Editorial

3 pages, 173 KiB

Open AccessEditorial

Molecular World Today and Tomorrow: Recent Trends in Biological Sciences

by Wajid Zaman

Int. J. Mol. Sci. 2024, 25(5), 3068; https://doi.org/10.3390/ijms25053068 - 06 Mar 2024

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Various molecular techniques based on omics (transcriptomics, proteomics, genomics) and phylogenetics have been applied in the field of biological sciences [...] Full article

(This article belongs to the Special Issue Molecular World Today and Tomorrow: Recent Trends in Biological Sciences)

Research

Jump to: Editorial, Review

21 pages, 5436 KiB

Open AccessArticle

Nonspecific Amyloid Aggregation of Chicken Smooth-Muscle Titin: In Vitro Investigations

by Alexander G. Bobylev, Elmira I. Yakupova, Liya G. Bobyleva, Nikolay V. Molochkov, Alexander A. Timchenko, Maria A. Timchenko, Hiroshi Kihara, Alexey D. Nikulin, Azat G. Gabdulkhakov, Tatiana N. Melnik, Nikita V. Penkov, Michail Y. Lobanov, Alexey S. Kazakov, Miklós Kellermayer, Zsolt Mártonfalvi, Oxana V. Galzitskaya and Ivan M. Vikhlyantsev

Int. J. Mol. Sci. 2023, 24(2), 1056; https://doi.org/10.3390/ijms24021056 - 05 Jan 2023

Cited by 4 | Viewed by 1812

Abstract

A giant multidomain protein of striated and smooth vertebrate muscles, titin, consists of tandems of immunoglobulin (Ig)- and fibronectin type III (FnIII)-like domains representing β-sandwiches, as well as of disordered segments. Chicken smooth muscles express several titin isoforms of ~500–1500 kDa. Using various [...] Read more.

A giant multidomain protein of striated and smooth vertebrate muscles, titin, consists of tandems of immunoglobulin (Ig)- and fibronectin type III (FnIII)-like domains representing β-sandwiches, as well as of disordered segments. Chicken smooth muscles express several titin isoforms of ~500–1500 kDa. Using various structural-analysis methods, we investigated in vitro nonspecific amyloid aggregation of the high-molecular-weight isoform of chicken smooth-muscle titin (SMT_HMW, ~1500 kDa). As confirmed by X-ray diffraction analysis, under near-physiological conditions, the protein formed amorphous amyloid aggregates with a quaternary cross-β structure within a relatively short time (~60 min). As shown by circular dichroism and Fourier-transform infrared spectroscopy, the quaternary cross-β structure—unlike other amyloidogenic proteins—formed without changes in the SMT_HMW secondary structure. SMT_HMW aggregates partially disaggregated upon increasing the ionic strength above the physiological level. Based on the data obtained, it is not the complete protein but its particular domains/segments that are likely involved in the formation of intermolecular interactions during SMT_HMW amyloid aggregation. The discovered properties of titin position this protein as an object of interest for studying amyloid aggregation in vitro and expanding our views of the fundamentals of amyloidogenesis. Full article

(This article belongs to the Special Issue Molecular World Today and Tomorrow: Recent Trends in Biological Sciences)

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15 pages, 22412 KiB

Open AccessArticle

Genome-Wide Identification of the SUN Gene Family in Melon (Cucumis melo) and Functional Characterization of Two CmSUN Genes in Regulating Fruit Shape Variation

by Ming Ma, Suya Liu, Zhiwei Wang, Ran Shao, Jianrong Ye, Wei Yan, Hailing Lv, Agula Hasi and Gen Che

Int. J. Mol. Sci. 2022, 23(24), 16047; https://doi.org/10.3390/ijms232416047 - 16 Dec 2022

Cited by 4 | Viewed by 1607

Abstract

Melon (Cucumis melo) is an important economic crop cultivated worldwide. A unique SUN gene family plays a crucial role in regulating plant growth and fruit development, but many SUN family genes and their function have not been well-characterized in melon. In [...] Read more.

Melon (Cucumis melo) is an important economic crop cultivated worldwide. A unique SUN gene family plays a crucial role in regulating plant growth and fruit development, but many SUN family genes and their function have not been well-characterized in melon. In the present study, we performed genome-wide identification and bioinformatics analysis and identified 24 CmSUN family genes that contain integrated and conserved IQ67 domain in the melon genome. Transcriptome data analysis and qRT-PCR results showed that most CmSUNs are specifically enriched in melon reproductive organs, such as young flowers and ovaries. Through genetic transformation in melons, we found that overexpression of CmSUN23-24 and CmSUN25-26-27c led to an increased fruit shape index, suggesting that they act as essential regulators in melon fruit shape variation. Subcellular localization revealed that the CmSUN23-24 protein is located in the cytoplasmic membrane. A direct interaction between CmSUN23-24 and a Calmodulin protein CmCaM5 was found by yeast two-hybrid assay, which indicated their participation in the calcium signal transduction pathway in regulating plant growth. These findings revealed the molecular characteristics, expression profile, and functional pattern of the CmSUN genes, and may provide the theoretical basis for the genetic improvement of melon fruit breeding. Full article

(This article belongs to the Special Issue Molecular World Today and Tomorrow: Recent Trends in Biological Sciences)

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13 pages, 4924 KiB

Open AccessArticle

Screening Key Genes and Biological Pathways in Nasopharyngeal Carcinoma by Integrated Bioinformatics Analysis

by Junhu Tai, Jaehyung Park, Munsoo Han and Tae Hoon Kim

Int. J. Mol. Sci. 2022, 23(24), 15701; https://doi.org/10.3390/ijms232415701 - 11 Dec 2022

Cited by 1 | Viewed by 1582

Abstract

The purpose of this study was to identify the hub genes and biological pathways of nasopharyngeal carcinoma (NPC) through bioinformatics analysis and potential new therapeutic targets. In this study, three datasets were downloaded from the Gene Expression Omnibus (GEO), and differentially expressed genes [...] Read more.

The purpose of this study was to identify the hub genes and biological pathways of nasopharyngeal carcinoma (NPC) through bioinformatics analysis and potential new therapeutic targets. In this study, three datasets were downloaded from the Gene Expression Omnibus (GEO), and differentially expressed genes (DEGs) between NPC and normal tissues were analyzed using the GEO2R online tool. Volcano and heat maps of the DEGs were visualized using the hiplot database. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the upregulated and downregulated DEGs were performed using the DAVID database. Finally, we established a protein-protein interaction (PPI) network using the STRING database and showed the differential expression of hub genes between the normal and tumor tissues. In all, 109,371,221 upregulated DEGs and 139,226,520 downregulated DEGs were obtained in datasets GSE40290, GSE61218, and GSE53819, respectively, and 18 common differential genes, named co-DEGs, were screened in the three datasets. The most abundant biological GO terms of the co-DEGs were inflammatory response et al. The KEGG pathway enrichment analysis showed that co-DEGs mainly participated in the interleukin (IL)-17 signaling pathway et al. Finally, we identified four hub genes using PPI analysis and observed that three of them were highly expressed in tumor tissues. In this study, the hub genes of NPC, such as PTGS2, and pathways such as IL-17 signaling, were identified through bioinformatics analysis, which may be potential new therapeutic targets for NPC. Full article

(This article belongs to the Special Issue Molecular World Today and Tomorrow: Recent Trends in Biological Sciences)

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12 pages, 1107 KiB

Open AccessCommunication

PSSNet—An Accurate Super-Secondary Structure for Protein Segmentation

by Denis V. Petrovsky, Vladimir R. Rudnev, Kirill S. Nikolsky, Liudmila I. Kulikova, Kristina M. Malsagova, Arthur T. Kopylov and Anna L. Kaysheva

Int. J. Mol. Sci. 2022, 23(23), 14813; https://doi.org/10.3390/ijms232314813 - 26 Nov 2022

Cited by 2 | Viewed by 1479

Abstract

A super-secondary structure (SSS) is a spatially unique ensemble of secondary structural elements that determine the three-dimensional shape of a protein and its function, rendering SSSs attractive as folding cores. Understanding known types of SSSs is important for developing a deeper understanding of [...] Read more.

A super-secondary structure (SSS) is a spatially unique ensemble of secondary structural elements that determine the three-dimensional shape of a protein and its function, rendering SSSs attractive as folding cores. Understanding known types of SSSs is important for developing a deeper understanding of the mechanisms of protein folding. Here, we propose a universal PSSNet machine-learning method for SSS recognition and segmentation. For various types of SSS segmentation, this method uses key characteristics of SSS geometry, including the lengths of secondary structural elements and the distances between them, torsion angles, spatial positions of Cα atoms, and primary sequences. Using four types of SSSs (βαβ-unit, α-hairpin, β-hairpin, αα-corner), we showed that extensive SSS sets could be reliably selected from the Protein Data Bank and AlphaFold 2.0 database of protein structures. Full article

(This article belongs to the Special Issue Molecular World Today and Tomorrow: Recent Trends in Biological Sciences)

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11 pages, 15858 KiB

Open AccessArticle

Integrative Analysis of Transcriptome-Wide Association Study and Gene-Based Association Analysis Identifies In Silico Candidate Genes Associated with Juvenile Idiopathic Arthritis

by Shuai Liu, Weiming Gong, Lu Liu, Ran Yan, Shukang Wang and Zhongshang Yuan

Int. J. Mol. Sci. 2022, 23(21), 13555; https://doi.org/10.3390/ijms232113555 - 04 Nov 2022

Cited by 3 | Viewed by 1740

Abstract

Genome-wide association study (GWAS) of Juvenile idiopathic arthritis (JIA) suffers from low power due to limited sample size and the interpretation challenge due to most signals located in non-coding regions. Gene-level analysis could alleviate these issues. Using GWAS summary statistics, we performed two [...] Read more.

Genome-wide association study (GWAS) of Juvenile idiopathic arthritis (JIA) suffers from low power due to limited sample size and the interpretation challenge due to most signals located in non-coding regions. Gene-level analysis could alleviate these issues. Using GWAS summary statistics, we performed two typical gene-level analysis of JIA, transcriptome-wide association studies (TWAS) using FUnctional Summary-based ImputatiON (FUSION) and gene-based analysis using eQTL Multi-marker Analysis of GenoMic Annotation (eMAGMA), followed by comprehensive enrichment analysis. Among 33 overlapped significant genes from these two methods, 11 were previously reported, including TYK2 (P_FUSION = 5.12 × 10⁻⁶, P_eMAGMA = 1.94 × 10⁻⁷ for whole blood), IL-6R (P_FUSION = 8.63 × 10⁻⁷, P_eMAGMA = 2.74 × 10⁻⁶ for cells EBV-transformed lymphocytes), and Fas (P_FUSION = 5.21 × 10⁻⁵, P_eMAGMA = 1.08 × 10⁻⁶ for muscle skeletal). Some newly plausible JIA-associated genes are also reported, including IL-27 (P_FUSION = 2.10 × 10⁻⁷, P_eMAGMA = 3.93 × 10⁻⁸ for Liver), LAT (P_FUSION = 1.53 × 10⁻⁴, P_eMAGMA = 4.62 × 10⁻⁷ for Artery Aorta), and MAGI3 (P_FUSION = 1.30 × 10⁻⁵, P_eMAGMA = 1.73 × 10⁻⁷ for Muscle Skeletal). Enrichment analysis further highlighted 4 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and 10 Gene Ontology (GO) terms. Our findings can benefit the understanding of genetic determinants and potential therapeutic targets for JIA. Full article

(This article belongs to the Special Issue Molecular World Today and Tomorrow: Recent Trends in Biological Sciences)

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14 pages, 6522 KiB

Open AccessArticle

Ferritin Heavy Chain Binds Peroxiredoxin 6 and Inhibits Cell Proliferation and Migration

by Maddalena Di Sanzo, Flora Cozzolino, Anna Martina Battaglia, Ilenia Aversa, Vittoria Monaco, Alessandro Sacco, Flavia Biamonte, Camillo Palmieri, Francesca Procopio, Gianluca Santamaria, Francesco Ortuso, Piero Pucci, Maria Monti and Maria Concetta Faniello

Int. J. Mol. Sci. 2022, 23(21), 12987; https://doi.org/10.3390/ijms232112987 - 26 Oct 2022

Cited by 9 | Viewed by 1703

Abstract

The H Ferritin subunit (FTH1), as well as regulating the homeostasis of intracellular iron, is involved in complex pathways that might promote or inhibit carcinogenesis. This function may be mediated by its ability to interact with different molecules. To gain insight into the [...] Read more.

The H Ferritin subunit (FTH1), as well as regulating the homeostasis of intracellular iron, is involved in complex pathways that might promote or inhibit carcinogenesis. This function may be mediated by its ability to interact with different molecules. To gain insight into the FTH1 interacting molecules, we analyzed its interactome in HEK293T cells. Fifty-one proteins have been identified, and among them, we focused our attention on a member of the peroxiredoxin family (PRDX6), an antioxidant enzyme that plays an important role in cell proliferation and in malignancy development. The FTH1/PRDX6 interaction was further supported by co-immunoprecipitation, in HEK293T and H460 cell lines and by means of computational methods. Next, we demonstrated that FTH1 could inhibit PRDX6-mediated proliferation and migration. Then, the results so far obtained suggested that the interaction between FTH1/PRDX6 in cancer cells might alter cell proliferation and migration, leading to a less invasive phenotype. Full article

(This article belongs to the Special Issue Molecular World Today and Tomorrow: Recent Trends in Biological Sciences)

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14 pages, 2889 KiB

Open AccessArticle

3β-Corner Stability by Comparative Molecular Dynamics Simulations

by Vladimir R. Rudnev, Kirill S. Nikolsky, Denis V. Petrovsky, Liudmila I. Kulikova, Anton M. Kargatov, Kristina A. Malsagova, Alexander A. Stepanov, Arthur T. Kopylov, Anna L. Kaysheva and Alexander V. Efimov

Int. J. Mol. Sci. 2022, 23(19), 11674; https://doi.org/10.3390/ijms231911674 - 02 Oct 2022

Cited by 5 | Viewed by 1333

Abstract

This study explored the mechanisms by which the stability of super-secondary structures of the 3β-corner type autonomously outside the protein globule are maintained in an aqueous environment. A molecular dynamic (MD) study determined the behavioral diversity of a large set of non-homologous 3β-corner [...] Read more.

This study explored the mechanisms by which the stability of super-secondary structures of the 3β-corner type autonomously outside the protein globule are maintained in an aqueous environment. A molecular dynamic (MD) study determined the behavioral diversity of a large set of non-homologous 3β-corner structures of various origins. We focused on geometric parameters such as change in gyration radius, solvent-accessible area, major conformer lifetime and torsion angles, and the number of hydrogen bonds. Ultimately, a set of 3β-corners from 330 structures was characterized by a root mean square deviation (RMSD) of less than 5 Å, a change in the gyration radius of no more than 5%, and the preservation of amino acid residues positioned within the allowed regions on the Ramachandran map. The studied structures retained their topologies throughout the MD experiments. Thus, the 3β-corner structure was found to be rather stable per se in a water environment, i.e., without the rest of a protein molecule, and can act as the nucleus or “ready-made” building block in protein folding. The 3β-corner can also be considered as an independent object for study in field of structural biology. Full article

(This article belongs to the Special Issue Molecular World Today and Tomorrow: Recent Trends in Biological Sciences)

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19 pages, 3191 KiB

Open AccessArticle

Deep-Learning to Predict BRCA Mutation and Survival from Digital H&E Slides of Epithelial Ovarian Cancer

by Camilla Nero, Luca Boldrini, Jacopo Lenkowicz, Maria Teresa Giudice, Alessia Piermattei, Frediano Inzani, Tina Pasciuto, Angelo Minucci, Anna Fagotti, Gianfranco Zannoni, Vincenzo Valentini and Giovanni Scambia

Int. J. Mol. Sci. 2022, 23(19), 11326; https://doi.org/10.3390/ijms231911326 - 26 Sep 2022

Cited by 7 | Viewed by 3269

Abstract

BRCA 1/2 genes mutation status can already determine the therapeutic algorithm of high grade serous ovarian cancer patients. Nevertheless, its assessment is not sufficient to identify all patients with genomic instability, since BRCA 1/2 mutations are only the most well-known mechanisms of homologous [...] Read more.

BRCA 1/2 genes mutation status can already determine the therapeutic algorithm of high grade serous ovarian cancer patients. Nevertheless, its assessment is not sufficient to identify all patients with genomic instability, since BRCA 1/2 mutations are only the most well-known mechanisms of homologous recombination deficiency (HR-d) pathway, and patients displaying HR-d behave similarly to BRCA mutated patients. HRd assessment can be challenging and is progressively overcoming BRCA testing not only for prognostic information but more importantly for drugs prescriptions. However, HR testing is not already integrated in clinical practice, it is quite expensive and it is not refundable in many countries. Selecting patients who are more likely to benefit from this assessment (BRCA 1/2 WT patients) at an early stage of the diagnostic process, would allow an optimization of genomic profiling resources. In this study, we sought to explore whether somatic BRCA1/2 genes status can be predicted using computational pathology from standard hematoxylin and eosin histology. In detail, we adopted a publicly available, deep-learning-based weakly supervised method that uses attention-based learning to automatically identify sub regions of high diagnostic value to accurately classify the whole slide (CLAM). The same model was also tested for progression free survival (PFS) prediction. The model was tested on a cohort of 664 (training set: n = 464, testing set: n = 132) ovarian cancer patients, of whom 233 (35.1%) had a somatic BRCA 1/2 mutation. An area under the curve of 0.7 and 0.55 was achieved in the training and testing set respectively. The model was then further refined by manually identifying areas of interest in half of the cases. 198 images were used for training (126/72) and 87 images for validation (55/32). The model reached a zero classification error on the training set, but the performance was 0.59 in terms of validation ROC AUC, with a 0.57 validation accuracy. Finally, when applied to predict PFS, the model achieved an AUC of 0.71, with a negative predictive value of 0.69, and a positive predictive value of 0.75. Based on these analyses, we have planned further steps of development such as proving a reference classification performance, exploring the hyperparameters space for training optimization, eventually tweaking the learning algorithms and the neural networks architecture for better suiting this specific task. These actions may allow the model to improve performances for all the considered outcomes. Full article

(This article belongs to the Special Issue Molecular World Today and Tomorrow: Recent Trends in Biological Sciences)

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16 pages, 4877 KiB

Open AccessArticle

Target of Rapamycin Regulates Photosynthesis and Cell Growth in Auxenochlorella pyrenoidosa

by Tingting Zhu, Linxuan Li, Huimin Chang, Jiasui Zhan and Maozhi Ren

Int. J. Mol. Sci. 2022, 23(19), 11309; https://doi.org/10.3390/ijms231911309 - 25 Sep 2022

Cited by 3 | Viewed by 1729

Abstract

Auxenochlorella pyrenoidosa is an efficient photosynthetic microalga with autotrophic growth and reproduction, which has the advantages of rich nutrition and high protein content. Target of rapamycin (TOR) is a conserved protein kinase in eukaryotes both structurally and functionally, but little is known about [...] Read more.

Auxenochlorella pyrenoidosa is an efficient photosynthetic microalga with autotrophic growth and reproduction, which has the advantages of rich nutrition and high protein content. Target of rapamycin (TOR) is a conserved protein kinase in eukaryotes both structurally and functionally, but little is known about the TOR signalling in Auxenochlorella pyrenoidosa. Here, we found a conserved ApTOR protein in Auxenochlorella pyrenoidosa, and the key components of TOR complex 1 (TORC1) were present, while the components RICTOR and SIN1 of the TORC2 were absent in Auxenochlorella pyrenoidosa. Drug sensitivity experiments showed that AZD8055 could effectively inhibit the growth of Auxenochlorella pyrenoidosa, whereas rapamycin, Torin1 and KU0063794 had no obvious effect on the growth of Auxenochlorella pyrenoidosaa. Transcriptome data results indicated that Auxenochlorella pyrenoidosa TOR (ApTOR) regulates various intracellular metabolism and signaling pathways in Auxenochlorella pyrenoidosa. Most genes related to chloroplast development and photosynthesis were significantly down-regulated under ApTOR inhibition by AZD8055. In addition, ApTOR was involved in regulating protein synthesis and catabolism by multiple metabolic pathways in Auxenochlorella pyrenoidosa. Importantly, the inhibition of ApTOR by AZD8055 disrupted the normal carbon and nitrogen metabolism, protein and fatty acid metabolism, and TCA cycle of Auxenochlorella pyrenoidosa cells, thus inhibiting the growth of Auxenochlorella pyrenoidosa. These RNA-seq results indicated that ApTOR plays important roles in photosynthesis, intracellular metabolism and cell growth, and provided some insights into the function of ApTOR in Auxenochlorella pyrenoidosa. Full article

(This article belongs to the Special Issue Molecular World Today and Tomorrow: Recent Trends in Biological Sciences)

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12 pages, 3106 KiB

Open AccessArticle

Atomic Simulation of the Binding of JAK1 and JAK2 with the Selective Inhibitor Ruxolitinib

by Maxim Kondratyev, Vladimir R. Rudnev, Kirill S. Nikolsky, Alexander A. Stepanov, Denis V. Petrovsky, Liudmila I. Kulikova, Arthur T. Kopylov, Kristina A. Malsagova and Anna L. Kaysheva

Int. J. Mol. Sci. 2022, 23(18), 10466; https://doi.org/10.3390/ijms231810466 - 09 Sep 2022

Cited by 1 | Viewed by 1674

Abstract

Rheumatoid arthritis belongs to the group of chronic systemic autoimmune diseases characterized by the development of destructive synovitis and extra-articular manifestations. Cytokines regulate a wide range of inflammatory processes involved in the pathogenesis of rheumatoid arthritis and contribute to the induction of autoimmunity [...] Read more.

Rheumatoid arthritis belongs to the group of chronic systemic autoimmune diseases characterized by the development of destructive synovitis and extra-articular manifestations. Cytokines regulate a wide range of inflammatory processes involved in the pathogenesis of rheumatoid arthritis and contribute to the induction of autoimmunity and chronic inflammation. Janus-associated kinase (JAK) and signal transducer and activator of transcription (STAT) proteins mediate cell signaling from cytokine receptors, and are involved in the pathogenesis of autoimmune and inflammatory diseases. Targeted small-molecule drugs that inhibit the functional activity of JAK proteins are used in clinical practice for the treatment of rheumatoid arthritis. In our study, we modeled the interactions of the small-molecule drug ruxolitinib with JAK1 and JAK2 isoforms and determined the binding selectivity using molecular docking. Molecular modeling data show that ruxolitinib selectively binds the JAK1 and JAK2 isoforms with a binding affinity of −8.3 and −8.0 kcal/mol, respectively. The stabilization of ligands in the cavity of kinases occurs primarily through hydrophobic interactions. The amino acid residues of the protein globules of kinases that are responsible for the correct positioning of the drug ruxolitinib and its retention have been determined. Full article

(This article belongs to the Special Issue Molecular World Today and Tomorrow: Recent Trends in Biological Sciences)

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16 pages, 5047 KiB

Open AccessArticle

Aurisin A Complexed with 2,6-Di-O-methyl-β-cyclodextrin Enhances Aqueous Solubility, Thermal Stability, and Antiproliferative Activity against Lung Cancer Cells

by Thanapon Charoenwongpaiboon, Amy Oo, Sutita Nasoontorn, Thanyada Rungrotmongkol, Somdej Kanokmedhakul and Panupong Mahalapbutr

Int. J. Mol. Sci. 2022, 23(17), 9776; https://doi.org/10.3390/ijms23179776 - 29 Aug 2022

Cited by 1 | Viewed by 1803

Abstract

Aurisin A (AA), an aristolane dimer sesquiterpene isolated from the luminescent mushroom Neonothopanus nambi, exhibits various biological and pharmacological effects. However, its poor solubility limits its use for further medicinal applications. This study aimed to improve the water solubility of AA via [...] Read more.

Aurisin A (AA), an aristolane dimer sesquiterpene isolated from the luminescent mushroom Neonothopanus nambi, exhibits various biological and pharmacological effects. However, its poor solubility limits its use for further medicinal applications. This study aimed to improve the water solubility of AA via complexation with β-cyclodextrin (βCD) and its derivatives (2,6-di-O-methyl-βCD (DMβCD) and 2-hydroxypropyl-βCD (HPβCD). A phase solubility analysis demonstrated that the solubility of AA linearly enhanced with increasing concentrations of βCDs (ranked in the order of AA/DMβCD > AA/HPβCD > AA/βCD). Notably, βCDs, especially DMβCD, increased the thermal stability of the inclusion complexes. The thermodynamic study indicated that the complexation between AA and βCD(s) was a spontaneous endothermic reaction, and AA/DMβCD possesses the highest binding strength. The complex formation between AA and DMβCD was confirmed by means of FT-IR, DSC, and SEM. Molecular dynamics simulations revealed that the stability and compactness of the AA/DMβCD complex were higher than those of the DMβCD alone. The encapsulation of AA led to increased intramolecular H-bond formations on the wider rim of DMβCD, enhancing the complex stability. The antiproliferative activity of AA against A549 and H1975 lung cancer cells was significantly improved by complexation with DMβCD. Altogether, the satisfactory water solubility, high thermal stability, and enhanced antitumor potential of the AA/DMβCD inclusion complex would be useful for its application as healthcare products or herbal medicines. Full article

(This article belongs to the Special Issue Molecular World Today and Tomorrow: Recent Trends in Biological Sciences)

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13 pages, 1598 KiB

Open AccessArticle

Exogenously Applied Sodium Nitroprusside Mitigates Lead Toxicity in Rice by Regulating Antioxidants and Metal Stress-Related Transcripts

by Waqas Rahim, Murtaza Khan, Tiba Nazar Ibrahim Al Azzawi, Anjali Pande, Nusrat Jahan Methela, Sajid Ali, Muhammad Imran, Da-Sol Lee, Geun-Mo Lee, Bong-Gyu Mun, Yong-Sun Moon, In-Jung Lee and Byung-Wook Yun

Int. J. Mol. Sci. 2022, 23(17), 9729; https://doi.org/10.3390/ijms23179729 - 27 Aug 2022

Cited by 17 | Viewed by 2074

Abstract

Sustainable agriculture is increasingly being put in danger by environmental contamination with dangerous heavy metals (HMs), especially lead (Pb). Plants have developed a sophisticated mechanism for nitric oxide (NO) production and signaling to regulate hazardous effects of abiotic factors, including HMs. In the [...] Read more.

Sustainable agriculture is increasingly being put in danger by environmental contamination with dangerous heavy metals (HMs), especially lead (Pb). Plants have developed a sophisticated mechanism for nitric oxide (NO) production and signaling to regulate hazardous effects of abiotic factors, including HMs. In the current study, we investigated the role of exogenously applied sodium nitroprusside (SNP, a nitric oxide (NO) donor) in ameliorating the toxic effects of lead (Pb) on rice. For this purpose, plants were subjected to 1.2 mM Pb alone and in combination with 100 µM SNP. We found that under 1.2 mM Pb stress conditions, the accumulation of oxidative stress markers, including hydrogen peroxide (H₂O₂) (37%), superoxide anion (O₂⁻) (28%), malondialdehyde (MDA) (33%), and electrolyte leakage (EL) (34%), was significantly reduced via the application of 100 µM SNP. On the other hand, under the said stress of Pb, the activity of the reactive oxygen species (ROS) scavengers such as polyphenol oxidase (PPO) (60%), peroxidase (POD) (28%), catalase (CAT) (26%), superoxide dismutase (SOD) (42%), and ascorbate peroxidase (APX) (58%) was significantly increased via the application of 100 µM SNP. In addition, the application of 100 µM SNP rescued agronomic traits such as plant height (24%), number of tillers per plant (40%), and visible green pigments (44%) when the plants were exposed to 1.2 mM Pb stress. Furthermore, after exposure to 1.2 mM Pb stress, the expression of the heavy-metal stress-related genes OsPCS1 (44%), OsPCS2 (74%), OsMTP1 (83%), OsMTP5 (53%), OsMT-I-1a (31%), and OsMT-I-1b (24%) was significantly enhanced via the application of 100 µM SNP. Overall, our research evaluates that exogenously applied 100 mM SNP protects rice plants from the oxidative damage brought on by 1.2 mM Pb stress by lowering oxidative stress markers, enhancing the antioxidant system and the transcript accumulation of HMs stress-related genes. Full article

(This article belongs to the Special Issue Molecular World Today and Tomorrow: Recent Trends in Biological Sciences)

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18 pages, 3378 KiB

Open AccessArticle

Toxicity of Bacillus thuringiensis Strains Derived from the Novel Crystal Protein Cry31Aa with High Nematicidal Activity against Rice Parasitic Nematode Aphelenchoides besseyi

by Zhao Liang, Qurban Ali, Yujie Wang, Guangyuan Mu, Xuefei Kan, Yajun Ren, Hakim Manghwar, Qin Gu, Huijun Wu and Xuewen Gao

Int. J. Mol. Sci. 2022, 23(15), 8189; https://doi.org/10.3390/ijms23158189 - 25 Jul 2022

Cited by 14 | Viewed by 2154

Abstract

The plant parasitic nematode, Aphelenchoides besseyi, is a serious pest causing severe damage to various crop plants and vegetables. The Bacillus thuringiensis (Bt) strains, GBAC46 and NMTD81, and the biological strain, FZB42, showed higher nematicidal activity against A. besseyi, by up [...] Read more.

The plant parasitic nematode, Aphelenchoides besseyi, is a serious pest causing severe damage to various crop plants and vegetables. The Bacillus thuringiensis (Bt) strains, GBAC46 and NMTD81, and the biological strain, FZB42, showed higher nematicidal activity against A. besseyi, by up to 88.80, 82.65, and 75.87%, respectively, in a 96-well plate experiment. We screened the whole genomes of the selected strains by protein-nucleic acid alignment. It was found that the Bt strain GBAC46 showed three novel crystal proteins, namely, Cry31Aa, Cry73Aa, and Cry40ORF, which likely provide for the safe control of nematodes. The Cry31Aa protein was composed of 802 amino acids with a molecular weight of 90.257 kDa and contained a conserved delta-endotoxin insecticidal domain. The Cry31Aa exhibited significant nematicidal activity against A. besseyi with a lethal concentration (LC₅₀) value of 131.80 μg/mL. Furthermore, the results of in vitro experiments (i.e., rhodamine and propidium iodide (PI) experiments) revealed that the Cry31Aa protein was taken up by A. besseyi, which caused damage to the nematode’s intestinal cell membrane, indicating that the Cry31Aa produced a pore-formation toxin. In pot experiments, the selected strains GBAC46, NMTD81, and FZB42 significantly reduced the lesions on leaves by up to 33.56%, 45.66, and 30.34% and also enhanced physiological growth parameters such as root length (65.10, 50.65, and 55.60%), shoot length (68.10, 55.60, and 59.45%), and plant fresh weight (60.71, 56.45, and 55.65%), respectively. The number of nematodes obtained from the plants treated with the selected strains (i.e., GBAC46, NMTD81, and FZB42) and A. besseyi was significantly reduced, with 0.56, 0.83., 1.11, and 5.04 seedling mL⁻¹ nematodes were achieved, respectively. Moreover, the qRT-PCR analysis showed that the defense-related genes were upregulated, and the activity of hydrogen peroxide (H₂O₂) increased while malondialdehyde (MDA) decreased in rice leaves compared to the control. Therefore, it was concluded that the Bt strains GBAC46 and NMTD81 can promote rice growth, induce high expression of rice defense-related genes, and activate systemic resistance in rice. More importantly, the application of the novel Cry31Aa protein has high potential for the efficient and safe prevention and green control of plant parasitic nematodes. Full article

(This article belongs to the Special Issue Molecular World Today and Tomorrow: Recent Trends in Biological Sciences)

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16 pages, 924 KiB

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Computational Tactics for Precision Cancer Network Biology

by Heewon Park and Satoru Miyano

Int. J. Mol. Sci. 2022, 23(22), 14398; https://doi.org/10.3390/ijms232214398 - 19 Nov 2022

Cited by 1 | Viewed by 1476

Abstract

Network biology has garnered tremendous attention in understanding complex systems of cancer, because the mechanisms underlying cancer involve the perturbations in the specific function of molecular networks, rather than a disorder of a single gene. In this article, we review the various computational [...] Read more.

Network biology has garnered tremendous attention in understanding complex systems of cancer, because the mechanisms underlying cancer involve the perturbations in the specific function of molecular networks, rather than a disorder of a single gene. In this article, we review the various computational tactics for gene regulatory network analysis, focused especially on personalized anti-cancer therapy. This paper covers three major topics: (1) cell line’s (or patient’s) cancer characteristics specific gene regulatory network estimation, which enables us to reveal molecular interplays under varying conditions of cancer characteristics of cell lines (or patient); (2) computational approaches to interpret the multitudinous and massive networks; (3) network-based application to uncover molecular mechanisms of cancer and related marker identification. We expect that this review will help readers understand personalized computational network biology that plays a significant role in precision cancer medicine. Full article

(This article belongs to the Special Issue Molecular World Today and Tomorrow: Recent Trends in Biological Sciences)

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35 pages, 1654 KiB

Open AccessReview

Developing Genetic Engineering Techniques for Control of Seed Size and Yield

by Intikhab Alam, Khadija Batool, Yuanyuan Huang, Junjie Liu and Liangfa Ge

Int. J. Mol. Sci. 2022, 23(21), 13256; https://doi.org/10.3390/ijms232113256 - 31 Oct 2022

Cited by 8 | Viewed by 2721

Abstract

Many signaling pathways regulate seed size through the development of endosperm and maternal tissues, which ultimately results in a range of variations in seed size or weight. Seed size can be determined through the development of zygotic tissues (endosperm and embryo) and maternal [...] Read more.

Many signaling pathways regulate seed size through the development of endosperm and maternal tissues, which ultimately results in a range of variations in seed size or weight. Seed size can be determined through the development of zygotic tissues (endosperm and embryo) and maternal ovules. In addition, in some species such as rice, seed size is largely determined by husk growth. Transcription regulator factors are responsible for enhancing cell growth in the maternal ovule, resulting in seed growth. Phytohormones induce significant effects on entire features of growth and development of plants and also regulate seed size. Moreover, the vegetative parts are the major source of nutrients, including the majority of carbon and nitrogen-containing molecules for the reproductive part to control seed size. There is a need to increase the size of seeds without affecting the number of seeds in plants through conventional breeding programs to improve grain yield. In the past decades, many important genetic factors affecting seed size and yield have been identified and studied. These important factors constitute dynamic regulatory networks governing the seed size in response to environmental stimuli. In this review, we summarized recent advances regarding the molecular factors regulating seed size in Arabidopsis and other crops, followed by discussions on strategies to comprehend crops’ genetic and molecular aspects in balancing seed size and yield. Full article

(This article belongs to the Special Issue Molecular World Today and Tomorrow: Recent Trends in Biological Sciences)

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16 pages, 1512 KiB

Open AccessReview

Vaccine for Diabetes—Where Do We Stand?

by Dinesh Kumar Chellappan, Richie R. Bhandare, Afzal B. Shaik, Krishna Prasad, Nurfatihah Azlyna Ahmad Suhaimi, Wei Sheng Yap, Arpita Das, Pradipta Banerjee, Nandini Ghosh, Tanner Guith, Amitava Das, Sarannya Balakrishnan, Mayuren Candasamy, Jayashree Mayuren, Kishneth Palaniveloo, Gaurav Gupta, Sachin Kumar Singh and Kamal Dua

Int. J. Mol. Sci. 2022, 23(16), 9470; https://doi.org/10.3390/ijms23169470 - 22 Aug 2022

Cited by 2 | Viewed by 4559

Abstract

Diabetes is an endocrinological disorder with a rapidly increasing number of patients globally. Over the last few years, the alarming status of diabetes has become a pivotal factor pertaining to morbidity and mortality among the youth as well as middle-aged people. Current developments [...] Read more.

Diabetes is an endocrinological disorder with a rapidly increasing number of patients globally. Over the last few years, the alarming status of diabetes has become a pivotal factor pertaining to morbidity and mortality among the youth as well as middle-aged people. Current developments in our understanding related to autoimmune responses leading to diabetes have developed a cause for concern in the prospective usage of immunomodulatory agents to prevent diabetes. The mechanism of action of vaccines varies greatly, such as removing autoreactive T cells and inhibiting the interactions between immune cells. Currently, most developed diabetes vaccines have been tested in animal models, while only a few human trials have been completed with positive outcomes. In this review, we investigate the undergoing clinical trial studies for the development of a prototype diabetes vaccine. Full article

(This article belongs to the Special Issue Molecular World Today and Tomorrow: Recent Trends in Biological Sciences)

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15 pages, 1668 KiB

Open AccessReview

Degradation Mechanism of Autophagy-Related Proteins and Research Progress

by Yanhui Zhou, Hakim Manghwar, Weiming Hu and Fen Liu

Int. J. Mol. Sci. 2022, 23(13), 7301; https://doi.org/10.3390/ijms23137301 - 30 Jun 2022

Cited by 10 | Viewed by 3184

Abstract

In all eukaryotes, autophagy is the main pathway for nutrient recycling, which encapsulates parts of the cytoplasm and organelles in double-membrane vesicles, and then fuses with lysosomes/vacuoles to degrade them. Autophagy is a highly dynamic and relatively complex process influenced by multiple factors. [...] Read more.

In all eukaryotes, autophagy is the main pathway for nutrient recycling, which encapsulates parts of the cytoplasm and organelles in double-membrane vesicles, and then fuses with lysosomes/vacuoles to degrade them. Autophagy is a highly dynamic and relatively complex process influenced by multiple factors. Under normal growth conditions, it is maintained at basal levels. However, when plants are subjected to biotic and abiotic stresses, such as pathogens, drought, waterlogging, nutrient deficiencies, etc., autophagy is activated to help cells to survive under stress conditions. At present, the regulation of autophagy is mainly reflected in hormones, second messengers, post-transcriptional regulation, and protein post-translational modification. In recent years, the degradation mechanism of autophagy-related proteins has attracted much attention. In this review, we have summarized how autophagy-related proteins are degraded in yeast, animals, and plants, which will help us to have a more comprehensive and systematic understanding of the regulation mechanisms of autophagy. Moreover, research progress on the degradation of autophagy-related proteins in plants has been discussed. Full article

(This article belongs to the Special Issue Molecular World Today and Tomorrow: Recent Trends in Biological Sciences)

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