutant exhibits dominant-negative properties. The GAREM K291R mutant did not promote Erk activation in EGF-stimulated cultured cells. Similar features were also observed in cells in which GAREM1 expression was suppressed by genome editing; along with Erk, phosphorylation of S6 kinase and 4EBP1, whose activation is necessary for cell proliferation and biological growth, were inhibited Furthermore, we generated mice deficient in GAREM1 and showed that the mutant mice are lighter in weight. Overall, the results of this paper suggest that GAREM1 is required for normal growth and for maintaing average body size in humans and mice. • GAREM1 K291R mutation was found in patients with idiopathic short stature. •GAREM1 K291R mutant had reduced ability to transmit cell growth factor signals. •Cultured cells that eliminated GAREM1 expression by genome editing grew slower. •GAREM1 knockout mice had less body weight compared to wild type. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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8. Designing of various biosensor devices for determination of apoptosis: A comprehensive review.
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Akçapınar, Rumeysa, Garipcan, Bora, Goodarzi, Vahabodin, and Uzun, Lokman
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DEATH receptors , *APOPTOSIS , *BIOSENSORS , *CELL receptors , *DRUG efficacy , *CELL death , *SUSTAINABLE design - Abstract
Apoptosis is a type of cell death caused by the occurrence of both pathological and physiological conditions triggered by ligation of death receptors outside the cell or triggered by DNA damage and/or cytoskeleton disruption. Timely monitoring of apoptosis can effectively help early diagnosis of related diseases and continuous assessment of the effectiveness of drugs. Detecting caspases, a protease family closely related to cellular apoptosis, and its identification as markers of apoptosis is a popular procedure. Biosensors are used for early diagnosis and play a very important role in preventing disease progression in various body sections. Recently, there has been a widespread increase in the desire to use materials made of paper (e.g. nitrocellulose membrane) for Point-of-Care (POC) testing systems since paper and paper-like materials are cheap, abundant and degradable. Microfluidic paper-based analytical devices (μPADs) are highly promising as they are cost-effective, easy to use, fast, precise and sustainable over time and under different environmental conditions. In this review, we focused our efforts on compiling the different approaches on identifying apoptosis pathway while giving brief information about apoptosis and biosensors. This review includes recent advantages in biosensing techniques to simply determine what happened in the cell life and which direction it would continue. As a conclusion, we believed that the review may help to researchers to compare/update the knowledge about diagnosis of the apoptosis pathway while reminding the basic definitions about the apoptosis and biosensor technologies. [Display omitted] • Detecting caspases as markers of apoptosis • Cost-effective, easy to use, fast, precise and sustainable sensor designs • Compiling the different approaches on identifying apoptosis pathway • Brief information about apoptosis and biosensors • Biosensing techniques for determining what happened/direction in the cell life • Update the knowledge about diagnosis of the apoptosis pathway [ABSTRACT FROM AUTHOR]
- Published
- 2021
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9. Design of single-domain VHH antibodies to increase the binding activity in SPR amine coupling.
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Hirao, Atsunori, Nagatoishi, Satoru, Ikeuchi, Emina, Yamawaki, Tsukushi, Mori, Chinatsu, Nakakido, Makoto, and Tsumoto, Kouhei
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IMMUNOGLOBULINS , *SURFACE plasmon resonance , *BINDING sites , *AMINES , *AMINE oxidase , *STRUCTURAL stability , *ALANINE - Abstract
Single-domain antibodies, or VHH, nanobodies, are attractive tools in biotechnology and pharmaceuticals due to their favorable biophysical properties. Single-domain antibodies have potential for use in sensing materials to detect antigens, and in this paper, we propose a generic design strategy of single-domain antibodies for the highly efficient use of immobilized antibodies on a sensing substrate. Amine coupling was used to immobilize the single-domain antibodies on the substrate through a robust covalent bond. First, for two model single-domain antibodies with lysines at four highly conserved positions (K48, K72, K84, and K95), we mutated the lysines to alanine and measured the binding activity of the mutants (the percentage of immobilized antibodies that can bind antigen) using surface plasmon resonance. The two model single-domain antibodies tended to have higher binding activities when K72, which is close to the antigen binding site, was mutated. Adding a Lys-tag to the C-terminus of single-domain antibodies also increased the binding activity. We also mutated the lysine for another model single-domain antibodies with the lysine in a different position than the four residues mentioned above and measured the binding activity. Thus, single-domain antibodies immobilized in an orientation accessible to the antigen tended to have a high binding activity, provided that the physical properties of the single-domain antibodies themselves (affinity and structural stability) were not significantly reduced. Specifically, the design strategy of single-domain antibodies with high binding activity included mutating the lysine at or near the antigen binding site, adding a Lys-tag to the C-terminus, and mutating a residue away from the antigen binding site to lysine. It is noteworthy that mutating K72 close to the antigen binding site was more effective in increasing the binding activity than Lys-tag addition, and immobilization at the N-terminus close to the antigen binding site did not have such a negative effect on the binding activity compared to immobilization at the K72. • Model sdAbs mutants were immobilized by amine coupling and binding activities were measured by surface plasmon resonance. • Mutation of K72, one of the highly conserved lysines in sdAbs, increased binding activity after immobilization unless it destabilized the structure. • Mutation of K72 was more effective than N-terminal capping or addition of a Lys-tag to the C-terminus in designing sdAbs with high binding activity. • Mutating a residue away from the antigen binding site to lysine increased the binding activity of sdAbs. [ABSTRACT FROM AUTHOR]
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- 2023
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10. Comparison of anti-tumor activities and underlying mechanisms of glucuronomannan oligosaccharides and its sulfated derivatives on the hepatocarcinoma Huh7.5 cells.
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He, Xinyue, Chen, Fen, Lu, Chenghui, Wang, Sanying, Mao, Genxiang, Jin, Weihua, and Zhong, Weihong
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ANTINEOPLASTIC agents , *STRUCTURE-activity relationships , *PI3K/AKT pathway , *DEGREE of polymerization , *POLYSACCHARIDES , *OLIGOSACCHARIDES - Abstract
Hepatocellular carcinoma (HCC) is an aggressive tumor triggered by various factors such as virus infection and alcohol abuse. Glucuronomannan polysaccharide (Gx) is a subtype of fucoidans that possesses many bioactivities, but its anti-tumor activities in HCC have not been reported. In this paper, the anti-tumor effects of glucuronomannan oligosaccharides (Gx) and its sulfated derivatives (GxSy) on hepatocarcinoma Huh7.5 cells were investigated. The anti-proliferation, anti-metastasis activities, and underlying mechanism of Gx and GxSy on Huh7.5 cells were analyzed and compared by MTT, wound healing, transwell, and western blotting assays, respectively. Results showed that the best anti-proliferation effects were G4S1 and G4S2 among 13 drugs, which were 38.67% and 30.14%, respectively. The cell migration rates were significantly inhibited by G2S1, G4S2, G6S2, and unsulfated Gn. In addition, cell invasion effects treated with G4S1, G4S2, and G6S1 decreased to 48.62%, 36.26%, and 42.86%, respectively. Furthermore, sulfated G4 regulated the expression of (p-) FAK and MAPK pathway, and sulfated G6 down-regulated the MAPK signaling pathway while activating the PI3K/AKT pathway. On the contrary, sulfated G2 and unsulfated Gx had no inhibited effects on the FAK-mTOR pathway. These results indicated that sulfated Gx derivatives have better anti-tumor activities than unsulfated Gx in cell proliferation and metastasis process in vitro , and those properties depend on the sulfation group levels. Moreover, degrees of polymerization of Gx also played a vital role in mechanisms and bioactivities. This finding shows the structure-activity relationship for developing and applying the marine oligosaccharide candidates. • The anti-tumor activities of glucuronomannan oligosaccharides (Gx) and its sulfated derivatives (GxSy) were determined. • The effects of different degrees of polymerization of Gx on the FAK-mTOR signaling pathways were detected. • The effects of sulfation levels of GxSy on the FAK-mTOR signaling pathways were analyzed. [ABSTRACT FROM AUTHOR]
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- 2023
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11. Self-assembled porphyrin-based photosensitizer nanomicelles for enhanced photodynamic therapy.
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Cheng, Shanxia and Li, Jianfen
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PHOTODYNAMIC therapy , *PHOTOSENSITIZERS , *OPTICAL properties , *MICELLES , *PORPHYRINS - Abstract
Preparation of a supermacromolecular photosensitizer that can stay in the tumor site and exhibits high photoconversion efficiency is useful for improving the efficacy of tumor photodynamic therapy (PDT). In this paper, we prepared tetratroxaminobenzene porphyrin (TAPP) loaded biodegradable silk nanospheres (NSs) and characterized their morphology, optical properties and the singlet oxygen-generating capacity. On this basis, the effect of in vitro photodynamic killing efficacy by as-prepared nanometer micelles was evaluated and the tumor retention ability and tumor killing effect of the nanometer micelles were verified by the co-culture of photosensitizer micelle and tumor cells. The results show that tumor cells were killed well under 660 nm laser irradiation even at a lower concentration of as-prepared TAPP NSs. In addition, due to the excellent safety of as-prepared nanomicelle, they exhibit great potential applications in improved tumor PDT. • Tetratroxaminobenzene porphyrin loaded biodegradable silk nanospheres (NSs) were fabricated photodynamic therapy (PDT). • The self-assembled NSs exhibit improved singlet oxygen-generating capacity and a high tumor inhibition rate. • Other than outstanding PDT performances, silk-based NSs exhibit excellent biocompatibility and safety in vivo. [ABSTRACT FROM AUTHOR]
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- 2023
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12. Ensitrelvir is effective against SARS-CoV-2 3CL protease mutants circulating globally.
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Kawashima, Sho, Matsui, Yuki, Adachi, Takumi, Morikawa, Yuji, Inoue, Kae, Takebayashi, Shiori, Nobori, Haruaki, Rokushima, Masatomo, Tachibana, Yuki, and Kato, Teruhisa
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SARS-CoV-2 , *SARS-CoV-2 Omicron variant , *COVID-19 - Abstract
The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a public health concern worldwide. Ensitrelvir (S-217622) has been evaluated as an antiviral treatment for COVID-19, targeting SARS-CoV-2 3C-like protease (3CLpro). Ensitrelvir has been reported to have comparable antiviral activity against some of the SARS-CoV-2 variants: alpha, beta, gamma, delta, and omicron (BA.1.18). In this paper, we describe that ensitrelvir is effective against newly emerging SARS-CoV-2 variants and globally prevalent 3CLpro mutations. Ensitrelvir exhibited comparable antiviral activity against SARS-CoV-2 variants, including recently emerging ones: omicron (BA1.1, BA.2, BA.2.75, BA.4, BA.5, BQ.1.1, XBB.1, and XE), mu, lambda, and theta. Genetic surveillance of SARS-CoV-2 3CLpro, the target of ensitrelvir, was conducted using a public database and identified 11 major 3CLpro mutations circulating globally (G15S, T21I, T24I, K88R, L89F, K90R, P108S, P132H, A193V, H246Y, and A255V). The 3CLpro mutation from proline to histidine at amino acid position 132 was especially identified in the omicron variant, with prevalence of 99.69%. Enzyme kinetic assay revealed that these 3CLpro mutants have enzymatic activity comparable to that of the wild type (WT). Next, we assessed the inhibitory effect of ensitrelvir against mutated 3CLpro, with it showing inhibitory effects similar to that against the WT. These in vitro data suggest that ensitrelvir will be effective against currently circulating SARS-CoV-2 variants, including omicron variants and those carrying 3CLpro mutations, which emerging novel SARS-CoV-2 variants could carry. • Ensitrelvir showed comparable antiviral activity against various SARS-CoV-2 variants. • Genetic surveillance of SARS-CoV-2 3CLpro revealed 11 major 3CLpro mutations. • The IC 50 s of ensitrelvir against these mutants were similar to those of the wild type. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
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13. Reactive oxygen species (ROS), oxygen radicals and antioxidants: Where are we now, where is the field going and where should we go?
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Halliwell, Barry
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REACTIVE oxygen species , *STABLE isotopes , *HUMAN biology , *VITAMIN E , *DIETARY supplements , *CELLULAR signal transduction - Abstract
The field of oxygen free radicals, antioxidants and reactive oxygen species (ROS) has exploded in the past few decades, and BBRC has published several seminal papers. ROS can cause oxidative damage, but also play fundamental roles in living organisms, in such processes as signal transduction and defence against pathogens. ROS underpin every aspect of human biology. Indeed, an endless stream of published papers refers to the biological roles of "ROS". Sadly, much of this work is mechanistically meaningless. To make progress, the detailed molecular mechanisms of action of ROS must be elucidated and appropriate methodology must be used to measure them and the oxidative damage that they can cause, as emphasized in a recent review by Murphy et al. Attention must also switch from clinical studies involving administration of high-dose supplements of vitamins E, C and β-carotene for the treatment or prevention of human disease into other promising diet-derived cytoprotective agents. One of them may be ergothioneine. [ABSTRACT FROM AUTHOR]
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- 2022
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14. Piperlongumine mitigates LPS-induced inflammation and lung injury via targeting MD2/TLR4.
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Tang, Yelin, Zhang, Wenxin, Wu, Liqin, Bai, Bin, Zheng, Bin, Li, Mengying, Tang, Yue, Zhu, Xiaona, Zhang, Yali, Wang, Yi, and Zhang, Bing
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LIPOPOLYSACCHARIDES , *LUNG injuries , *PNEUMONIA , *SURFACE plasmon resonance , *GENE expression , *CELL culture - Abstract
Acute lung injury (ALI) is a fatal acute inflammatory illness with restricted therapeutic choices clinically. Piperlongumine (PL) is recognized as an alkaloid separated from Piper longum L, which was suggested to exhibit multiple pharmacological activities (e.g., anti-inflammatory activity). However, the effects of PL on LPS-triggered ALI and its anti-inflammatory target remain unclear. This paper intended to assess the roles of PL in LPS-triggered ALI, as well as its underlying mechanism and target. In vivo, ALI was induced by intratracheal injection of LPS to evaluate protective effects of PL and assessed by the changes of histopathological. In vitro, the anti-inflammatory activity and mechanism of PL were investigated by ELISA, RT-qPCR, transcription factor enrichment analysis, Western blotting and Immunofluorescence assay. The binding affinity of PL to MD2 was analyzed using computer docking, surface plasmon resonance, ELISA and immunoprecipitation assay. It was reported here that PL treatment alleviated LPS-induced pulmonary damage, inflammatory cells infiltration and inflammatory response in mice. In culture cells, PCR array showed that PL significantly inhibited LPS-induced inflammatory cytokines, chemokines, and type I IFNs genetic expression, along with the inhibition of TAK1 and TBK1 pathway. It is noteworthy that PL is capable of straightly binding to MD2 and inhibiting MD2/TLR4 complex formation and TLR4 dimerization. As revealed from this study, PL directly binding to MD2 to block cytokines expression by inhibiting the activation of TAK1 and TBK1 pathway, which then exerted its pulmonary protective activity. Accordingly, PL may act as an underlying candidate for treating LPS-triggered ALI. • Piperlongumine inhibits LPS-induced inflammation through MyD88 and TRIF-dependent signaling. • MD2 is the anti-inflammatory target of piperlongumine. • Piperlongumine is a potential candidate for the treatment of acute lung injury. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
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15. New skin tissue engineering scaffold with sulfated silk fibroin/chitosan/hydroxyapatite and its application.
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Peifen, Ma, Mengyun, Li, Jinglong, Hu, Danqian, Li, Yan, Tao, Liwei, Xu, Han, Zhao, Jianlong, Da, Lingyan, Li, Guanghui, Zhao, and Zhiping, Wang
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TISSUE engineering , *SILK fibroin , *TISSUE scaffolds , *CELL culture , *CHITOSAN , *WOUND healing , *HYDROXYAPATITE , *SKIN , *HAIR follicles - Abstract
Repairing skin wounds has always been challenging in clinical practice. The new skin tissue engineering scaffold provides innovative ways to address these challenges with a good chance of success because of its stable mechanical properties, biodegradability, and antibacterial properties. This paper presents the fabrication and evaluation of a three-dimensional composite scaffold made with sulfated silk fibroin, chitosan, and hydroxyapatite (SSF/CS/HAP). An electron microscope shows that the scaffold has an aperture of 15–20 μm, while an absorption performance test shows that its expansion index reaches 779%. The co-culture of L929 cells and the CCK-8 experiments demonstrated good cell compatibility and low scaffold cytotoxicity, respectively. Meanwhile, in vivo experiments demonstrate that rats with SSF/CS/HAP scaffold-treated neck wounds heal faster. In the wound skin tissue of the SSF/CS/HAP scaffold group, immunohistochemistry indicates a more rapid and mature development of hair follicles. This study successfully developed a novel skin tissue engineering scaffold material with high moisture retention, high tissue compatibility, and low cytotoxicity, demonstrating its ability to improve wound repair with promising potential for tissue engineering applications. • Sulfation of silk fibroin improved the hydrophilicity and biocompatibility of silk fibroin. • Innovatively constructed a three-dimensional composite scaffold and verified its porous structure and good expansibility. • This new composite scaffold could significantly promote cell proliferation and wound healing in rats. [ABSTRACT FROM AUTHOR]
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- 2023
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16. Fluid-driven DNA stretching for single-molecule studies on chromatin-associated proteins.
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Heo, Wonje, Seo, Jeonghwan, Lee, Yoonhee, and Kim, Yoori
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DNA-protein interactions , *SINGLE molecules , *DNA , *PROTEINS , *PROTEIN-protein interactions - Abstract
There have been many attempts to understand the central principle of life mediated by DNA-protein interactions surrounding complex environments. Still, the mechanistic insight of individual protein functions has been lacking in traditional ensemble assays. Thus, techniques visualizing a single molecule have emerged to uncover the discrete roles of DNA-protein interactions and their biophysical properties. This paper will review the advances in single-molecule tools imaging long genomic DNA and their applications in studying dynamic protein interactions. We focus on the three representative techniques, including molecular combing, nanochannel confinement, and DNA curtain assays, which use fluid-driven force to elongate the individual DNA. We provide an integrated perspective and a direction for future use to those who want to observe single DNA molecules along with their cellular factor of interest and employ them for dissecting protein function. • Single-molecule techniques for imaging genomic DNA advance our understanding of genome structure and functions. • Fluid-driven DNA stretching benefits characterizing the dynamics of chromatin-associated proteins. • Integrating lithography with individual DNA imaging overcomes the limitations of the single-molecule observation process. • We propose a next generation single-molecule platform capable of sensing protein behavior on DNA through electronic signal. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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17. Callus formation in albino Wistar rats after femur fracture assessed by visible spectroscopy.
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Orban, Emese, Pap, Zsuzsanna, Micu, Andreea Maria, Sipos, Remus Sebastian, and Fechete, Radu
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OPTICAL spectroscopy , *FEMORAL fractures , *LABORATORY rats , *CALLUS , *FRACTURE healing , *TISSUES , *TISSUE culture - Abstract
Classical histological methods such as hematoxylin-eosin staining, have been, and in some areas still are, an important benchmark for the evaluation of biological tissues. However, the current method of assessment is primarily a qualitative assessment of the tissue under investigation. The aim of this paper is to contribute to the improvement of classical histological methods, by applying physical techniques that allow objective, quantitative data to be added to qualitative assessments, especially in areas where conflicting results are available. To this end, the effect of hypolipidemic medication on the callus formation process of normal bone and pathological osteoporotic bone was investigated. The study allowed us to associate UV-VIS spectroscopy wave number with specific hematoxylin-eosin staining of different types of bone tissue structures, the evolving structures in the callus formation process. This association allowed the quantitative assessment of the callusing process in ovariectomized (associated with pathological, osteoporotic bone) and non-ovariectomized (associated with normal bone) rats, with three groups - the control group, simvastatin-treated group, and fenofibrate-treated group. The study showed that in the non-ovariectomized groups both treatments delayed callus formation. In the ovariectomized groups, simvastatin delayed and fenofibrate promoted callus formation. • Fracture healing is dependent on the presence or absence of estrogen. • The inflammatory reaction is stronger in the ovariectomized rats. • Hypolipemiant treatment delays callus formation in the non-ovariectomized rats. • Fenofibrate treatment favors the callus formation process in ovariectomized rats. • Visible spectroscopy is a physical method to quantify bone healing. [ABSTRACT FROM AUTHOR]
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- 2022
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18. Structural and biochemical insights into the association between ERAP1 polymorphism and autoimmune diseases.
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Liu, Shuang, Lu, Jianghui, Wu, Jiaqi, Feng, Dongyan, Wang, Yanbing, Su, Xin, and Cao, Hao
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AUTOIMMUNE diseases , *MAJOR histocompatibility complex , *SINGLE nucleotide polymorphisms , *ENZYME specificity , *PROTEIN engineering , *MUTANT proteins , *GENETIC polymorphisms - Abstract
Autoimmune diseases afflict nearly 10% of the world's population and have a serious impact on survival and quality of life. Unfortunately, the specific pathogenesis of almost all autoimmune diseases is still unclear, with more research findings identifying some key pathogenic genes at the genetic level and several pathogenic inflammatory factor phenotypes. ERAP1 has been suggested as a potential therapeutic target for several autoimmune diseases, especially MHC-Ⅰ related. How the structure and antigenic peptide processing function of ERAP1 affect the pathogenesis of these autoimmune diseases needs to be elucidated more clearly. Genetic studies on single nucleotide polymorphism of ERAP1 provide a good bridge to better understand the relationship and pattern between ERAP1 structure, function, and disease. However, existing reviews have focused on the genetic association of ERAP1 SNPs with autoimmune diseases, and no one has specifically addressed how ERAP1 gene polymorphisms embodied at the protein level specifically mediate antigenic peptide editing and the development of multiple autoimmune diseases. In this paper, we present a comprehensive review of these ERAP1 SNPs associated with multiple autoimmune diseases, in particular the polymorphisms affecting their protein structure and enzyme function, and attempt to unravel the underlying structural and biochemical mechanisms by which ERAP1 affects the pathogenesis of multiple autoimmune diseases through the SNP-protein structure-function-disease relationship. This study will provide theoretical help and ideas for understanding the relationship between ERAP1 and autoimmune diseases and for drug design targeting wild-type and mutant proteins with different polymorphisms. • ERAP1 and its single nucleotide polymorphisms (SNPS) are believed to be associated with a variety of autoimmune diseases. • The genetic and protein structural diversity of ERAP1 will have an important impact on most autoimmune disease. • ERAP1 polymorphism affects self-expression, structural stability, interdomain interaction, enzyme activity and specificity. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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19. Regulating the mechanics of silk fibroin scaffolds promotes wound vascularization.
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Guo, Peng, Du, Pan, Zhao, Peng, Chen, Xue, Liu, Chenyang, Du, Yong, Li, Jiadai, Tang, Xiaoyu, Yang, Fengbo, and Lv, Guozhong
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SILK fibroin , *CELL migration , *CELL differentiation , *ENDOTHELIAL cells , *EXTRACELLULAR matrix , *WOUND healing - Abstract
Functional blood vessels are crucial to wound healing, and faster vascularization means faster tissue repair to some extent. Increasing numbers of pro-vascularization wound coverings are being developed and studied. Moreover, mechanical properties of the extracellular matrix can guide the behaviour of related cells to some degree. Studies have shown that the mechanical range of 1–7 kPa contributes to the differentiation of stem cells into endothelial cells and thus to the process of wound vascularization. Unfortunately, the regulatory mechanics of vascularizing wound coverings have been poorly studied. Silk fibroin (SF) has attracted much attention because of its good biocompatibility, degradability and adjustable mechanical properties. In this paper, silk scaffolds with mechanical properties of 2 kPa and 5.9 kPa were prepared by adjusting the mechanics of silk scaffolds in terms of freezing temperature and aligned structure. The mechanical properties of the 5.9 kPa aligned silk scaffold (ASS) showed good vascularization ability. By adjusting the intermediate conformation and physical structure of Silk fibroin (SF), the mechanical strength of the silk scaffold could be increased, enabling us to better understand the mechanical regulation mode. At the same time, the aligned structure of the aligned silk scaffold (ASS) promoted the migration and proliferation of cells related to wound repair to a certain extent. By adjusting the mechanical properties and physical structure of the material, an aligned silk scaffold with vascularization function was constructed, providing more possibilities for faster wound repair. • In this paper, silk scaffolds with mechanical properties of 2 kPa and 5.9 kPa were prepared by adjusting the mechanics of silk scaffolds in terms of freezing temperature and aligned structure. • By adjusting the intermediate conformation and physical structure of Silk fibroin (SF), the mechanical strength of the silk scaffold could be increased. • By adjusting the mechanical properties and physical structure of the material, an aligned silk scaffold with vascularization function was constructed, providing more possibilities for faster wound repair. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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20. Integrated information theory does not make plant consciousness more convincing.
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Mallatt, Jon, Taiz, Lincoln, Draguhn, Andreas, Blatt, Michael R., and Robinson, David G.
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INFORMATION theory , *CONSCIOUSNESS , *BOTANISTS , *COMMUNICATIONS research - Abstract
It has been proposed by some plant scientists that plants are cognitive and conscious organisms, although this is a minority view. Here we present a brief summary of some of the arguments against this view, followed by a critique of an article in this same issue of Biochemical and Biophysical Research Communications by Calvo, Baluska, and Trewavas (2020) that cites Integrated Information Theory (IIT) as providing additional support for plant consciousness. The authors base their argument on the assumptions that all cells are conscious and that consciousness is confined to life. However, IIT allows for consciousness in various nonliving systems, and thus does not restrict consciousness to living organisms. Therefore, IIT cannot be used to prove plant consciousness, for which there is neither empirical evidence nor support from other, neuron-based, theories of consciousness. • We discuss a concurrent paper by Calvo and coworkers that claims plants have consciousness. • That paper claims support from the well-known Integration Information Theory (IIT) of consciousness. • That paper also claims that consciousness is confined to living systems. • However, IIT attributes consciousness to many nonliving systems. • Therefore, IIT does not support plant consciousness as claimed. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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21. Lysosome exocytosis is required for mitosis in mammalian cells.
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Nugues, Charlotte, Rajamanoharan, Dayani, Burgoyne, Robert D., Haynes, Lee P., and Helassa, Nordine
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MITOSIS , *EXOCYTOSIS , *CELL division , *CHROMOSOME segregation , *LYSOSOMES , *CYTOKINESIS , *CELL membranes - Abstract
Mitosis, the accurate segregation of duplicated genetic material into what will become two new daughter cells, is accompanied by extensive membrane remodelling and membrane trafficking activities. Early in mitosis, adherent cells partially detach from the substratum, round up and their surface area decreases. This likely results from an endocytic uptake of plasma membrane material. As cells enter cytokinesis they re-adhere, flatten and exhibit an associated increase in surface area. The identity of the membrane donor for this phase of mitosis remains unclear. In this paper we demonstrate how lysosomes dynamically redistribute during mitosis and exocytose. Antagonism of lysosomal exocytosis by pharmacological and genetic approaches causes mitosis failure in a significant proportion of cells. We speculate that either lysosomal membrane or luminal content release, possibly both, are therefore required for normal mitosis progression. These findings are important as they reveal a new process required for successful cell division. • Mammalian mitosis involves extensive membrane remodelling. • The identity of the membrane donor during mitotic cell division remains unclear. • Inhibition of lysosomal exocytosis causes mitosis failure. • Lysosomal membrane and/or luminal content release are essential for mitosis progression. • These findings reveal a new process required for successful mammalian cell division. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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22. NCAPG promotes tumorigenesis of bladder cancer through NF-κB signaling pathway.
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Tang, Feng, Yu, Hua, Wang, Xia, Shi, Jiageng, Chen, Zhizhuang, Wang, Hao, Wan, Ziyu, Fu, Qiqi, Hu, Xuan, Zuhaer, Yisha, Liu, Tao, Yang, Zhonghua, and Peng, Jianping
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BLADDER cancer , *CELLULAR signal transduction , *CANCER cell proliferation , *NEOPLASTIC cell transformation , *URODYNAMICS , *CELL growth - Abstract
The non-SMC condensin I complex subunit G (NCAPG) is a subunit of the condensin complex, many studies have shown that NCAPG is aberrantly expressed in different tumors and closely associated with poor prognosis, but its role in bladder cancer is unclear. In this paper, we found that NCAPG expression was upregulated in bladder cancer in tumor-related databases, and further verified the expression of NCAPG in bladder cancer tissues as well as bladder cancer cell lines by tissue microarray, qPCR, and WB. Next, we explored the changes in bladder cancer cell proliferation as well as migration after NCAPG knockdown by cell growth curve, colony formation, soft agar assay, and xenograft model. Finally, we examined the changes in downstream signaling pathways after NCAPG knockdown using RNA-Seq, and we found that the NF-κB signaling pathway was inhibited with NCAPG gene knockdown, which was verified by luciferase reporter assay as well as WB. In conclusion, our results illustrate that NCAPG knockdown can inhibit the proliferation of bladder cancer cells through the NF-κB signaling pathway. This finding demonstrates that NCAPG could be a potential target for the treatment of bladder cancer. • This article firstly studied the role of NCAPG in bladder cancer. • It is demonstrated that NCAPG promotes tumor proliferation in bladder cancer by activating the NF-κB signal pathway. • The role of NCAPG in bladder cancer was demonstrated by in vitro and in vivo experiments. [ABSTRACT FROM AUTHOR]
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- 2022
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23. Isosteviol sodium attenuates high fat/high cholesterol-induced myocardial dysfunction by regulating the Sirt1/AMPK pathway.
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Mei, Ying, Hu, Hui, Deng, Liangjun, Sun, Xiaoou, and Tan, Wen
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HIGH-fat diet , *WESTERN immunoblotting , *SODIUM , *LIPID metabolism , *OXIDANT status - Abstract
A fat-rich diet triggers obesity, and promotes cardiomyocyte injury. Till now, no prior investigations suggested a beneficial role of Isosteviol Sodium (STVNa) in cardiac activity in high fat diet (HFD)-exposed obese rats. However, there is evidence that STVNa accelerates healing of multiple tissue injuries. Herein, we explored the underlying mechanism behind the STVNa-based protection against HFD-induced myocardial dysfunction (MCD) in a rat model of myocardial injury. We employed dosages of 1, 10, and 20 mg/kg STVNa to treat MCD in rats fed with a HFD. Based on our results, STVNa repressed MCD (as indicated by ecocardiographic analysis), myocardium function, pathological structure, and myocardial enzymes. Mechanistically, the STVNa-mediated protection against HFD-induced MCD involved inhibition of inflammation and oxidative stress. Furthermore, using Western blot analysis, we revealed that the critical members of the Sirt1/AMPK network were markedly activated in the STVNa-treated group, relative to HFD-fed controls. Collectively, these evidences suggested that the STVNa offered strong protection against HFD-induced MCD. Moreover, this effect was mediated by the activation of the Sirt1/AMPK network, which, in turn, promoted lipid metabolism. • The model of myocardial dysfunction (MCD) in a rat was established by high fat diet (HFD). • The paper results suggested that the therapeutic effect of STVNa was achieved via lowering of blood glucose levels in favor of enhancing metabolism. • Both AMPK and SIRT1 pathways were inhibited in the myocardium of STVNa-treated HFD rats. STVNa also improved the antioxidant capacity of myocardial tissue and inhibited inflammation by NF-κB signaling pathway. • STVNa has a good therapeutic effect on HFD-induced MCD. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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24. Measurement of intraluminal pH changes in the gastrointestinal tract of mice with gastrointestinal diseases.
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Sun, Yuanjie, Koyama, Yoshihisa, and Shimada, Shoichi
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GASTROINTESTINAL diseases , *INFLAMMATORY bowel diseases , *GASTROINTESTINAL contents , *GASTROINTESTINAL system , *PREVENTIVE medicine - Abstract
As a fundamental and essential property, gastrointestinal (GI) tract pH reflects its condition and changes in several GI diseases such as inflammatory bowel disease (IBD), gastritis, etc. As a result, accurately measuring the GI pH is crucial for treatment, diagnosis, and prevention of GI diseases and contributes to developing GI disease models for basic studies. However, among pH measuring studies with animal models, there is no reliable method that can reflect the value and changing trends of GI pH in actual patients. In the current study, we developed a fast, simple method with pH indicator paper to measure the GI pH changes with GI content in normal mice and mice with colitis or hepatitis. Results demonstrated that normal mice's mean GI pH values were between 6.0 and 8.0, which was consistent with previous reports. Furthermore, the GI pH of colitis and hepatitis model mice showed the same pattern of lower values in the intestine and higher values in the stomach compared with normal mice. Our simple and timesaving method can accurately measure the dramatic changes in the GI pH of mice with GI diseases and is suitable for measuring the pH of sticky liquids with limited volume. Given all the merits listed above, this method is helpful for further research. • A simple and timesaving method to measure gastrointestinal (GI) tract pH in mice. • GI pH changes in animal models reflect pH changes in actual patients. • First time to report GI pH changes in the hepatitis model mice. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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25. CircPDHX promotes prostate cancer cell progression in vitro and tumor growth in vivo via miR-497-5p/ACSL1 axis.
- Author
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Chen, Jia, Xie, Qitong, Miao, Weixian, Fan, Jianrui, Zhou, Xiaobo, and Li, Maozhang
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- *
TUMOR growth , *PYRUVATE dehydrogenase complex , *PROSTATE cancer , *CANCER invasiveness , *CANCER cells , *CIRCULAR RNA , *ANDROGEN receptors , *CELL migration - Abstract
Circular RNAs (circRNAs) have been proved could regulate many cancers, including prostate cancer (PCa). In this paper, we reconnoitered the roles of circRNA pyruvate dehydrogenase complex component X (circPDHX) in PCa. The circPDHX, microRNA (miR)-497-5p and acyl-CoA synthetase long chain family member 1 (ACSL1) contents were detected by quantitative real-time PCR and Western blot analysis. Cell proliferation was measured by cell counting kit-8 assay, 5-Ethynyl-2′-deoxyuridine assay, and colony formation assay. Cell migration was examined by wound healing assay. The apoptosis was detected by flow cytometry assay. The ELISA kits were applied to quantify the fatty acid metabolites. Furthermore, the interplay between miR-497-5p and circPDHX or ACSL1 was detected by dual-luciferase reporter assay and RIP assay. The role of circPDHX in PCa was supplementary substantiated in vivo. CircPDHX and ACSL1 contents were upregulated, and the miR-497-5p level was downregulated in PCa. CircPDHX deficiency attenuated PCa cell proliferation, migration, and fatty acid metabolites, while intensified cell apoptosis. CircPDHX bound to miR-497-5p to adjust ACSL1. Moreover, miR-497-5p inhibited the PCa progression by regulating ACSL1. In the meantime, circPDHX deficiency repressed PCa tumor growth in vivo. CircPDHX stimulated PCa development via miR-497-5p/ACSL1, which presented a new thought for PCa treatment. • CircPDHX was upregulated in PCa cells. • CircPDHX deficiency attenuated PCa cell progression and tumor growth. • CircPDHX sponged miR-497-5p. • MiR-497-5p targeted ACSL1. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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26. Representation of polysaccharide molecules by SNFG and 3D-SNFG methods——Take Potentilla anserina L polysaccharide molecule as an example.
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Ji, Tengqi and Zhang, Ji
- Subjects
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MOLECULES , *GLYCANS , *POLYSACCHARIDES , *MONOSACCHARIDES , *STRUCTURE-activity relationships , *MOLECULAR structure , *INFORMATION sharing - Abstract
With the continuous deepening of international research in the field of biology, more and more studies have found that polysaccharides have multiple biological functions, so that polysaccharides have gradually become the research objects of more and more scientists in the world, and a large number of relevant researchers have carried out Glycobiology research, most of the current research is on the separation, extraction, structural characterization and activity experiments of polysaccharides. However, at this stage, research on the structure-activity relationship of various polysaccharides extracted from plants is relatively rare, and the representation method of polysaccharide structures is not perfect, not unified, complicated in drawing, and not beautiful and convenient to read. The SNFG (Symbol Nomenclature For Glycans) method, which is the symbolic nomenclature of polysaccharides and the 3D-SNFG method, can solve the above problems well, and can use unified rules to describe and describe the molecular structure of polysaccharides, and the painting process is more convenient and more convenient. It is beautiful and makes it easier for readers to read. In this paper, the fern hemp polysaccharide molecule is taken as an example. After drawing it with chemoffice, SNFG and 3D-SNFG are used to describe it, and then compared. It is clear at a glance that the use of SNFG and 3D-SNFG methods has been widely recognized and accepted internationally, which can provide great convenience for sugar-related research and information exchange. • Characterization of polysaccharide structure by SNFG method. • Using the 3D-SNFG method to obtain a 3D ball and stick model of the polysaccharide molecule. • The SNFG method is beautiful and convenient. • Seeing the spatial structure and monosaccharide composition of polysaccharide molecules clearly. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
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27. The mechanism and clinical application of farnesyl diphosphate farnesyltransferase 1 in cancer metabolism.
- Author
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Li, Nanxin, Wang, Guojuan, Guo, Min, Zhu, Naicheng, and Yu, Wenyan
- Subjects
- *
CHOLESTEROL metabolism , *CLINICAL medicine , *METABOLIC reprogramming , *CANCER cell proliferation , *METABOLISM , *CANCER prevention , *HYDROXYCHOLESTEROLS - Abstract
Cancer poses a significant risk to human well-being. Among the crucial characteristics of cancer is metabolic reprogramming. To meet the relentless metabolic needs, cancer cells enhance cholesterol metabolism within the adverse tumor microenvironment. Reprograming cholesterol metabolism includes a series of modifications in the synthesis, absorption, esterification, and metabolites associated with cholesterol. These adjustments have a strong correlation with the proliferation, invasion, metastasis, and other characteristics of malignant tumors. FDFT1, also known as farnesyl diphosphate farnesyltransferase 1, is an enzyme crucial in the process of cholesterol biosynthesis. Its significant involvement in tumor metabolism has garnered considerable interest. The significance of FDFT1 in cancer metabolism cannot be overstated, as it actively interacts with cancer cells. This paper aims to analyze and consolidate the mechanism of FDFT1 in cancer metabolism and explore its clinical application. The goal is to contribute new strategies and targets for the prevention and treatment of cancer metabolism. • FDFT1: Bidirectional Regulation of Cancer Cell Proliferation and Metastasis. • Mechanism of FDFT1 in Cancer Metabolism:The downstream and upstream pathways. • Clinical Application of FDFT1 in Cancer Therapy and Prognosis. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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28. The tick Ixodes scapularis has five different GPCRs specifically activated by ACP (adipokinetic hormone/corazonin-related peptide).
- Author
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Hauser, Frank, Stebegg, Marisa, Al-Ribaty, Tara, Petersen, Lea B., Møller, Mads, Drag, Markus H., Sigurdsson, Haraldur H., Vilhelm, Martin J., Thygesen, Gedske, and Grimmelikhuijzen, Cornelis J.P.
- Subjects
- *
IXODES scapularis , *PEPTIDES , *LIMULIDAE , *G protein coupled receptors , *TICKS , *TICK-borne diseases , *SCORPION venom - Abstract
Insects have about 50 neuropeptide genes and about 70 genes, coding for neuropeptide G protein-coupled receptors (GPCRs). An important, but small family of evolutionarily related insect neuropeptides consists of adipokinetic hormone (AKH), corazonin, and AKH/corazonin-related peptide (ACP). Normally, insects have one specific GPCR for each of these neuropeptides. The tick Ixodes scapularis is not an insect, but belongs to the subphylum Chelicerata, which comprises ticks, scorpions, mites, spiders, and horseshoe crabs. Many of the neuropeptides and neuropeptide GPCRs occurring in insects, also occur in chelicerates, illustrating that insects and chelicerates are evolutionarily closely related. The tick I. scapularis is an ectoparasite and health risk for humans, because it infects its human host with dangerous pathogens during a blood meal. Understanding the biology of ticks will help researchers to prevent tick-borne diseases. By annotating the I. scapularis genome sequence, we previously found that ticks contain as many as five genes, coding for presumed ACP receptors. In the current paper, we cloned these receptors and expressed each of them in Chinese Hamster Ovary (CHO) cells. Each expressed receptor was activated by nanomolar concentrations of ACP, demonstrating that all five receptors were functional ACP receptors. Phylogenetic tree analyses showed that the cloned tick ACP receptors were mostly related to insect ACP receptors and, next, to insect AKH receptors, suggesting that ACP receptor genes and AKH receptor genes originated by gene duplications from a common ancestor. Similar duplications have probably occurred for the ligand genes, during a process of ligand/receptor co-evolution. Interestingly, chelicerates, in contrast to all other arthropods, do not have AKH or AKH receptor genes. Therefore, the ancestor of chelicerates might have lost AKH and AKH receptor genes and functionally replaced them by ACP and ACP receptor genes. For the small family of AKH, ACP, and corazonin receptors and their ligands, gene losses and gene gains occur frequently between the various ecdysozoan clades. Tardigrades, for example, which are well known for their survival in extreme environments, have as many as ten corazonin receptor genes and six corazonin peptide genes, while insects only have one of each, or none. [Display omitted] • The tick Ixodes scapularis is a vector for serious human diseases, such as Lyme. • G protein-coupled receptors (GPCRs) play a central role in the physiology of ticks. • GPCRs are also excellent drug targets to fight ticks. • Ticks have as many as five possible GPCR genes for the tick neuropeptide ACP. • We cloned these GPCRs and deorphanized them as being ACP receptors. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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29. Mdivi-1: Effective but complex mitochondrial fission inhibitor.
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Ahn, Seor I, Choi, Sung Kyung, Kim, Myoung Jun, Wie, Jinhong, and You, Jueng Soo
- Subjects
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DNA analysis , *MITOCHONDRIAL DNA , *RNA sequencing , *MITOCHONDRIA , *DNA methylation , *POLYMER networks , *EPIGENOMICS - Abstract
Mdivi-1, Mitochondrial DIVIsion inhibitor 1, has been widely employed in research under the assumption that it exclusively influences mitochondrial fusion, but effects other than mitochondrial dynamics have been underinvestigated. This paper provides transcriptome and DNA methylome-wide analysis for Mdivi-1 treated SH-SY5Y human neuroblastoma cells using RNA sequencing (RNA-seq) and methyl capture sequencing (MC-seq) methods. Gene ontology analysis of RNA sequences revealed that p53 transcriptional gene network and DNA replication initiation-related genes were significantly up and down-regulated, respectively, showing the correlation with the arrest cell cycle in the G1 phase. MC-seq, a powerful sequencing method for capturing DNA methylation status in CpG sites, revealed that although Mdivi-1 does not induce dramatic DNA methylation change, the subtle alterations were concentrated within the CpG island. Integrative analysis of both sequencing data disclosed that the p53 transcriptional network was activated while the Parkinson's disease pathway was halted. Next, we investigated several changes in mitochondria in response to Mdivi-1. Copy number and transcription of mitochondrial DNA were suppressed. ROS levels increased, and elevated ROS triggered mitochondrial retrograde signaling rather than inducing direct DNA damage. In this study, we could better understand the molecular network of Mdivi-1 by analyzing DNA methylation and mRNA transcription in the nucleus and further investigating various changes in mitochondria, providing inspiration for studying nuclear-mitochondrial communications. • First reported Mdivi-1-induced DNA methylome shows Mdivi-1 dwindles CGI methylation. • RNA/DNA-methyl sequencing integration unveils Mdivi-1's therapeutic mechanism. • Mdivi-1 modulates retrograde signaling by ROS. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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30. Torsion affects the calculation of DNA twisting number.
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Yang, Huimin and Shi, Xuguang
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TORSION , *DNA , *DIFFERENTIAL geometry , *TOPOLOGICAL property , *BIOPHYSICS - Abstract
The topological properties of DNA have long been a focal point in biophysics. In the 1970s, White proposed that the topology of closed DNA double helix follows White's formula: L k = W r + T w. However, there has been controversy in the calculation of DNA twisting number, partly due to discrepancies in the definition of torsion in differential geometry. In this paper, we delved into a detailed study of torsion, revealing that the calculation of DNA twisting number should use the curve's geodesic torsion. Furthermore, we found that the discrepancy in DNA twisting numbers calculated using different torsion is N. This study elucidated the impact of torsion on the calculation of DNA twisting numbers, aiming to resolve controversies in the calculation of DNA topology and provided accurate computational methods and theoretical foundations for related research. • Both as a spatial curve and as a curve lying on a surface, the DNA helix axis is taken into account during the calculation of the twisting number. The torsion derived from each perspective varies. • We have clarified that the torsion mentioned in Fuller's works should refer to the geodesic torsion of the surface where the DNA helix axis resides. • The twisting number computed from the torsion of a surface curve differs from that of a spatial curve by a specific numerical factor. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
31. Spexin acts as a novel glucose-lowering factor in grass carp (Ctenopharyngodon idella).
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Zhang, Yingxin, Wang, Junli, Yang, Liping, Yan, Xiao, Qin, Chaobin, and Nie, Guoxing
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CTENOPHARYNGODON idella , *METABOLIC regulation , *GLYCOGEN phosphorylase , *WEIGHT loss , *GLUCOSE metabolism , *INSULIN , *PHOSPHORYLASES - Abstract
At present, the physiological roles of various hormones in fish glucose metabolism have been elucidated. Spexin, a 14-amino acids polypeptide, is highly conserved in many species and has functions such as reducing body weight and improving insulin resistance. In this paper, the open reading frame (ORF) of spx2 1 in grass carp (Ctenopharyngodon idella) was cloned, and the tissue distribution of spx1 and spx2 , their direct and indirect regulatory effects on glucose metabolism of grass carp were investigated. The ORF of spx2 gene in grass carp was 279 bp in length. Moreover, spx1 was highly expressed in the adipose tissue, while spx2 was highly expressed in the brain. In vitr o, SPX1 and SPX2 showed opposite effects on the glycolytic pathway in the primary hepatocytes. In vivo , intraperitoneal injection of SPX1 and SPX2 significantly reduced serum glucose levels and increased hepatopancreas glycogen contents. Meanwhile, SPX1 and SPX2 promoted the expression of key genes of glycolysis (pk) and glycogen synthesis (gys) in the hepatopancreas at 3 h post injection. As for indirect effects, 1000 nM SPX1 and SPX2 significantly increased insulin-mediated liver type phosphofructokinase (pfkla) mRNA expression and enhanced the inhibitory effects of insulin on glucose-6-phosphatase (g6pase), phosphoenolpyruvate carboxykinase (pepck), glycogen phosphorylase L (pygl) mRNA expression. Our results show that SPX1 and SPX2 have similar indirect effects on the regulation of glucose metabolism that enhance insulin activity, but they exhibit opposite roles in terms of direct effects. [Display omitted] • SPX1 and SPX2 showed opposite effects on the glycolytic pathway in vitro. • SPX1/2 play a hypoglycemic role in vivo in grass carp. • SPX1 promotes glycolysis and glycogen synthesis, and inhibits gluconeogenesis in vivo. • SPX2 promotes glycolysis and glycogen synthesis in vivo. • SPX1/2 promote insulin-induced glycolysis and glycogen synthesis, inhibit gluconeogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
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32. The structure of Deinococcus radiodurans transcriptional regulator HucR retold with the urate bound.
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Rho, SooHo, Jung, WeonSeok, Park, Jeong Kuk, Choi, Min Hee, Kim, MinJu, Kim, JooYoung, Byun, JiWon, Park, Taehyun, Lee, Byung Il, Wilkinson, Steven P., and Park, SangYoun
- Subjects
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DEINOCOCCUS radiodurans , *CARRIER proteins , *DNA folding , *URIC acid , *CRYSTAL structure - Abstract
HucR is a MarR family protein of Deinococcus radiodurans , which binds tightly to the intergenic region of HucR and the uricase gene to inhibit their expression. Urate (or uric acid) antagonizes the repressor function of HucR by binding to HucR to impede its association with the cognate DNA. The previously reported crystal structure of HucR was without the bound urate showing significant structural homology to other MarR structures. In this paper, we report the crystal structure of HucR determined with the urate bound. However, despite the fact that the urate is found at a site well-known to harbor ligands in other MarR family proteins, the overall HucR structure indicates that no significant change in structure takes place with the urate bound. Structure analysis further suggests that the urate interaction in HucR is mediated by histidine/glutamate side chains and ordered water molecules stabilized by various residues. Such interaction is quite unique compared to other known structural interactions between urate and its binding proteins. Furthermore, structural comparison of the apo- and the urate bound forms allows us to hypothesize that the Trp20-mediated water network in the apo-form stabilizes the proper HucR fold for cognate DNA binding, and that urate binding, also via Trp20, and the consequent reorganization of water molecules in the binding pocket, likely disrupts the DNA binding configuration to result in the attenuated DNA binding. • The MarR family Deinococcus radiodurans HucR acts as a transcriptional repressor. • However, urate (uric acid) antagonizes the repression by releasing the cognate DNA. • Here, we report the crystal structure of HucR with the bound urate molecule. • HucR's specific urate interaction is not observed in other urate binding proteins. • The structure suggests a mechanism for urate-induced attenuation of DNA binding. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
33. Key residues for maintaining architecture, assembly of plant hormone SA receptor NPR1.
- Author
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Ji, Chaoguang, Yang, Wenbo, Wang, Yongan, Su, Chunlin, Li, Xiaorui, Liu, Peiyuan, and Yan, Hanchi
- Subjects
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HORMONE receptors , *SALICYLIC acid , *ZINC ions , *PROTEIN-protein interactions , *PHYTOPATHOGENIC microorganisms - Abstract
Salicylic acid (SA) is a pivotal hormone required for the development of resistance to many pathogens in plants. As an SA receptor, NPR1(Nonexpressor of Pathogenesis-Related Genes 1) plays a key regulatory role in the plant immune response. The function of NPR1 is dependent on the alteration of its oligomer-to-monomer. Research in recent years has proven that NPRs perceive SA and regulate the expression of downstream defense genes, but the mechanism of NPR1 oligomer-to-monomer conversion remains unclear. In this paper, we mainly studied the oligomerization of NPR1. By mutation experiments on some residues in the BTB domain involved in protein interactions, we found that the residue His80 plays a key role in the oligomerization of NPR1. We also found that NPR1, interacting with zinc ions at a ratio close to 1:1, was independent of the residue His80. These findings may help us to understand the conformational conversion of NPR1. •Recombinant NPR1 was oligomerized and binds salicylic acid with a dissociation constant of 1.86 μM. •His80 played an essential role in maintaining the oligomerization of NPR1. •NPR1, interacting with Zinc ions at a ratio closed to 1:1, was independent of the residue His80. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
34. MiR-144 regulates adipogenesis by mediating formation of C/EBPα-FOXO1 protein complex.
- Author
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Lin, Weimin, Wen, Xianyu, Li, Xuexin, Chen, Lei, Wei, Wei, Zhang, Lifan, and Chen, Jie
- Subjects
- *
ADIPOGENESIS , *PROTEINS , *RNA regulation , *GENETIC code , *MICRORNA , *RNA - Abstract
CeRNA effect was an important regulation mode of miRNA mediated bio-activities, however, most of the researches of ceRNA were on ncRNAs synergetic with mRNAs, the exploration of ceRNA effect regulated mRNA interaction was still lack of. Besides, C/EBPα was one of the most crucial adipogenic regulators, which has been demonstrated to form a protein complex with FOXO1 to mediate AdipoQ expression. So that, we try to explore whether the ceRNA effect mediated the interaction of C/EBPα and FOXO1, and identified the key miRNAs of their ceRNA effect. In this paper, we found the ceRNA effect of C/EBPα and FOXO1 mediated their protein complex formation, furthermore regulated its transcriptional role for AdipoQ , thereby influencing pre-adipocytes adipogenesis. More importantly, we demonstrated that the miR-144 was the decisive factor that mediated the ceRNA effect of C/EBPα and FOXO1 to influence AdipoQ , thus regulated pre-adipocytes adipogenesis. This research will provide a new supplementary idea of the miRNA role in mediating coding RNA interaction that regulates pre-adipocyte adipogenesis. • In this research, we first reported the miR-144 mediated the C/EBPα-FOXO1 complex formation by the ceRNA effect. • C/EBPα-FOXO1 protein complex was regulated by miR-144 thus infected its adipogenic role for AdipoQ. • This research was the first study to explore the interaction of the miRNA targeted coding genes by ceRNA effect. • Our report will provide a new supplementary idea of the miRNA role in mediating coding RNA interaction, especially for the adipogenesis. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
35. Oil Red O based method for exosome labelling and detection.
- Author
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Bharati, Shikha, Anjaly, Km, Thoidingjam, Shivani, and Tiku, Ashu Bhan
- Subjects
- *
STAINS & staining (Microscopy) , *EXOSOMES , *CELL anatomy , *MEDICAL sciences - Abstract
With the realization of the role of exosomes in diseases, especially cancer, exosome research is gaining popularity in biomedical sciences. To understand exosome biology, their labelling and tracking studies are important. New and improved methods of exosome labelling for detection and tracking of exosomes need to be developed to harness their therapeutic and diagnostic potential. In this paper, we report a novel, simple and effective method of labelling and detecting exosomes using Oil Red O (ORO), a dye commonly used for lipid staining. Using ORO is a cost effective and easy approach with an intense red coloration of exosomes. Further, the issues faced with commonly used lipophilic dyes for exosome labelling like long-term persistence of dyes, aggregation and micelle formation of dyes, difficulty in distinguishing dye particles from labelled exosomes, and detection of large aggregates of dye or dye-exosome, are also resolved with ORO dye. This method shows good labelling efficacy with very sensitive detection and real-time tracking of the cellular uptake of exosomes. [Display omitted] • A new protocol for exosome staining is established. • Exosome were stained using Oil Red O a commonly used laboratory reagent. • This method shows negligible aggregates with exosomes or dye. • Dye concentration required to stain exosomes does not stain any cell components. • Uptake of the stained exosomes by live cells can be easily detected. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
36. The geometry-dependent regulation of hepatic stellate cells by graphene oxide nanomaterials.
- Author
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Chen, Qi, Huang, Jiabao, Tong, Weizhao, Gui, Xingang, Zheng, Jie, and Hu, Guoxin
- Subjects
- *
GRAPHENE oxide , *LIVER cells , *NANOSTRUCTURED materials , *HEPATIC fibrosis , *QUANTUM dots - Abstract
Nanomaterials are widely used in biomedical applications such as drug delivery, bioimaging, and photothermal therapy. For example, graphene oxide (GO) nanomaterials are among the most popular drug delivery vehicles in treating liver diseases due to their tunable chemical/physical properties, and biocompatibility. However, it has been reported that nanomaterials tend to accumulate in livers. The biophysical impact of the accumulation in liver cells remains unclear, and it may cause the liver fibrosis in the long run. The activation of hepatic stellate cells (HSCs) is one of the key initial steps of liver fibrosis. In this paper, we explored the geometric effect (nanosheets vs. quantum dots) of GO nanomaterials on human HSCs, in terms of cell viability, fibrotic degree, mobility and regulation pathways. Our study showed that GO nanosheets could significantly reduce HSCs cell viability and mobility. The protein expression levels of TGFβRⅡ/Smad2/Smad3 decreased, corresponding to a trend of attenuating fibrotic degree. However, the expression level of α-SMA, a maker protein of fibrosis, increased and contradicted with the projection. Further investigation on mitochondria showed that GO nanosheets disrupted mitochondria membrane and membrane potentials. We found that while modulating fibrotic effect through the TGF-β pathway, GO nanosheets induced oxidative stress and activated HSCs through reactive oxygen species(ROS)pathway. This was confirmed by the decreased expression level of α-SMA after co-incubation of GO nanosheets and n-acetyl cysteine (NAC) with HSCs. GO quantum dots decreased α-SMA expression level at 100 mg/l, along with decrease in GAPDH expression level and constant expression level of β-actin. The correlation between GAPDH and α-SMA remains to be explored. Our study suggested that the biophysical impacts of GO nanomaterials on HSCs are geometry-dependent. Both GO nanosheets and quantum dots can be adapted for attenuating liver fibrosis with further investigation on mechanisms. • The effect of graphene oxide nanomaterials on hepatic stellate cells is geometry-dependent. • Graphene oxide nanosheets triggered TGF-β pathway with disruption of cytoskeleton. • Graphene oxide nanosheets increased oxidative stress by physical interaction with mitochondria. • Graphene oxide nanosheets triggered two counteracting regulation pathways that offset anti-fibrotic effect. • Graphene oxide quantum dots demonstrated anti-fibrotic effect and distinctly decreased GAPDH expression level. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
37. Structure-guided rational design of the Geobacillus thermoglucosidasius feruloyl esterase GthFAE to improve its thermostability.
- Author
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Yang, Wendi, Sun, Lifang, Dong, Panpan, Chen, Yayu, Zhang, Hong, Huang, Xiaojin, Wu, Linjiao, Chen, Leiqing, Jing, Dindin, and Wu, Yunkun
- Subjects
- *
MOLECULAR dynamics , *DYNAMIC simulation , *ESTERASES - Abstract
Feruloyl esterases are indispensable biocatalysts catalyzing the cleavage of ester bonds between polysaccharides and their hydroxycinnamoyl cross-links. GthFAE from Geobacillus thermoglucosidasius was identified as a thermophilic alkaline feruloyl esterase with potential applications in paper manufacturing. To improve the enzymatic properties rationally and efficiently, the structure of GthFAE was solved at 1.9 Å, revealing a core domain of classical α / β hydrolase fold and an inserted α / β cap domain. In silico analysis based on it helped us to investigate whether the residues at the active center have positive effects on the stability, and how. Several site-directed mutations were conducted, of which substitutions at residues T41 and T150 apparently improved the thermostability. The combination mutant T41N/T150R exhibited an optimal temperature of 65 °C, a 6.4 °C higher T m compared to wild type by 80 °C, and a 35-fold longer in half-life (201 min) at 70 °C. Molecular dynamics simulations further illustrated that the structure of T41N/T150R was more stable than the wild type and T150R stabilized the cap domain by introducing salt bridges to the region with E154 and D164. This study not only highlighted residues within the active center on their thermostability improving effects, but also contributed to the prospective industrial application of GthFAE. • The structure of a thermophilic alkaline feruloyl esterase was solved and provided insights into rational design for improving thermostability. • Mutation T41N/T150R at the catalytic pocket greatly improved the thermostability by 80 °C in T m, +6.4 °C to wild type. • The mechanism underlying the improved thermostability was analyzed by molecular dynamic simulations. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
38. A novel carotenoid biosynthetic route via oxidosqualene.
- Author
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Otani, Yusuke, Maoka, Takashi, Kawai-Noma, Shigeko, Saito, Kyoichi, and Umeno, Daisuke
- Subjects
- *
CAROTENOIDS , *DOUBLE bonds , *DESATURASES , *STAPHYLOCOCCUS aureus , *TRITERPENOIDS , *BIOSYNTHESIS - Abstract
Over 800 known carotenoids are synthesized from phytoene or 4,4′-diapophytoene (dehydrosqualene) characterized by three conjugated double bonds. In this paper, we report that carotenoid desaturase CrtN from Staphylococcus aureus and Methylomonas can accept oxidosqualene, which is the precursor for plant- or animal-type triterpenoids, yielding the yellow carotenoid pigments with 8, 9, or 10 conjugated double bonds. The resulting pathway is the second nonnatural route for carotenoid pigments and the first pathway for carotenoid pigments not biosynthesized via (diapo)phytoene. • Some carotenoid desaturases convert oxidosqualene into novel carotenoids. • The biosynthesis of the first acyclic epoxy-dated carotenoid was established. • This is the first pathway for carotenoid pigments that are biosynthesized not via phytoene-type precursors. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
39. Lack of SNF1 induces localization of active Ras in mitochondria and triggers apoptosis in the yeast Saccharomyces cerevisiae.
- Author
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Bonomelli, Barbara, Martegani, Enzo, and Colombo, Sonia
- Subjects
- *
RAS oncogenes , *SACCHAROMYCES cerevisiae , *RAS proteins , *IMMOBILIZED proteins , *CELL death - Abstract
In previous papers we showed that activated Ras proteins are localized to the plasma membrane and in the nucleus in wild-type yeast cells growing exponentially on glucose, while an aberrant accumulation of activated Ras in mitochondria correlated to mitochondrial dysfunction, accumulation of ROS and regulated cell death. Here we show that also in a strain lacking Snf1, the homolog of the AMP-activated protein kinase (AMPK) in Saccharomyces cerevisiae , activated Ras proteins accumulate mainly in these organelles, suggesting an antiapoptotic role for this protein, beside its well-known function in glucose repression. Indeed, in this paper we show that Snf1 protects against apoptosis in Saccharomyces cerevisiae. In particular, following treatment with acetic acid, a well-known inducer of apoptosis in this microorganism, snf1 Δ cells show a significant reduction in cell survival and a higher level of ROS when compared with wild-type cells. More importantly, untreated snf1 Δ cells show a higher percentage of apoptotic cells compared with wild-type cells, which further increases upon treatment with acetic acid. In order to determine whether the role of Snf1 in regulated cell death is dependent on its catalytic activity, we characterized the Snf1-S214E strain, expressing a catalytically inactive form of Snf1. Data on active Ras proteins localization, cell survival, level of ROS and percentage of apoptotic cells are congruent and suggest that the antiapoptotic role of Snf1 is independent on its kinase activity. • Active Ras proteins accumulate mainly in mitochondria in the snf1 Δ strain. • Loss of Snf1 reduces cell survival, while increases ROS level and apoptosis. • The Snf1 protein plays a role as a pro-survival factor in S. cerevisiae. • The antiapoptotic role of Snf1 is independent on its kinase activity. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
40. Is myeloid-derived growth factor a ligand of the sphingosine-1-phosphate receptor 2?
- Author
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Zheng, Yong-Shan, Liu, Ya-Li, Xu, Zeng-Guang, He, Cheng, and Guo, Zhan-Yun
- Subjects
- *
G protein coupled receptors , *SPHINGOSINE-1-phosphate , *CELL membranes - Abstract
Secretory myeloid-derived growth factor (MYDGF) exerts beneficial effects on organ repair, probably via a plasma membrane receptor; however, the identity of the expected receptor has remained elusive. In a recent study, MYDGF was reported as an agonist of the sphingosine-1-phosphate receptor 2 (S1PR2), an A-class G protein-coupled receptor that mediates the functions of the signaling lipid, sphingosine-1-phosphate (S1P). In the present study, we conducted living cell-based functional assays to test whether S1PR2 is a receptor for MYDGF. In the NanoLuc Binary Technology (NanoBiT)-based β-arrestin recruitment assay and the cAMP-response element (CRE)-controlled NanoLuc reporter assay, S1P could efficiently activate human S1PR2 overexpressed in human embryonic kidney (HEK) 293T cells; however, recombinant human MYDGF, overexpressed either from Escherichia coli or HEK293 cells, had no detectable effect. Thus, the results demonstrated that human MYDGF is not a ligand of human S1PR2. Considering the high conservation of MYDGF and S1PR2 in evolution, MYDGF is also probably not a ligand of S1PR2 in other vertebrates. • Secretory MYDGF has beneficial effects on organ repair, but its receptor is unknown. • A recent paper reported that MYDGF is an agonist of the lipid receptor S1PR2. • We tested it via β-arrestin recruitment assay and CRE-controlled reporter assay. • MYDGF had no effects on S1PR2 in these living cell-based functional assays. • It seems that MYDGF is not a ligand of S1PR2 in human and other vertebrates. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
41. Preclinical evaluation of an 18F-labeled Tenascin-C aptamer for PET imaging of atherosclerotic plaque in mouse models of atherosclerosis.
- Author
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Park, Jun Young, Kim, Hyun Jeong, Chae, Ju Ri, Cho, Ye Lim, and Kang, Won Jun
- Subjects
- *
APTAMERS , *POSITRON emission tomography , *ATHEROSCLEROTIC plaque , *STAINS & staining (Microscopy) , *LABORATORY mice , *FOAM cells - Abstract
Tenascin-C is an extracellular matrix glycoprotein strongly expressed in coronary atherosclerotic plaque. Aptamers are single-stranded oligonucleotides that bind to specific target molecules with high affinity. This study hypothesized that tenascin-C expression at atherosclerotic plaque in vivo could be detected by tenascin-C specific aptamers using positron emission tomography (PET). This paper reports the radiosynthesis of a fluorine-18 (18F)-labeled tenascin-C aptamer for the biodistribution and PET imaging of the tenascin-C expression in apolipoprotein E-deficient (ApoE−/−) mice. The aortas ApoE−/− mice showed significantly increased positive areas of Oil red O staining than control C57BL/6 mice, and tenascin-C expression was detected in foam cells accumulated in the subendothelial lesions of ApoE−/− mice. The ex vivo biodistribution of the 18F-labeled tenascin-C aptamer showed significantly increased uptake at the aorta of ApoE−/− mice, and ex vivo autoradiography of aorta revealed the high accumulation of the 18F-labeled tenascin-C aptamer in the atherosclerotic lesions of ApoE−/− mice, which was consistent with the location of the atherosclerotic plaques detected by Oil red O staining. PET imaging of the 18F-labeled tenascin-C aptamer revealed a significantly higher mean standardized uptake in the aorta of the ApoE−/− mice than the control C57BL/6 mice. These data highlight the potential use of tenascin-C aptamer to diagnose atherosclerotic lesions in vivo. • Tenascin-C expressed in the atherosclerotic lesions of aorta obtained from ApoE−/− mice. • Accumulation and retention of 18F-labeled TNC-specific aptamer in the aorta of ApoE−/− mice is higher than that of the control C57BL/6 mice. • Ex vivo autoradiography of 18F-labeled TNC-specific aptamer visualized the atherosclerotic lesions of aorta obtained from ApoE−/− mice. • PET imaging of 18F-labeled TNC-specific aptamer revealed a higher uptake in the aorta of the ApoE−/− mice than the control C57BL/6 mice. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
42. Plasma-induced destruction of Candida albicans cell wall components: A reactive molecular dynamics simulation.
- Author
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Wang, Xiaolong, Pang, Long, Yang, Shuhui, Zou, Liang, Zhang, Yuantao, and Zhao, Tong
- Subjects
- *
MOLECULAR dynamics , *CANDIDA albicans , *REACTIVE oxygen species , *LOW temperature plasmas , *CELL anatomy , *DOUBLE bonds , *BACTERIAL cell walls - Abstract
Cold atmospheric plasma (CAP) has attracted significant attention and has been widely used to inactivate pathogens based on its excellent effect; however, the mechanisms underlying the interactions between plasma-generated species and organisms have not yet been fully elucidated. In this paper, the interactions of reactive oxygen plasma species (O, OH and H 2 O 2) with chitin polymer (the skeletal component of the Candida albicans cell wall) were investigated by means of reactive molecular dynamics simulations from a microscopic point of view. Our simulations show that O and OH species can break important structural bonds (e.g., N–H bonds, O–H bonds and C–H bonds) of chitin. This is followed by a cascade of bond cleavage and double bond formation events. This simulation study aimed to improve the understanding of the micromechanism of plasma-inactivated Candida albicans at the atomic level. • Cold atmospheric plasma can effectively induce the deactivation of candida albicans. • Reactive oxygen species in plasma play a key role in sterilization. • The ground state O atoms and OH radicals do great damage to chitin polymer,and show similarities in the mechanism of important chemical reaction. • Reactive oxygen species can lead to breakage of the β-1,3-glucoside bond. • H 2 O 2 does little damage to chitin polymer and H2O does not react with it. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
43. SARS-Cov-2 spike protein fragment 674–685 protects mitochondria from releasing cytochrome c in response to apoptogenic influence.
- Author
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Kalashnyk, Olena, Lykhmus, Olena, Izmailov, Mykhailo, Koval, Lyudmyla, Komisarenko, Serhiy, and Skok, Maryna
- Subjects
- *
SARS-CoV-2 , *NICOTINIC acetylcholine receptors , *MITOCHONDRIA , *MITOCHONDRIAL proteins , *PROTEINS , *CELL survival , *PLANT mitochondria - Abstract
In spite of numerous studies, many details of SARS-Cov-2 interaction with human cells are still poorly understood. The 674–685 fragment of SARS-Cov-2 spike protein is homologous to the fragment of α-cobratoxin underlying its interaction with α7 nicotinic acetylcholine receptors (nAChRs). The interaction of 674–685 peptide with α7 nAChR has been predicted in silico. In the present paper we confirm this prediction experimentally and investigate the effect of SARS-Cov-2 spike protein peptide on mitochondria, which express α7 nAChRs to regulate apoptosis-related events. We demonstrate that SARS-Cov-2 spike protein peptide 674–685 competes with the antibody against 179–190 fragment of α7 nAChR subunit for the binding to α7-expressing cells and mitochondria and prevents the release of cytochrome c from isolated mitochondria in response to 0.5 mM H 2 O 2 but does not protect intact U373 cells against apoptogenic effect of H 2 O 2. Our data suggest that the α7 nAChR-binding portion of SARS-Cov-2 spike protein prevents mitochondria-driven apoptosis when the virus is uncoated inside the cell and, therefore, supports the infected cell viability before the virus replication cycle is complete. • SARS Cov-2 peptide 674–685 interacts with α7 nAChRs in cells and mitochondria. • SARS peptide displaces α7 nAChRs from α7-Bax complexes in U373 cells. • Binding of SARS peptide to α7 nAChRs attenuates cytochrome c release from isolated mitochondria. • SARS peptide does not protect intact U373 cells from apoptosis. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
44. Increase of Cry 1 expression is a common phenomenon of the disturbed circadian clock in ischemic stroke and opioid addiction.
- Author
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Roy, Kaninika, Maji, Daytee, and Deb, Ishani
- Subjects
- *
OPIOID abuse , *ISCHEMIC stroke , *PHYSIOLOGIC salines , *MOLECULAR clock , *CLOCK genes , *OPIOIDS , *NITROIMIDAZOLES - Abstract
Increasing evidences suggest the involvement of disrupted circadian clock in various pathologies including stroke and substance abuse. Here we took an attempt to do a comparative study on the regulation of circadian clock gene expression under two pathological circumstances - Opioid addiction and Ischemic stroke in the same cell line model (human neuroblastoma SH-SY5Y cells). To mimic in vivo ischemic stroke condition cells were placed in a hypoxia chamber and incubated for 10 h in balanced salt solution lacking glucose, aerated with an anaerobic gas mixture (95% N 2 and 5% C0 2). For opioid addiction cells were treated with morphine sulphate at 10 μM dose for 48 h. We found that although circadian clock gets disturbed in both states, pattern of alteration of clock gene expressions were different and change was more severe in ischemic stroke than addiction. Interestingly, increase in expression of Cry1 showed as a common factor to both the diseases. This paper also emphasizes the interconnection between the severities of neuronal injury induced by ischemic stroke or opioid abuse to circadian system. Finally, this study will further enrich our knowledge towards the pattern of circadian rhythm disturbances under different pathological states. • OGD causes the alterations in the transcript levels of clock components. • The effect of chronic morphine treatment on the clock gene expression is less severe compared to the OGD. • Increase of Cry1 expression is a common factor in OGD and chronic morphine treatment to SH-SY5Y cells. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
45. Small extracellular ring domain is necessary for CD82/KAI1′anti-metastasis function.
- Author
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Ma, Xiaoguang, He, Xin, Wang, Congcong, Huang, Xiaohua, Li, Ying, and Ma, Keli
- Subjects
- *
AMINO acids , *PROLINE , *CELL migration - Abstract
The peptide mimicking small extracellular loop of CD82/KAI1 has been reported to inhibit tumor cell migration and metastasis. This provides an evidence that small extracellular loop domain should be important for the function of CD82/KAI1. In this paper, to investigate the structure basis for the function of EC1 mimic peptide, we systematically analyzed the effects of each amino acid residue in EC1 mimic peptide on its bioactivity. We found that the interfering with the folding of secondary structure with proline, a potent breaker of secondary structure, completely abolished the migration and metastasis-inhibitory activity of EC1 mimic peptide. This means that the bioactivity of EC1 mimic peptide was conformation-dependent. Next, we substitute with proline for amino acid residues in the small extracellular ring region of CD82/KAI1 by the site-specific mutations to disrupting secondary structure and detected its effect on the function of CD82/KAI1. The results showed that the disturbing the secondary structure of small extracellular ring completely abolished the migration and metastasis-inhibitory activity of CD82/KAI1. These results further provide direct evidence that the small extracellular ring is an important function region of CD82/KAI1. • Negatively charged polar amino acids weaken the bioactivity of EC1mimic peptide. • Proline can interfer the folding of second structure of EC1mimic peptide. • The bioactivity of EC1mimic peptide is conformation dependent. • Disturbing the second structure of EC1 abolishes CD82′ anti-metastasis function. • Small extracellular ring domain is necessary for metastasis-suppression role of CD82. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
46. Nonlinear adaptive control of COVID-19 with media campaigns and treatment.
- Author
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Cao, Boqiang and Kang, Ting
- Subjects
- *
COVID-19 , *ADAPTIVE control systems , *COVID-19 pandemic , *COMMUNICABLE diseases - Abstract
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the infection of severe acute respiratory syndrome coronavirus 2, which is spreading all over the world and causing huge human and economic losses. For these reasons, we study the adaptive control problem of COVID-19 in consideration of media campaigns and treatment in this paper. Firstly, a novel compartment model is constructed by analysing the spread mechanism of COVID-19 and a nonlinear adaptive control problem is established. Then, using the estimation of parameters updated by adaptive laws, the controllers are designed to achieve the control goals. Finally, numerical examples are presented to illustrate the control capability to the outbreak of COVID-19. • A COVID-19 model with media campaigns and treatment is established. • The adaptive control problem of COVID-19 model is proposed. • The controllers are designed by using estimated parameters to reach control goals. • The phenomenon of secondary or even multiple outbreaks of COVID-19 is shown. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
47. SARS-CoV-2 spike protein interactions with amyloidogenic proteins: Potential clues to neurodegeneration.
- Author
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Idrees, Danish and Kumar, Vijay
- Subjects
- *
SARS-CoV-2 , *PROTEIN-protein interactions , *CARRIER proteins , *VIRAL proteins , *PROTEIN binding , *HEPARIN - Abstract
The post-infection of COVID-19 includes a myriad of neurologic symptoms including neurodegeneration. Protein aggregation in brain can be considered as one of the important reasons behind the neurodegeneration. SARS-CoV-2 Spike S1 protein receptor binding domain (SARS-CoV-2 S1 RBD) binds to heparin and heparin binding proteins. Moreover, heparin binding accelerates the aggregation of the pathological amyloid proteins present in the brain. In this paper, we have shown that the SARS-CoV-2 S1 RBD binds to a number of aggregation-prone, heparin binding proteins including Aβ, α-synuclein, tau, prion, and TDP-43 RRM. These interactions suggests that the heparin-binding site on the S1 protein might assist the binding of amyloid proteins to the viral surface and thus could initiate aggregation of these proteins and finally leads to neurodegeneration in brain. The results will help us to prevent future outcomes of neurodegeneration by targeting this binding and aggregation process. • SARS-CoV-2 Spike S1 protein receptor binding domain (SARS-CoV-2 S1 RBD) binds to heparin and heparin binding proteins. • Heparin binding accelerates the aggregation of the pathological amyloid proteins present in the brain. • SARS-CoV-2 S1 RBD binds to a number of aggregation-prone, heparin binding proteins including Aβ, α-synuclein, tau, prion, and TDP-43 RRM. • Heparin-binding site on the S1 might assist the binding of amyloid proteins to the viral surface and thus could leads to neurodegeneration in brain. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
48. Crystal structure of SSB complexed with inhibitor myricetin.
- Author
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Huang, Cheng-Yang
- Subjects
- *
CRYSTAL structure , *MYRICETIN , *DNA-binding proteins , *PSEUDOMONAS aeruginosa , *FLAVONOLS , *ANTINEOPLASTIC agents , *ANTI-inflammatory agents - Abstract
Abstract Single-stranded DNA-binding protein (SSB) is essential for all DNA-dependent cellular processes. SSB inhibitors have been recently suggested as broad-spectrum antibacterial agents in antibiotic development. In this paper, we report the first inhibitor-complexed crystal structure of SSB from Pseudomonas aeruginosa PAO1 (PaSSB) at 2.68 Å resolution (PDB entry 5YUN). The inhibitor, myricetin, is a flavonol that possesses many pharmacological activities, such as anticancer, anti-inflammatory, and antibacterial properties, and is beneficial for humans. Four monomers of PaSSB and two of myricetins were found per asymmetric unit. Various interactions between myricetin and PaSSB were examined. Among these, four residues in PaSSB, Lys7, Arg62, Glu80, and Gly107 were found crucial for forming hydrogen bond to myricetin. These two myricetins occupy the grooves for ssDNA-binding of SSB that may prevent ssDNA-wrapping and ssDNA-binding stably from SSB. In addition to explaining how SSB can be inhibited, the myricetin–SSB interaction modes in this paper may also provide insights into how myricetin can bind and inhibit proteins on cancer-signaling pathways. Highlights • The first inhibitor-complexed crystal structure of SSB was determined. • Two SSB-myricetin interaction modes were found. • Lys7, Arg62, Glu80, and Gly107 in PaSSB were found crucial for forming hydrogen bond to myricetin. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
49. Benzyl alcohol inhibits carbonic anhydrases by anchoring to the zinc coordinated water molecule.
- Author
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De Simone, Giuseppina, Bua, Silvia, Supuran, Claudiu T., and Alterio, Vincenzo
- Subjects
- *
BENZYL alcohol , *CARBONIC anhydrase inhibitors , *CARBONIC anhydrase , *BINDING sites , *ZINC - Abstract
Up to date alcohols have been scarcely investigated as carbonic anhydrase (CA) inhibitors. To get more insights into the CA inhibition properties of this class of molecules, in this paper, by means of inhibition assays and X-ray crystallographic studies we report a detailed characterization of the CA inhibition properties and the binding mode to human CA II of benzyl alcohol. Results show that, although possessing a very simple scaffold, this molecule acts as a micromolar CA II inhibitor, which anchors to the enzyme active site by means of an H-bond interaction with the zinc bound solvent molecule. Taken together our results clearly indicate primary alcohols as a class of CA inhibitors that deserve to be more investigated. [Display omitted] • Alcohols have been scarcely investigated as carbonic anhydrase inhibitors (CAIs). • Benzyl alcohol inhibits CAs by anchoring to the zinc-bound water molecule. • Derivatization of benzyl alcohol ring could allow obtaining selective CAIs. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
50. Amuc_1102 from Akkermansia muciniphila adopts an immunoglobulin-like fold related to archaeal type IV pilus.
- Author
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Xiang, Rui, Wang, Junchao, Xu, Wenjuan, Zhang, Min, and Wang, Mingzhu
- Subjects
- *
CRYSTAL structure , *MEMBRANE proteins , *GENE clusters , *INTESTINAL diseases - Abstract
Akkermansia muciniphila is a kind of beneficial microorganism colonized in the human gut. A. muciniphila is closely related to human intestinal health and has a good effect on diseases related to intestinal metabolism. The proteins encoded by the Amuc_1098-Amuc_1102 gene cluster, which are related to the formation and assembly of the pilus, are highly expressed in the membrane protein components of A. muciniphila. In this paper, we report the crystal structure of Amuc_1102 at a resolution of 1.75 Å, which adopts an immunoglobulin (Ig)-like fold. Amuc_1102 shares a similar fold to three archaeal proteins related to type IV pilus (T4P)-like structure, Pilin, FlaF, and FlaG, indicating a similar function. Amuc_1102 exists as a trimer both in the crystal structure and in solution, which differs from the assemblies of Pilin, FlaF, and FlaG. This study provides a structural basis for the elucidation of the T4P formation of A. muciniphila. • We solved the crystal structure of Amuc_1102 from Akkermansia muciniphila. • Amuc_1102 adopts an immunoglobulin-like fold related to archaeal type IV pilus, indicating a similar function. • Amuc_1102 exists as a trimer both in the crystal structure and in solution. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
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