Startseite Discovery of novel potential KIT inhibitors for the treatment of gastrointestinal stromal tumor
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Discovery of novel potential KIT inhibitors for the treatment of gastrointestinal stromal tumor

  • Lili Jiang , Zhongmin Zhang , Zhen Wang und Yong Liu ORCID logo EMAIL logo
Veröffentlicht/Copyright: 3. April 2021
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Open Life Sciences
Aus der Zeitschrift Open Life Sciences Band 16 Heft 1

Abstract

Numerous inhibitors of tyrosine-protein kinase KIT, a receptor tyrosine kinase, have been explored as a viable therapy for the treatment of gastrointestinal stromal tumor (GIST). However, drug resistance due to acquired mutations in KIT makes these drugs almost useless. The present study was designed to screen the novel inhibitors against the activity of the KIT mutants through pharmacophore modeling and molecular docking. The best two pharmacophore models were established using the KIT mutants’ crystal complexes and were used to screen the new compounds with possible KIT inhibitory activity against both activation loop and ATP-binding mutants. As a result, two compounds were identified as potential candidates from the virtual screening, which satisfied the potential binding capabilities, molecular modeling characteristics, and predicted absorption, distribution, metabolism, excretion, toxicity (ADMET) properties. Further molecular docking simulations showed that two compounds made strong hydrogen bond interaction with different KIT mutant proteins. Our results indicated that pharmacophore models based on the receptor–ligand complex had excellent ability to screen KIT inhibitors, and two compounds may have the potential to develop further as the future KIT inhibitors for GIST treatment.

Graphical abstract

Keywords: gastrointestinal stromal tumor; KIT inhibitors; pharmacophore models; molecular docking; ADMET; virtual screening

1 Introduction

Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the gastrointestinal tract. Approximately 85–90% of GISTs are found to harbor activating mutations of KIT or platelet-derived growth factor receptor (PDGFR) [1,2]. These primary activating mutations in GIST generally occur in either KIT juxtamembrane domain (exon 11) or extracellular domain (exon 9) and rarely in the cytoplasmic ATP-binding pocket (exon 13/14) or activation loop (A-loop; exon 17) [3,4,5].

Imatinib, as a first-line therapy drug for GIST patients, has favorable effects for about 86% of KIT primary mutations (Figure S1) [6,7]. However, more than a half of imatinib-treated patients present drug resistance due to the acquired secondary KIT mutations within 2 years [8]. The majority of KIT secondary mutations affects the cytoplasmic ATP-binding pocket (exon 13/14) or A-loop (exon 17) [9]. Sunitinib, an approved second-line therapy drug for imatinib-resistant GIST patients, potently inhibits KIT of ATP-binding pocket mutants to overcome some imatinib-resistant mutants [10]. Unfortunately, sunitinib is ineffective against KIT of A-loop mutants, which accounts for about 50% of imatinib-resistance mutations [6], while ponatinib has been shown to inhibit the variants of KIT through inhibiting exon 11 primary mutants and secondary mutants of the A-loop [11]. Thus, the development of new drugs is needed to overcome resistance mutations in KIT, in particular those in ATP-binding mutants and the A-loop.

Pharmacophore model describes the spatial arrangement between a small active compound and a target protein. It can be used for virtual screening to select novel compounds that match the specified structural requirements of the binding site. The pharmacophore model is generally generated by ligand-based and structure-based methods. In the present study, we approach structure-based pharmacophore modeling, since the crystal structure of KIT protein has been released [12].

In the pursuit of overcoming resistance mutations in KIT, we developed two novel pharmacophore models using the structure-based method. Subsequently, two models were created using the known KIT inhibitors to screen for new compounds that possessed KIT inhibitory activity against both A-loop and ATP-binding pocket mutants. The new compounds were subjected to filter by ADME properties. Molecular docking of the protein–ligand complexes was employed to analyze and evaluate the affinity of the complexes, for revealing the response of protein to the binding of ligands at the atomic level.

2 Materials and methods

2.1 Dataset preparation

We selected 20 structurally diverse compounds with the reported inhibitory activity values from the literature [13,14,15,16,17,18]. The compound selection in training set was deeply considered based on the 3D quantitative structure–activity relationship generation. The respective 2D structure of the compounds with their different activity data used in the training set and test set was represented in the supporting information (Figures S2 and S3). The dataset was used for the pharmacophore validation.

2.2 Pharmacophore models’ generation

The pharmacophore models based on the receptor–ligand complex were built using the complex based pharmacophore (CBP) algorithm of BIOVIA Discovery Studio 2016 (DS 3.0) from two crystal structures of KIT protein. The X-ray crystal structure of complex KIT with inhibitors (PDB ID: 3G0E [7], 4U0I [11]) obtained from the RCSB Protein Data Bank (www.rcsb.org) [19]. The small molecule inhibitors, sunitinib (PDB ID: 3G0E) and ponatinib (PDB ID: 4U0I), were removed from the complexes and moved to a new window as active ligands in building the pharmacophore models. The KIT protein preparation was carried out by removing the water molecules, adding the atoms for optimizing the side-chain conformation of amino acid residues and modeling the missing loop using protein prepare of DS 3.0. Following the aforementioned steps of preparation, the protein was subjected to energy minimization by applying CHARMm minimization. Subsequently, KIT–sunitinib (PDB ID: 3G0E) and KIT–ponatinib (PDB ID: 4U0I), two protein complexes were submitted to the “Receptor–Ligand Pharmacophore Generation module” of DS 3.0 in turn. The features that have been considered for the generation of the pharmacophore models are hydrogen bond acceptor (HBA), hydrogen bond donor (HBD), hydrophobic features (HY), positive ionizable feature (P), and aromatic ring (R).

2.3 Pharmacophore validation

The best pharmacophore model was validated by selectivity scoring which was calculated by a method named “Rules” [20]. The method uses internal rule-based scoring function. The scoring function is based on a genetic function approximation model, which is a function of the feature set in the pharmacophore model and the feature–feature distances of different types of features.

2.4 Pharmacophore-based virtual screening

Small-molecule structures were downloaded from Maybridge database (http://www.maybridge.com/) and Specs database (http://www.specs.net/). These compounds were filtered by Lipinski’s Rule of Five and Veber’s drug-likeness Rules to select the ones with drug-like properties [21,22]. The receiver operating characteristic (ROC) graphs were generated and the quality values, including area under the curve as well as the enrichment factor, were calculated to validate the pharmacophore models. The pharmacophore models could be used for the following screening when their quality values were greater than 0.5. Finally, two well-validated pharmacophore models were employed as a 3D query to screen the rest of the small molecules, about 137,932 compounds.

2.5 ADMET prediction

ADMET means absorption, distribution, metabolism, excretion, and toxicity. The protocol uses the quantitative structure-activity relationship (QSAR) models to estimate a range of ADMET-related properties for small molecules, including aqueous solubility, blood–brain barrier penetration (BBB), cytochrome P450 2D6 inhibition, hepatotoxicity, human intestinal absorption, and plasma protein binding [23]. ADMET prediction can take out the unfit candidates early in the discovery phase, rather than during the more costly drug development phases. In this study, ADMET prediction was done via the program of ADMET Descriptors in DS 3.0.

2.6 Protein homology modeling

Due to the lack of crystal structure, three-dimensional structure of KIT of ATP-binding pocket mutant was performed using homology modeling by an online server of SWISS-MODEL [24]. Briefly, the complete KIT protein sequence was obtained from NCBI (https://www.ncbi.nlm.nih.gov/protein/; Accession number: AAC50969.1). The sequence of KIT was changed according to the mutation forms of the ATP-binding pocket (V654A), which was used for homology modeling by SWISS-MODEL. The template (PDB ID: 3G0E) was manually selected based on the target sequence coverage, experimental resolution, sequence identity, and similarity after sequence alignment. The generated model was selected based on the quality estimation score and the overall structure similarity. The structure refinement of the model was achieved by energy minimization via the OpenMM molecular mechanics library [25]. The quality of the homology-modeled structure of the KIT mutant V654A was evaluated with ERRAT and PROVE programs [26,27]. In addition, the crystal structures of native KIT (PDB ID: 4U0I) and KIT secondary mutants of the A-loop (D816H) (PDB ID: 3G0F [7]) were retrieved from the RCSB Protein Data Bank (http://www1.rcsb.org/).

2.7 Docking computation

Docking is a method to evaluate protein–ligand interactions and binding properties in order to predict the activity of the ligand molecule. In this study, we employed CDOCKER algorithm (Genetic Optimization for Ligand Docking) from BIOVIA Discovery Studio 2016 (DS 3.0), for searching the binding space and ligand conformational space. The docking used in this study was semiflexible in which the receptor proteins were rigid, but the ligands were flexible. In addition, CDOCKER in DS 3.0 used a scoring function, based on the interaction energy between receptor proteins and ligands. The three-dimensional structures of native KIT (PDB ID: 4U0I), D816H mutant KIT (PDB ID: 3G0F), and V654A mutant KIT (Homology modeling) were considered as receptors. In the protein preparation, all the water molecules and complexes bound to receptor molecule were removed, hydrogen atoms were added, and the missing atom residues were built. The binding sites of the proteins were defined based on the active sites from the PDB site records or volume occupied by the known ligand pose already in reports [28,29]. During the docking process, the top 10 ligand binding poses were saved for each ligand according to their CDOCKER energies, and the predicted binding interactions were then analyzed using the standard protocol.

3 Results

3.1 Pharmacophore models’ generation

The pharmacophore hypotheses were generated based on common features (Tables S1 and S2). As shown in Figure 1, Hypo1 and Hypo2 were picked out considering their most chemical features and the highest selectivity scoring. Hypo1, based on the KIT–sunitinib complex, consisted of one HBA, one HBD, and three hydrophobic features (HY1, HY2, and HY3). In Hypo2-based KIT–ponatinib complex three function feature sets were identified, including one HBA, three hydrophobic features (HY1, HY2, and HY3), and two positive ionizable features (P1 and P2). The generated pharmacophore models commonly contained HBA and HY features, which led to a conclusion that these two features are important for the inhibition of KIT activity. In addition, the difference between the two generated pharmacophore models (Hypo1 and Hypo2) was two positive ionizable features, which may be an effect of different KIT mutations. Figure 2, illustrates the geometrical constrains and excluded volume spheres for the features of active compounds with pharmacophore models. Figure S4 further displays the ROC graphs generated by screening the training set. The results indicated that the built pharmacophore models were more sensitive and reliable to screen the novel KIT inhibitors in the following database.

Figure 1 The final pharmacophore model-based KIT–sunitinib and KIT–ponatinib complexes. (a) Pharmacophore model Hypo1 for KIT–sunitinib; (b) pharmacophore model Hypo2 for KIT–ponatinib. The hypothesis features are labeled as follows: hydrogen bond donor (HBD), hydrogen bond acceptor (HBA), hydrophobic feature (HY), and positive ionizable feature (P).
Figure 1

The final pharmacophore model-based KIT–sunitinib and KIT–ponatinib complexes. (a) Pharmacophore model Hypo1 for KIT–sunitinib; (b) pharmacophore model Hypo2 for KIT–ponatinib. The hypothesis features are labeled as follows: hydrogen bond donor (HBD), hydrogen bond acceptor (HBA), hydrophobic feature (HY), and positive ionizable feature (P).

Figure 2 Mapping of each of the best hits to Hypo1 and Hypo2. The colors of the pharmacophore features, HBA, HBD, HY, and P are shown by green sphere, heliotrope sphere, cyan sphere, and red sphere, respectively. (a) Compound 05 is mapped with Hypo1; (b) compound 06 is mapped with Hypo1; (c) compound 05 is mapped with Hypo2; and (d) compound 06 is mapped with Hypo2.
Figure 2

Mapping of each of the best hits to Hypo1 and Hypo2. The colors of the pharmacophore features, HBA, HBD, HY, and P are shown by green sphere, heliotrope sphere, cyan sphere, and red sphere, respectively. (a) Compound 05 is mapped with Hypo1; (b) compound 06 is mapped with Hypo1; (c) compound 05 is mapped with Hypo2; and (d) compound 06 is mapped with Hypo2.

3.2 Pharmacophore-based virtual screening

Two pharmacophore models were employed to screen the database and to test the model specificity. As a result, only dozens of molecules fit all pharmacophore features of Hypo2. Because of the excellent specificity of Hypo2, Hypo1 was employed for the first screening and then Hypo2. After screening, a total of nine compounds were selected from two databases with 137,932 compounds (Figure S5). ADMET computation showed that all nine compounds have excellent ADMET quality except the slightly bad aqueous solubility of three compounds (compound 01, compound 02, and compound 04; Figure 3).

Figure 3 ADMET properties of the screened nine compounds. Abosorption-95 and Abosorption-99 were 95 and 99% confidence of absorption. BBB-95 and BBB-99 were 95 and 99% confidence of BBB. Almost nine compounds had excellent ADMET quality except the slightly bad aqueous solubility of three compounds (compounds 01, 02, and 04 are indicated by arrows).
Figure 3

ADMET properties of the screened nine compounds. Abosorption-95 and Abosorption-99 were 95 and 99% confidence of absorption. BBB-95 and BBB-99 were 95 and 99% confidence of BBB. Almost nine compounds had excellent ADMET quality except the slightly bad aqueous solubility of three compounds (compounds 01, 02, and 04 are indicated by arrows).

3.3 Model building and structure validation

Because no 3D structures for mutant KIT in ATP pocket have been reported in the PDB data bank, the homology modeling was performed to build a 3D structure of the protein [30]. The final 3D structure is shown in Figure S6a. The quality of 3D model was verified by using SWISS-MODEL server and PROCHECK program. Typically, for each residue of the model (Reported on the X-axis), the similarity to the native structure (Y-axis), showing a score above 0.6, was expected to be of high quality (Figure S6b). As shown in Figure S6c, higher QMEAN Z scores indicated better agreement between the model structure and experimental structures of similar size. Scores below −4.0 indicated that model’s quality was very low. The QMEAN Z score of predicted model was −0.18, which indicated the model’s high quality comparable to experimental structures. The Ramachandran plot for the predicted model indicated that 99.7% of residues was in the allowed regions, while only 0.3% was in the disallowed regions, confirming that the predicted model was of high quality (Figure S6d).

3.4 Docking result analysis

Molecule docking can make a relative accurate prediction of the interaction of small molecule with receptor. Many screening research of inhibitor-based protein structure employed mutation proteins built by homology modeling methods to dock with small molecules [31,32]. The receptor–ligand total energy (CDOCKER ENERGY) and the receptor–ligand interactional energy (CDOCKER INTERACTION ENERGY) were the main parameters of CDOCK results, which represented the stability of docking system and the interaction energy in the bonding process of receptor with ligand, respectively.

In the present study, nine compounds, which were selected based on pharmacophore models, were docked with native KIT protein and two mutation proteins. The results (Table 1) showed that all compounds (compounds 01 to 09) have excellent interaction with different proteins (Native KIT, D816H mutant KIT, and V654A mutant KIT) and indicated the high efficiency of pharmacophore models. Moreover, the docking scores were influenced by different mutation types of KIT protein. Finally, to learn more information of the interactions, compounds 05 and 06 were selected to show the 2D diagram interactions, as the potential candidates for inhibition of KIT, based on the docking results and ADMET scores.

Table 1

Docking result of compounds with three protein models

Protein Compound CDOCKER ENERGY (−kcal/mol) CDOCKER INTERACTION ENERGY (−kcal/mol)
Native KIT Compound 01 55.25 54.17
Compound 02 47.52 46.49
Compound 03 31.29 37.69
Compound 04 30.28 51.20
Compound 05 29.49 51.04
Compound 06 28.03 48.68
Compound 07 26.03 46.14
Compound 08 17.56 40.46
Compound 09 15.72 45.00
V654 A mutant KIT Compound 01 57.80 56.87
Compound 02 48.56 48.71
Compound 04 40.14 60.53
Compound 05 32.91 55.95
Compound 07 31.14 52.50
Compound 06 30.74 48.81
Compound 03 28.53 34.54
Compound 08 23.03 45.22
Compound 09 20.16 54.66
D816H mutant KIT Compound 01 57.81 58.91
Compound 02 44.76 51.77
Compound 04 40.14 60.53
Compound 05 32.91 55.95
Compound 06 29.27 47.80
Compound 03 28.53 34.54
Compound 09 20.16 54.66
Compound 07 11.50 37.39
Compound 08 −4.70 32.52

The 2D diagram interactions between compounds 05 and 06, native KIT and two KIT mutants are illustrated clearly in Figure 4. The oxygen atom had strong hydrogen bond interactions with Thr670 residue in D816H, with Glu13 and Gln15 residues in V654A. More over, the benzene and nitrogen-containing heterocyclic rings formed pi-alkyl interactions with Cys809 and Leu644 residues for D816H, Ala93 and Tyr12 residues for V654A, respectively. The binding sites of interactions between compound 05, native KIT, and two KIT mutants were different, including the residues or the major force of interactions. Moreover, compound 06 mainly interacted with D816H and V654A mutant KIT via hydrogen bond interactions and pi-alkyl interactions, but the residues in the binding sites were different from that of compound 05. The diversity of the binding sites may be because of the diversity in the structure of the compounds (compounds 01 to 09) or proteins (native KIT, D816H mutant KIT, and V654A mutant KIT).

Figure 4 The receptor–ligand interactions of screening compounds 05 and 06 with the native KIT protein and two mutation proteins (D816H mutation KIT protein and V654A mutation KIT protein). (a) Interaction of ligands (compounds 05 and 06) with native KIT protein; (b) interaction of ligands (compounds 05 and 06) with D816H mutation KIT protein; and (c) interaction of ligands (compounds 05 and 06) with V654A mutation KIT protein. Compound 05 is red and compound 06 yellow.
Figure 4

The receptor–ligand interactions of screening compounds 05 and 06 with the native KIT protein and two mutation proteins (D816H mutation KIT protein and V654A mutation KIT protein). (a) Interaction of ligands (compounds 05 and 06) with native KIT protein; (b) interaction of ligands (compounds 05 and 06) with D816H mutation KIT protein; and (c) interaction of ligands (compounds 05 and 06) with V654A mutation KIT protein. Compound 05 is red and compound 06 yellow.

4 Discussion

In the past few years, several commercially available KIT inhibitors, for example, imatinib, sunitinib, and ponatinib, are under clinical investigation for GIST treatment. However, many patients are observed to experience rapid disease and present drug resistance after their treatment, which is the most common due to the acquired secondary KIT mutation [33]. The well-recognized mechanisms of acquired secondary KIT mutation include an added ATP-binding domain or the activation-loop domain of KIT [9]. Following these studies, we herein attempted to develop two novel pharmacophore models that could screen the potential candidates for KIT inhibitors with excellent effect in inhibiting two kinds of typical KIT secondary mutants. Previous study of Jiang et al. first established the three-dimensional pharmacophore model of KIT [34]. Almerico et al. also performed a pharmacophore model based on a co-crystallized compound (PDB ID: 1T46 [35]), which was a crystal structure of native KIT kinase [35]. However, their pharmacophore modeling was only used for screening KIT inhibitors without the secondary KIT mutation, which is different from our model. In addition, other studies [36,37] also developed the three-dimensional pharmacophore models of KIT, but the features of the models were different from our models developed in this study. The two pharmacophore models in this study consisted of several features, such as an HBA, an HBD, three hydrophobic features (HY1, HY2, and HY3), and two positive ionizable features (P1 and P2). These features of the pharmacophore models were representative of the characteristic of KIT mutation active site, which could be used for screening the potential candidates. So the pharmacophore models could be used as a fast and reliable tool to filter for discovering novel potential candidates for KIT inhibitor.

In addition, to get further insights into the receptor–ligand interactions between the selected compounds and two kinds of typical KIT secondary mutants, we used the pharmacophore models to screen the database. Finally, two compounds (compounds 5 and 6) were identified as active compounds, which showed excellent ADMET quality and strong interaction with two kinds of typical KIT secondary mutants involving the ATP-binding domain or the activation-loop domain. The interaction sites between compounds (compounds 5 and 6) and different proteins (native KIT, D816H mutant KIT, and V654A mutant KIT) were different, including the residues or the major interaction forces. These differences might be because of the diversity in the structure of compounds or proteins. The docking study was used to reduce false positive and identify the suitable orientation for the ligand in a protein active site as previous studies. For example, Mahadevan et al. used the molecular modeling to explain the impact of KIT mutations on imatinib resistance [38]. Hsueh et al. also introduced molecular modeling to elucidate the interaction between KIT inhibitors and mutant KIT proteins [39]. The molecular modeling showed that nilotinib had the best binding affinity for exon 11/17, which is in consistent with the in vitro inhibitory efficacy study on KIT mutants [39].

5 Conclusion

The resistance mutation in KIT is an important drawback in the clinical treatment of GIST. Hence, it is vital to consider it while exploring the new ways of treating GIST, i.e., by developing compounds that can inhibit the mutant KIT. Sunitinib and ponatinib present excellent effects for inhibiting two kinds of typical KIT secondary mutants. In the present study, the pharmacophore models were generated by using the KIT mutant crystal complexes and were employed to filter the databases. A few efficient compounds were selected. Subsequently, the potential effect was predicted by docking with the models of native KIT and two mutation proteins. The discovery of new KIT inhibitors was researched from the perspective of inhibiting different types of KIT mutants. Finally, two active compounds were identified from the virtual screening which satisfied the pharmacophore models and ADMET properties and also showed strong hydrogen bond interaction with different KIT mutant proteins. Therefore, the in silico screened compounds can be proposed as lead candidates and can be used for further in vitro and in vivo evaluation.

  1. Funding information: This study was financially supported by the National Key Research and Development Program of China (2017YFC1702006) and the Dalian Science and Technology Innovation Foundation (2018J13SN114).

  2. Author contributions: Conceptualization: Yong Liu; data curation: Lili Jiang, Zhongmin Zhang, and Zhen Wang; formal analysis: Lili Jiang, Zhongmin Zhang, and Zhen Wang; funding acquisition: Lili Jiang and Yong Liu; investigation: Lili Jiang, Zhongmin Zhang, and Zhen Wang; methodology: Lili Jiang and Zhongmin Zhang; project administration: Yong Liu; software: Lili Jiang; supervision: Yong Liu; writing – original draft: Lili Jiang; and review and editing: Yong Liu.

  3. Conflict of interest: The authors state no conflict of interest.

  4. Data availability statement: The data sets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2020-09-10
Revised: 2021-01-17
Accepted: 2021-01-27
Published Online: 2021-04-03

© 2021 Lili Jiang et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Artikel in diesem Heft

  1. Biomedical Sciences
  2. Research progress on the mechanism of orexin in pain regulation in different brain regions
  3. Adriamycin-resistant cells are significantly less fit than adriamycin-sensitive cells in cervical cancer
  4. Exogenous spermidine affects polyamine metabolism in the mouse hypothalamus
  5. Iris metastasis of diffuse large B-cell lymphoma misdiagnosed as primary angle-closure glaucoma: A case report and review of the literature
  6. LncRNA PVT1 promotes cervical cancer progression by sponging miR-503 to upregulate ARL2 expression
  7. Two new inflammatory markers related to the CURB-65 score for disease severity in patients with community-acquired pneumonia: The hypersensitive C-reactive protein to albumin ratio and fibrinogen to albumin ratio
  8. Circ_0091579 enhances the malignancy of hepatocellular carcinoma via miR-1287/PDK2 axis
  9. Silencing XIST mitigated lipopolysaccharide (LPS)-induced inflammatory injury in human lung fibroblast WI-38 cells through modulating miR-30b-5p/CCL16 axis and TLR4/NF-κB signaling pathway
  10. Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats
  11. ABCB1 polymorphism in clopidogrel-treated Montenegrin patients
  12. Metabolic profiling of fatty acids in Tripterygium wilfordii multiglucoside- and triptolide-induced liver-injured rats
  13. miR-338-3p inhibits cell growth, invasion, and EMT process in neuroblastoma through targeting MMP-2
  14. Verification of neuroprotective effects of alpha-lipoic acid on chronic neuropathic pain in a chronic constriction injury rat model
  15. Circ_WWC3 overexpression decelerates the progression of osteosarcoma by regulating miR-421/PDE7B axis
  16. Knockdown of TUG1 rescues cardiomyocyte hypertrophy through targeting the miR-497/MEF2C axis
  17. MiR-146b-3p protects against AR42J cell injury in cerulein-induced acute pancreatitis model through targeting Anxa2
  18. miR-299-3p suppresses cell progression and induces apoptosis by downregulating PAX3 in gastric cancer
  19. Diabetes and COVID-19
  20. Discovery of novel potential KIT inhibitors for the treatment of gastrointestinal stromal tumor
  21. TEAD4 is a novel independent predictor of prognosis in LGG patients with IDH mutation
  22. circTLK1 facilitates the proliferation and metastasis of renal cell carcinoma by regulating miR-495-3p/CBL axis
  23. microRNA-9-5p protects liver sinusoidal endothelial cell against oxygen glucose deprivation/reperfusion injury
  24. Long noncoding RNA TUG1 regulates degradation of chondrocyte extracellular matrix via miR-320c/MMP-13 axis in osteoarthritis
  25. Duodenal adenocarcinoma with skin metastasis as initial manifestation: A case report
  26. Effects of Loofah cylindrica extract on learning and memory ability, brain tissue morphology, and immune function of aging mice
  27. Recombinant Bacteroides fragilis enterotoxin-1 (rBFT-1) promotes proliferation of colorectal cancer via CCL3-related molecular pathways
  28. Blocking circ_UBR4 suppressed proliferation, migration, and cell cycle progression of human vascular smooth muscle cells in atherosclerosis
  29. Gene therapy in PIDs, hemoglobin, ocular, neurodegenerative, and hemophilia B disorders
  30. Downregulation of circ_0037655 impedes glioma formation and metastasis via the regulation of miR-1229-3p/ITGB8 axis
  31. Vitamin D deficiency and cardiovascular risk in type 2 diabetes population
  32. Circ_0013359 facilitates the tumorigenicity of melanoma by regulating miR-136-5p/RAB9A axis
  33. Mechanisms of circular RNA circ_0066147 on pancreatic cancer progression
  34. lncRNA myocardial infarction-associated transcript (MIAT) knockdown alleviates LPS-induced chondrocytes inflammatory injury via regulating miR-488-3p/sex determining region Y-related HMG-box 11 (SOX11) axis
  35. Identification of circRNA circ-CSPP1 as a potent driver of colorectal cancer by directly targeting the miR-431/LASP1 axis
  36. Hyperhomocysteinemia exacerbates ischemia-reperfusion injury-induced acute kidney injury by mediating oxidative stress, DNA damage, JNK pathway, and apoptosis
  37. Potential prognostic markers and significant lncRNA–mRNA co-expression pairs in laryngeal squamous cell carcinoma
  38. Gamma irradiation-mediated inactivation of enveloped viruses with conservation of genome integrity: Potential application for SARS-CoV-2 inactivated vaccine development
  39. ADHFE1 is a correlative factor of patient survival in cancer
  40. The association of transcription factor Prox1 with the proliferation, migration, and invasion of lung cancer
  41. Is there a relationship between the prevalence of autoimmune thyroid disease and diabetic kidney disease?
  42. Immunoregulatory function of Dictyophora echinovolvata spore polysaccharides in immunocompromised mice induced by cyclophosphamide
  43. T cell epitopes of SARS-CoV-2 spike protein and conserved surface protein of Plasmodium malariae share sequence homology
  44. Anti-obesity effect and mechanism of mesenchymal stem cells influence on obese mice
  45. Long noncoding RNA HULC contributes to paclitaxel resistance in ovarian cancer via miR-137/ITGB8 axis
  46. Glucocorticoids protect HEI-OC1 cells from tunicamycin-induced cell damage via inhibiting endoplasmic reticulum stress
  47. Prognostic value of the neutrophil-to-lymphocyte ratio in acute organophosphorus pesticide poisoning
  48. Gastroprotective effects of diosgenin against HCl/ethanol-induced gastric mucosal injury through suppression of NF-κβ and myeloperoxidase activities
  49. Silencing of LINC00707 suppresses cell proliferation, migration, and invasion of osteosarcoma cells by modulating miR-338-3p/AHSA1 axis
  50. Successful extracorporeal membrane oxygenation resuscitation of patient with cardiogenic shock induced by phaeochromocytoma crisis mimicking hyperthyroidism: A case report
  51. Effects of miR-185-5p on replication of hepatitis C virus
  52. Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis
  53. Primary localized cutaneous nodular amyloidosis presenting as lymphatic malformation: A case report
  54. Multimodal magnetic resonance imaging analysis in the characteristics of Wilson’s disease: A case report and literature review
  55. Therapeutic potential of anticoagulant therapy in association with cytokine storm inhibition in severe cases of COVID-19: A case report
  56. Neoadjuvant immunotherapy combined with chemotherapy for locally advanced squamous cell lung carcinoma: A case report and literature review
  57. Rufinamide (RUF) suppresses inflammation and maintains the integrity of the blood–brain barrier during kainic acid-induced brain damage
  58. Inhibition of ADAM10 ameliorates doxorubicin-induced cardiac remodeling by suppressing N-cadherin cleavage
  59. Invasive ductal carcinoma and small lymphocytic lymphoma/chronic lymphocytic leukemia manifesting as a collision breast tumor: A case report and literature review
  60. Clonal diversity of the B cell receptor repertoire in patients with coronary in-stent restenosis and type 2 diabetes
  61. CTLA-4 promotes lymphoma progression through tumor stem cell enrichment and immunosuppression
  62. WDR74 promotes proliferation and metastasis in colorectal cancer cells through regulating the Wnt/β-catenin signaling pathway
  63. Down-regulation of IGHG1 enhances Protoporphyrin IX accumulation and inhibits hemin biosynthesis in colorectal cancer by suppressing the MEK-FECH axis
  64. Curcumin suppresses the progression of gastric cancer by regulating circ_0056618/miR-194-5p axis
  65. Scutellarin-induced A549 cell apoptosis depends on activation of the transforming growth factor-β1/smad2/ROS/caspase-3 pathway
  66. lncRNA NEAT1 regulates CYP1A2 and influences steroid-induced necrosis
  67. A two-microRNA signature predicts the progression of male thyroid cancer
  68. Isolation of microglia from retinas of chronic ocular hypertensive rats
  69. Changes of immune cells in patients with hepatocellular carcinoma treated by radiofrequency ablation and hepatectomy, a pilot study
  70. Calcineurin Aβ gene knockdown inhibits transient outward potassium current ion channel remodeling in hypertrophic ventricular myocyte
  71. Aberrant expression of PI3K/AKT signaling is involved in apoptosis resistance of hepatocellular carcinoma
  72. Clinical significance of activated Wnt/β-catenin signaling in apoptosis inhibition of oral cancer
  73. circ_CHFR regulates ox-LDL-mediated cell proliferation, apoptosis, and EndoMT by miR-15a-5p/EGFR axis in human brain microvessel endothelial cells
  74. Resveratrol pretreatment mitigates LPS-induced acute lung injury by regulating conventional dendritic cells’ maturation and function
  75. Ubiquitin-conjugating enzyme E2T promotes tumor stem cell characteristics and migration of cervical cancer cells by regulating the GRP78/FAK pathway
  76. Carriage of HLA-DRB1*11 and 1*12 alleles and risk factors in patients with breast cancer in Burkina Faso
  77. Protective effect of Lactobacillus-containing probiotics on intestinal mucosa of rats experiencing traumatic hemorrhagic shock
  78. Glucocorticoids induce osteonecrosis of the femoral head through the Hippo signaling pathway
  79. Endothelial cell-derived SSAO can increase MLC20 phosphorylation in VSMCs
  80. Downregulation of STOX1 is a novel prognostic biomarker for glioma patients
  81. miR-378a-3p regulates glioma cell chemosensitivity to cisplatin through IGF1R
  82. The molecular mechanisms underlying arecoline-induced cardiac fibrosis in rats
  83. TGF-β1-overexpressing mesenchymal stem cells reciprocally regulate Th17/Treg cells by regulating the expression of IFN-γ
  84. The influence of MTHFR genetic polymorphisms on methotrexate therapy in pediatric acute lymphoblastic leukemia
  85. Red blood cell distribution width-standard deviation but not red blood cell distribution width-coefficient of variation as a potential index for the diagnosis of iron-deficiency anemia in mid-pregnancy women
  86. Small cell neuroendocrine carcinoma expressing alpha fetoprotein in the endometrium
  87. Superoxide dismutase and the sigma1 receptor as key elements of the antioxidant system in human gastrointestinal tract cancers
  88. Molecular characterization and phylogenetic studies of Echinococcus granulosus and Taenia multiceps coenurus cysts in slaughtered sheep in Saudi Arabia
  89. ITGB5 mutation discovered in a Chinese family with blepharophimosis-ptosis-epicanthus inversus syndrome
  90. ACTB and GAPDH appear at multiple SDS-PAGE positions, thus not suitable as reference genes for determining protein loading in techniques like Western blotting
  91. Facilitation of mouse skin-derived precursor growth and yield by optimizing plating density
  92. 3,4-Dihydroxyphenylethanol ameliorates lipopolysaccharide-induced septic cardiac injury in a murine model
  93. Downregulation of PITX2 inhibits the proliferation and migration of liver cancer cells and induces cell apoptosis
  94. Expression of CDK9 in endometrial cancer tissues and its effect on the proliferation of HEC-1B
  95. Novel predictor of the occurrence of DKA in T1DM patients without infection: A combination of neutrophil/lymphocyte ratio and white blood cells
  96. Investigation of molecular regulation mechanism under the pathophysiology of subarachnoid hemorrhage
  97. miR-25-3p protects renal tubular epithelial cells from apoptosis induced by renal IRI by targeting DKK3
  98. Bioengineering and Biotechnology
  99. Green fabrication of Co and Co3O4 nanoparticles and their biomedical applications: A review
  100. Agriculture
  101. Effects of inorganic and organic selenium sources on the growth performance of broilers in China: A meta-analysis
  102. Crop-livestock integration practices, knowledge, and attitudes among smallholder farmers: Hedging against climate change-induced shocks in semi-arid Zimbabwe
  103. Food Science and Nutrition
  104. Effect of food processing on the antioxidant activity of flavones from Polygonatum odoratum (Mill.) Druce
  105. Vitamin D and iodine status was associated with the risk and complication of type 2 diabetes mellitus in China
  106. Diversity of microbiota in Slovak summer ewes’ cheese “Bryndza”
  107. Comparison between voltammetric detection methods for abalone-flavoring liquid
  108. Composition of low-molecular-weight glutenin subunits in common wheat (Triticum aestivum L.) and their effects on the rheological properties of dough
  109. Application of culture, PCR, and PacBio sequencing for determination of microbial composition of milk from subclinical mastitis dairy cows of smallholder farms
  110. Investigating microplastics and potentially toxic elements contamination in canned Tuna, Salmon, and Sardine fishes from Taif markets, KSA
  111. From bench to bar side: Evaluating the red wine storage lesion
  112. Establishment of an iodine model for prevention of iodine-excess-induced thyroid dysfunction in pregnant women
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  114. Characterization of GMPP from Dendrobium huoshanense yielding GDP-D-mannose
  115. Comparative analysis of the SPL gene family in five Rosaceae species: Fragaria vesca, Malus domestica, Prunus persica, Rubus occidentalis, and Pyrus pyrifolia
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  118. Morphological structures and histochemistry of roots and shoots in Myricaria laxiflora (Tamaricaceae)
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  120. In silico analysis of glycosyltransferase 2 family genes in duckweed (Spirodela polyrhiza) and its role in salt stress tolerance
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https://doi.org/10.1515/biol-2021-0036
Schlagwörter für diesen Artikel
gastrointestinal stromal tumor; KIT inhibitors; pharmacophore models; molecular docking; ADMET; virtual screening
Creative Commons
BY 4.0

Artikel in diesem Heft

  1. Biomedical Sciences
  2. Research progress on the mechanism of orexin in pain regulation in different brain regions
  3. Adriamycin-resistant cells are significantly less fit than adriamycin-sensitive cells in cervical cancer
  4. Exogenous spermidine affects polyamine metabolism in the mouse hypothalamus
  5. Iris metastasis of diffuse large B-cell lymphoma misdiagnosed as primary angle-closure glaucoma: A case report and review of the literature
  6. LncRNA PVT1 promotes cervical cancer progression by sponging miR-503 to upregulate ARL2 expression
  7. Two new inflammatory markers related to the CURB-65 score for disease severity in patients with community-acquired pneumonia: The hypersensitive C-reactive protein to albumin ratio and fibrinogen to albumin ratio
  8. Circ_0091579 enhances the malignancy of hepatocellular carcinoma via miR-1287/PDK2 axis
  9. Silencing XIST mitigated lipopolysaccharide (LPS)-induced inflammatory injury in human lung fibroblast WI-38 cells through modulating miR-30b-5p/CCL16 axis and TLR4/NF-κB signaling pathway
  10. Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats
  11. ABCB1 polymorphism in clopidogrel-treated Montenegrin patients
  12. Metabolic profiling of fatty acids in Tripterygium wilfordii multiglucoside- and triptolide-induced liver-injured rats
  13. miR-338-3p inhibits cell growth, invasion, and EMT process in neuroblastoma through targeting MMP-2
  14. Verification of neuroprotective effects of alpha-lipoic acid on chronic neuropathic pain in a chronic constriction injury rat model
  15. Circ_WWC3 overexpression decelerates the progression of osteosarcoma by regulating miR-421/PDE7B axis
  16. Knockdown of TUG1 rescues cardiomyocyte hypertrophy through targeting the miR-497/MEF2C axis
  17. MiR-146b-3p protects against AR42J cell injury in cerulein-induced acute pancreatitis model through targeting Anxa2
  18. miR-299-3p suppresses cell progression and induces apoptosis by downregulating PAX3 in gastric cancer
  19. Diabetes and COVID-19
  20. Discovery of novel potential KIT inhibitors for the treatment of gastrointestinal stromal tumor
  21. TEAD4 is a novel independent predictor of prognosis in LGG patients with IDH mutation
  22. circTLK1 facilitates the proliferation and metastasis of renal cell carcinoma by regulating miR-495-3p/CBL axis
  23. microRNA-9-5p protects liver sinusoidal endothelial cell against oxygen glucose deprivation/reperfusion injury
  24. Long noncoding RNA TUG1 regulates degradation of chondrocyte extracellular matrix via miR-320c/MMP-13 axis in osteoarthritis
  25. Duodenal adenocarcinoma with skin metastasis as initial manifestation: A case report
  26. Effects of Loofah cylindrica extract on learning and memory ability, brain tissue morphology, and immune function of aging mice
  27. Recombinant Bacteroides fragilis enterotoxin-1 (rBFT-1) promotes proliferation of colorectal cancer via CCL3-related molecular pathways
  28. Blocking circ_UBR4 suppressed proliferation, migration, and cell cycle progression of human vascular smooth muscle cells in atherosclerosis
  29. Gene therapy in PIDs, hemoglobin, ocular, neurodegenerative, and hemophilia B disorders
  30. Downregulation of circ_0037655 impedes glioma formation and metastasis via the regulation of miR-1229-3p/ITGB8 axis
  31. Vitamin D deficiency and cardiovascular risk in type 2 diabetes population
  32. Circ_0013359 facilitates the tumorigenicity of melanoma by regulating miR-136-5p/RAB9A axis
  33. Mechanisms of circular RNA circ_0066147 on pancreatic cancer progression
  34. lncRNA myocardial infarction-associated transcript (MIAT) knockdown alleviates LPS-induced chondrocytes inflammatory injury via regulating miR-488-3p/sex determining region Y-related HMG-box 11 (SOX11) axis
  35. Identification of circRNA circ-CSPP1 as a potent driver of colorectal cancer by directly targeting the miR-431/LASP1 axis
  36. Hyperhomocysteinemia exacerbates ischemia-reperfusion injury-induced acute kidney injury by mediating oxidative stress, DNA damage, JNK pathway, and apoptosis
  37. Potential prognostic markers and significant lncRNA–mRNA co-expression pairs in laryngeal squamous cell carcinoma
  38. Gamma irradiation-mediated inactivation of enveloped viruses with conservation of genome integrity: Potential application for SARS-CoV-2 inactivated vaccine development
  39. ADHFE1 is a correlative factor of patient survival in cancer
  40. The association of transcription factor Prox1 with the proliferation, migration, and invasion of lung cancer
  41. Is there a relationship between the prevalence of autoimmune thyroid disease and diabetic kidney disease?
  42. Immunoregulatory function of Dictyophora echinovolvata spore polysaccharides in immunocompromised mice induced by cyclophosphamide
  43. T cell epitopes of SARS-CoV-2 spike protein and conserved surface protein of Plasmodium malariae share sequence homology
  44. Anti-obesity effect and mechanism of mesenchymal stem cells influence on obese mice
  45. Long noncoding RNA HULC contributes to paclitaxel resistance in ovarian cancer via miR-137/ITGB8 axis
  46. Glucocorticoids protect HEI-OC1 cells from tunicamycin-induced cell damage via inhibiting endoplasmic reticulum stress
  47. Prognostic value of the neutrophil-to-lymphocyte ratio in acute organophosphorus pesticide poisoning
  48. Gastroprotective effects of diosgenin against HCl/ethanol-induced gastric mucosal injury through suppression of NF-κβ and myeloperoxidase activities
  49. Silencing of LINC00707 suppresses cell proliferation, migration, and invasion of osteosarcoma cells by modulating miR-338-3p/AHSA1 axis
  50. Successful extracorporeal membrane oxygenation resuscitation of patient with cardiogenic shock induced by phaeochromocytoma crisis mimicking hyperthyroidism: A case report
  51. Effects of miR-185-5p on replication of hepatitis C virus
  52. Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis
  53. Primary localized cutaneous nodular amyloidosis presenting as lymphatic malformation: A case report
  54. Multimodal magnetic resonance imaging analysis in the characteristics of Wilson’s disease: A case report and literature review
  55. Therapeutic potential of anticoagulant therapy in association with cytokine storm inhibition in severe cases of COVID-19: A case report
  56. Neoadjuvant immunotherapy combined with chemotherapy for locally advanced squamous cell lung carcinoma: A case report and literature review
  57. Rufinamide (RUF) suppresses inflammation and maintains the integrity of the blood–brain barrier during kainic acid-induced brain damage
  58. Inhibition of ADAM10 ameliorates doxorubicin-induced cardiac remodeling by suppressing N-cadherin cleavage
  59. Invasive ductal carcinoma and small lymphocytic lymphoma/chronic lymphocytic leukemia manifesting as a collision breast tumor: A case report and literature review
  60. Clonal diversity of the B cell receptor repertoire in patients with coronary in-stent restenosis and type 2 diabetes
  61. CTLA-4 promotes lymphoma progression through tumor stem cell enrichment and immunosuppression
  62. WDR74 promotes proliferation and metastasis in colorectal cancer cells through regulating the Wnt/β-catenin signaling pathway
  63. Down-regulation of IGHG1 enhances Protoporphyrin IX accumulation and inhibits hemin biosynthesis in colorectal cancer by suppressing the MEK-FECH axis
  64. Curcumin suppresses the progression of gastric cancer by regulating circ_0056618/miR-194-5p axis
  65. Scutellarin-induced A549 cell apoptosis depends on activation of the transforming growth factor-β1/smad2/ROS/caspase-3 pathway
  66. lncRNA NEAT1 regulates CYP1A2 and influences steroid-induced necrosis
  67. A two-microRNA signature predicts the progression of male thyroid cancer
  68. Isolation of microglia from retinas of chronic ocular hypertensive rats
  69. Changes of immune cells in patients with hepatocellular carcinoma treated by radiofrequency ablation and hepatectomy, a pilot study
  70. Calcineurin Aβ gene knockdown inhibits transient outward potassium current ion channel remodeling in hypertrophic ventricular myocyte
  71. Aberrant expression of PI3K/AKT signaling is involved in apoptosis resistance of hepatocellular carcinoma
  72. Clinical significance of activated Wnt/β-catenin signaling in apoptosis inhibition of oral cancer
  73. circ_CHFR regulates ox-LDL-mediated cell proliferation, apoptosis, and EndoMT by miR-15a-5p/EGFR axis in human brain microvessel endothelial cells
  74. Resveratrol pretreatment mitigates LPS-induced acute lung injury by regulating conventional dendritic cells’ maturation and function
  75. Ubiquitin-conjugating enzyme E2T promotes tumor stem cell characteristics and migration of cervical cancer cells by regulating the GRP78/FAK pathway
  76. Carriage of HLA-DRB1*11 and 1*12 alleles and risk factors in patients with breast cancer in Burkina Faso
  77. Protective effect of Lactobacillus-containing probiotics on intestinal mucosa of rats experiencing traumatic hemorrhagic shock
  78. Glucocorticoids induce osteonecrosis of the femoral head through the Hippo signaling pathway
  79. Endothelial cell-derived SSAO can increase MLC20 phosphorylation in VSMCs
  80. Downregulation of STOX1 is a novel prognostic biomarker for glioma patients
  81. miR-378a-3p regulates glioma cell chemosensitivity to cisplatin through IGF1R
  82. The molecular mechanisms underlying arecoline-induced cardiac fibrosis in rats
  83. TGF-β1-overexpressing mesenchymal stem cells reciprocally regulate Th17/Treg cells by regulating the expression of IFN-γ
  84. The influence of MTHFR genetic polymorphisms on methotrexate therapy in pediatric acute lymphoblastic leukemia
  85. Red blood cell distribution width-standard deviation but not red blood cell distribution width-coefficient of variation as a potential index for the diagnosis of iron-deficiency anemia in mid-pregnancy women
  86. Small cell neuroendocrine carcinoma expressing alpha fetoprotein in the endometrium
  87. Superoxide dismutase and the sigma1 receptor as key elements of the antioxidant system in human gastrointestinal tract cancers
  88. Molecular characterization and phylogenetic studies of Echinococcus granulosus and Taenia multiceps coenurus cysts in slaughtered sheep in Saudi Arabia
  89. ITGB5 mutation discovered in a Chinese family with blepharophimosis-ptosis-epicanthus inversus syndrome
  90. ACTB and GAPDH appear at multiple SDS-PAGE positions, thus not suitable as reference genes for determining protein loading in techniques like Western blotting
  91. Facilitation of mouse skin-derived precursor growth and yield by optimizing plating density
  92. 3,4-Dihydroxyphenylethanol ameliorates lipopolysaccharide-induced septic cardiac injury in a murine model
  93. Downregulation of PITX2 inhibits the proliferation and migration of liver cancer cells and induces cell apoptosis
  94. Expression of CDK9 in endometrial cancer tissues and its effect on the proliferation of HEC-1B
  95. Novel predictor of the occurrence of DKA in T1DM patients without infection: A combination of neutrophil/lymphocyte ratio and white blood cells
  96. Investigation of molecular regulation mechanism under the pathophysiology of subarachnoid hemorrhage
  97. miR-25-3p protects renal tubular epithelial cells from apoptosis induced by renal IRI by targeting DKK3
  98. Bioengineering and Biotechnology
  99. Green fabrication of Co and Co3O4 nanoparticles and their biomedical applications: A review
  100. Agriculture
  101. Effects of inorganic and organic selenium sources on the growth performance of broilers in China: A meta-analysis
  102. Crop-livestock integration practices, knowledge, and attitudes among smallholder farmers: Hedging against climate change-induced shocks in semi-arid Zimbabwe
  103. Food Science and Nutrition
  104. Effect of food processing on the antioxidant activity of flavones from Polygonatum odoratum (Mill.) Druce
  105. Vitamin D and iodine status was associated with the risk and complication of type 2 diabetes mellitus in China
  106. Diversity of microbiota in Slovak summer ewes’ cheese “Bryndza”
  107. Comparison between voltammetric detection methods for abalone-flavoring liquid
  108. Composition of low-molecular-weight glutenin subunits in common wheat (Triticum aestivum L.) and their effects on the rheological properties of dough
  109. Application of culture, PCR, and PacBio sequencing for determination of microbial composition of milk from subclinical mastitis dairy cows of smallholder farms
  110. Investigating microplastics and potentially toxic elements contamination in canned Tuna, Salmon, and Sardine fishes from Taif markets, KSA
  111. From bench to bar side: Evaluating the red wine storage lesion
  112. Establishment of an iodine model for prevention of iodine-excess-induced thyroid dysfunction in pregnant women
  113. Plant Sciences
  114. Characterization of GMPP from Dendrobium huoshanense yielding GDP-D-mannose
  115. Comparative analysis of the SPL gene family in five Rosaceae species: Fragaria vesca, Malus domestica, Prunus persica, Rubus occidentalis, and Pyrus pyrifolia
  116. Identification of leaf rust resistance genes Lr34 and Lr46 in common wheat (Triticum aestivum L. ssp. aestivum) lines of different origin using multiplex PCR
  117. Investigation of bioactivities of Taxus chinensis, Taxus cuspidata, and Taxus × media by gas chromatography-mass spectrometry
  118. Morphological structures and histochemistry of roots and shoots in Myricaria laxiflora (Tamaricaceae)
  119. Transcriptome analysis of resistance mechanism to potato wart disease
  120. In silico analysis of glycosyltransferase 2 family genes in duckweed (Spirodela polyrhiza) and its role in salt stress tolerance
  121. Comparative study on growth traits and ions regulation of zoysiagrasses under varied salinity treatments
  122. Role of MS1 homolog Ntms1 gene of tobacco infertility
  123. Biological characteristics and fungicide sensitivity of Pyricularia variabilis
  124. In silico/computational analysis of mevalonate pyrophosphate decarboxylase gene families in Campanulids
  125. Identification of novel drought-responsive miRNA regulatory network of drought stress response in common vetch (Vicia sativa)
  126. How photoautotrophy, photomixotrophy, and ventilation affect the stomata and fluorescence emission of pistachios rootstock?
  127. Apoplastic histochemical features of plant root walls that may facilitate ion uptake and retention
  128. Ecology and Environmental Sciences
  129. The impact of sewage sludge on the fungal communities in the rhizosphere and roots of barley and on barley yield
  130. Domestication of wild animals may provide a springboard for rapid variation of coronavirus
  131. Response of benthic invertebrate assemblages to seasonal and habitat condition in the Wewe River, Ashanti region (Ghana)
  132. Molecular record for the first authentication of Isaria cicadae from Vietnam
  133. Twig biomass allocation of Betula platyphylla in different habitats in Wudalianchi Volcano, northeast China
  134. Animal Sciences
  135. Supplementation of probiotics in water beneficial growth performance, carcass traits, immune function, and antioxidant capacity in broiler chickens
  136. Predators of the giant pine scale, Marchalina hellenica (Gennadius 1883; Hemiptera: Marchalinidae), out of its natural range in Turkey
  137. Honey in wound healing: An updated review
  138. NONMMUT140591.1 may serve as a ceRNA to regulate Gata5 in UT-B knockout-induced cardiac conduction block
  139. Radiotherapy for the treatment of pulmonary hydatidosis in sheep
  140. Retraction
  141. Retraction of “Long non-coding RNA TUG1 knockdown hinders the tumorigenesis of multiple myeloma by regulating microRNA-34a-5p/NOTCH1 signaling pathway”
  142. Special Issue on Reuse of Agro-Industrial By-Products
  143. An effect of positional isomerism of benzoic acid derivatives on antibacterial activity against Escherichia coli
  144. Special Issue on Computing and Artificial Techniques for Life Science Applications - Part II
  145. Relationship of Gensini score with retinal vessel diameter and arteriovenous ratio in senile CHD
  146. Effects of different enantiomers of amlodipine on lipid profiles and vasomotor factors in atherosclerotic rabbits
  147. Establishment of the New Zealand white rabbit animal model of fatty keratopathy associated with corneal neovascularization
  148. lncRNA MALAT1/miR-143 axis is a potential biomarker for in-stent restenosis and is involved in the multiplication of vascular smooth muscle cells
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Heruntergeladen am 30.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/biol-2021-0036/html
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