ABSTRACT
Previous studies reported the latex from the fruit of Ficus carica L. (fig) has anti-tumor and antioxidant activities in animal models. However, its active constituents, mechanism of action, and safety remain unknown. The alcohol-precipitated fraction of fig fruit latex (AFFL) was purified and prepared for testing against non-small cell lung cancer (NSCLC). UPLC-TOF-MS/MS was used to examined the components of AFFL. We validated efficacy by researching antitumor phenotypes in vitro and constructing subcutaneous grafts of nude mice with NSCLC, as well as showing the underlying mechanism at the protein level. The results showed that 11 components of AFFL were screened. AFFL significantly inhibited the proliferation, migration, invasion, and clonogenesis of NSCLC cells, promoted cell apoptosis, inhibited tumor growth in A549 xenograft mice, but induced no obvious damage to normal mouse tissues (liver or kidney). Molecular mechanism studies revealed that AFFL could increase Caspase-1 expression in cancer cells by activating the cleavage of Caspase-3 and Caspase-9, inhibiting the activity of Bcl-2, and promoting tumor cell apoptosis. These processes cause gasdermin proteins (GSDMD and GSDME) to be cleaved, releasing N-terminal domain proteins to accumulate and perforate the cell membrane, and promoting tumor cell pyroptosis. In conclusion, our findings suggested that AFFL may promote tumor cell apoptosis and pyroptosis via the Caspase/Gasdermin/AKT signaling pathway and inhibit NSCLC growth in vitro and in vivo, demonstrating that fig latex can be developed as a functional food and drug with anti-NSCLC properties.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Ficus , Lung Neoplasms , Humans , Animals , Mice , Carcinoma, Non-Small-Cell Lung/genetics , Caspases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Latex/metabolism , Gasdermins , Lung Neoplasms/metabolism , Mice, Nude , Tandem Mass Spectrometry , Signal Transduction/physiology , Apoptosis/physiology , Cell Proliferation , Cell Line, TumorABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the pandemic coronavirus disease 2019 (COVID-19), which threatens human health and public safety. In the urgent campaign to develop anti-SARS-CoV-2 therapies, the initial entry step is one of the most appealing targets. In this review, we summarize the current understanding of SARS-CoV-2 cell entry, and the development of targeted antiviral strategies. Moreover, we speculate upon future directions toward next-generation of SARS-CoV-2 entry inhibitors during the upcoming post-pandemic era.
ABSTRACT
Objective:To explore theresearch progress of the computer aided drug discovery for SARS-CoV-2 drugs.Methods:Comprehensively searching internetresour-ces including news report,research papers in scientific journals and academic preprint websites.Results:Since the outbreak of COVID-19, researchers in China and all over the world rapidly start to search drugs for anti-SARS-CoV-2and some progresses were made. This paper reviewed the progress of computer aided discovery of SARS-CoV-2 drugs.Conclusions:Both docking and bioinformatics based methods had achievements and a number of candidate drugs have been identified, but more novel targets should be considered in the future.
ABSTRACT
Objective@#To explore theresearch progress of the computer aided drug discovery for SARS-CoV-2 drugs.@*Methods@#Comprehensively searching internetresour-ces including news report,research papers in scientific journals and academic preprint websites.@*Results@#Since the outbreak of COVID-19, researchers in China and all over the world rapidly start to search drugs for anti-SARS-CoV-2and some progresses were made. This paper reviewed the progress of computer aided discovery of SARS-CoV-2 drugs.@*Conclusions@#Both docking and bioinformatics based methods had achievements and a number of candidate drugs have been identified, but more novel targets should be considered in the future.
ABSTRACT
The mA modification has been implicated as an important epitranscriptomic marker, which plays extensive roles in the regulation of transcript stability, splicing, translation, and localization. Nevertheless, only some genes are repeatedly modified across various conditions and the principle of mA regulation remains elusive. In this study, we performed a systems-level analysis of human genes frequently regulated by mA modification (mAfreq genes) and those occasionally regulated by mA modification (mAocca genes). Compared to the mAocca genes, the mAfreq genes exhibit gene importance-related features, such as lower dN/dS ratio, higher protein-protein interaction network degree, and reduced tissue expression specificity. Signaling network analysis indicates that the mAfreq genes are associated with downstream components of signaling cascades, high-linked signaling adaptors, and specific network motifs like incoherent feed forward loops. Moreover, functional enrichment analysis indicates significant overlaps between the mAfreq genes and genes involved in various layers of gene expression, such as being the microRNA targets and the regulators of RNA processing. Therefore, our findings suggest the potential interplay between mA epitranscriptomic regulation and other gene expression regulatory machineries.
Subject(s)
Humans , Adenosine , Metabolism , Gene Expression Regulation , Gene Regulatory Networks , MicroRNAs , Metabolism , Organ Specificity , Signal TransductionABSTRACT
Sex differences are widely observed under various circumstances ranging from physiological processes to therapeutic responses, and a myriad of sex-biased genes have been identified. In recent years, transcriptomic datasets of microRNAs (miRNAs), an important class of non-coding RNAs, become increasingly accessible. However, comprehensive analysis of sex difference in miRNA expression has not been performed. Here, we identified the differentially-expressed miRNAs between males and females by examining the transcriptomic datasets available in public databases and conducted a systemic analysis of their biological characteristics. Consequently, we identified 73 female-biased miRNAs (FmiRs) and 163 male-biased miRNAs (MmiRs) across four tissues including brain, colorectal mucosa, peripheral blood, and cord blood. Our results suggest that compared to FmiRs, MmiRs tend to be clustered in the human genome and exhibit higher evolutionary rate, higher expression tissue specificity, and lower disease spectrum width. In addition, functional enrichment analysis of miRNAs show that FmiR genes are significantly associated with metabolism process and cell cycle process, whereas MmiR genes tend to be enriched for functions like histone modification and circadian rhythm. In all, the identification and analysis of sex-biased miRNAs together could provide new insights into the biological differences between females and males and facilitate the exploration of sex-biased disease susceptibility and therapy.
Subject(s)
Female , Humans , Male , Biological Evolution , Genome, Human , MicroRNAs , Blood , Genetics , Organ Specificity , Sex Characteristics , TranscriptomeABSTRACT
Various posttranslational modifications (PTMs) participate in nearly all aspects of biological processes by regulating protein functions, and aberrant states of PTMs are frequently implicated in human diseases. Therefore, an integral resource of PTM-disease associations (PDAs) would be a great help for both academic research and clinical use. In this work, we reported PTMD, a well-curated database containing PTMs that are associated with human diseases. We manually collected 1950 known PDAs in 749 proteins for 23 types of PTMs and 275 types of diseases from the literature. Database analyses show that phosphorylation has the largest number of disease associations, whereas neurologic diseases have the largest number of PTM associations. We classified all known PDAs into six classes according to the PTM status in diseases and demonstrated that the upregulation and presence of PTM events account for a predominant proportion of disease-associated PTM events. By reconstructing a disease-gene network, we observed that breast cancers have the largest number of associated PTMs and AKT1 has the largest number of PTMs connected to diseases. Finally, the PTMD database was developed with detailed annotations and can be a useful resource for further analyzing the relations between PTMs and human diseases. PTMD is freely accessible at http://ptmd.biocuckoo.org.
Subject(s)
Humans , Databases, Protein , Disease , Genetics , Gene Regulatory Networks , Phosphorylation , Protein Processing, Post-Translational , Proteins , Metabolism , Search EngineABSTRACT
OBJECTIVE:To study the effects of scorpion’s proteins with different molecular weights on angiogenesis of the transgenic zebrafish. METHODS:The vascular fluorescence transgenic zebrafish models were established. Scorpion’s proteins were separated by ultrafiltration and ion exchange chromatography to obtain the scorpion protein fractions with different molecular weights (3-10 ku,>10-50 ku and>50 ku). The embryos of transgenic zebrafishes were cultured in the above 10,100 and 500 μg/ml scor-pion’s proteins. Intersegmental vessels of the transgenic zebrafishes were counted under the fluorescence microscope to optimize the most suitable scorpion’s protein molecular weight. The vessels were counted again with >50 ku scorpion protein component 1 and 2,so as to select suitable component.RESULTS:The >50 ku scorpion’s protein fraction component 1 with the mass concentration of 500 μg/ml had the highest inhibitory activity for the angiogenesis of the transgenic zebrafish,with inhibitory rate of 92.59%. CONCLUSIONS:Scorpion’s protein and its fractions have the activity of angiogenesis inhibition,which may be one of anti-cancer mechanisms of scorpion.
ABSTRACT
Objective:To predict the microRNAs(miRNAs) related to cardiovascular diseases.Methods: Bioinformatics was used to find all cardiovascular disease related and cardiovascular function related protein-coding genes,and miRNAs were identified that localized the same transcription units as the above genes.Then other cardiovascular disease related miRNAs were identified by an miRNAs set and family analysis and Gene Ontology(GO).Results: Twenty potential cardiovascular disease related miRNAs were predicted from 626 cardiovascular disease related miRNAs,five of which had been confirmed by experiments.Conclusion: This study is of great help for the diagnosis and research of cardiovascular diseases,but the final conclusions need to be confirmed by experiments.
