scholarly journals Integrated Analysis and Finding Reveal Anti–Liver Cancer Targets and Mechanisms of Pachyman (Poria cocos Polysaccharides)

2021 ◽  
Vol 12 ◽  
Author(s):  
Li Qin ◽  
Dongning Huang ◽  
Jian Huang ◽  
Fuhui Qin ◽  
Haixin Huang
Keyword(s):  
Molecular Docking ◽  
Experimental Validation ◽  
Molecular Mechanisms ◽  
Clinical Samples ◽  
Integrated Analysis ◽  
Signaling Mechanisms ◽  
Pharmacological Targets ◽  
Anti Cancer ◽  
Bioinformatics Study

This bioinformatics study aimed to characterize and certify crucial anti-cancer targets, functional processes, and molecular mechanisms of Pachyman in treating hepatocellular carcinoma (HCC) by using pharmacology network and molecular docking analyses, by experimental validation. The crucial anti-HCC targets of Pachyman, including ALB, VEGFA, TNF, CASP3, SRC, EGF, CXCR4, STAT3, HRAS, HSP90AA1, MMP9, BCL2L1, FGF2, and PTPRC, were identified. In addition, the correlative networks of all crucial biotargets of Pachyman in treating HCC were created accordingly. Functionally, these crucial genes were correlated using angiogenesis and neoplastic metastasis of HCC. Interestingly, the molecular docking findings indicated that ALB and VEGFA in HCC might be potent pharmacological targets of Pachyman. In experimental validation, the clinical samples of HCC showed reduced ALB protein expression and increased VEGFA protein level. Following Pachyman treatments in vitro, the intracellular level of ALB protein was elevated, whereas the cellular content of VEGFA protein was downregulated. Taken together, current bioinformatics findings based on pharmacology network and molecular docking analyses elucidate the detailed molecular targets and signaling mechanisms of Pachyman in treating HCC. Interestingly, validated biotargets of ALB and VEGFA may be main potential biomarkers for detecting HCC medically.

Novel Findings of Anti-cancer Property of Propofol

2018 ◽  
Vol 18 (2) ◽  
pp. 156-165 ◽  
Author(s):  
Jiaqiang Wang ◽  
Chien-shan Cheng ◽  
Yan Lu ◽  
Xiaowei Ding ◽  
Minmin Zhu ◽  
...  
Keyword(s):  
General Anesthesia ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Intravenous Anesthetic ◽  
The Past ◽  
Anti Cancer ◽  
Underlying Mechanisms ◽  
Recent Attention

Background: Propofol, a widely used intravenous anesthetic agent, is traditionally applied for sedation and general anesthesia. Explanation: Recent attention has been drawn to explore the effect and mechanisms of propofol against cancer progression in vitro and in vivo. Specifically, the proliferation-inhibiting and apoptosis-inducing properties of propofol in cancer have been studied. However, the underlying mechanisms remain unclear. Conclusion: This review focused on the findings within the past ten years and aimed to provide a general overview of propofol's malignance-modulating properties and the potential molecular mechanisms.

scholarly journals Bioinformatic and experimental findings to indicate anti-cancer targets and mechanisms of calycosin against nasopharyngeal carcinoma

2020 ◽  
Author(s):  
Fangxian Liu ◽  
Qijin Pan ◽  
Liangliang Wang ◽  
Shijiang Yi ◽  
Peng Liu ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Molecular Mechanisms ◽  
Apoptotic Cell ◽  
Cell Number ◽  
Network Pharmacology ◽  
Tunel Staining ◽  
Pharmacological Targets ◽  
Experimental Findings

Abstract Background: Calycosin is a naturally-occurring phytoestrogen that reportedly exerts anti- nasopharyngeal carcinoma (NPC) effects. Nevertheless, the molecular mechanisms for anti-NPC using calycosin remain unrevealed. Methods: Thus, a network pharmacology was used to uncover anti-NPC pharmacological targets and mechanisms of calycosin. Additionally, validated experiments were conducted to validate the bioinformatic findings of calycosin for treating NPC. Results: As results, bioinformatic assays showed that the predictive pharmacological targets of calycosin against NPC were TP53, MAPK14, CASP8, MAPK3, CASP3, RIPK1, JUN, ESR1, respectively. And the top 20 biological processes and pharmacological mechanisms of calycosin against NPC were identified accordingly. In clinical data, NPC samples showed positive expression of MAPK14, reduced TP53, CASP8 expressions. In studies in vitro and in vivo, calycosin-dosed NPC cells resulted in reduced cell proliferation, promoted cell apoptosis. In TUNEL staining, calycosin exhibited elevated apoptotic cell number. And immunostaining assays resulted in increased TP53, CASP8 positive cells, and reduced MAPK14 expressions in calycosin-dosed NPC cells and tumor-bearing nude mice. Conclusion: Altogether, these bioinformatic findings reveal optimal pharmacological targets and mechanisms of calycosin against NPC, following with representative identification of human and preclinical experiments. Notably, some of original biotargets may be potentially used to treat NPC.

scholarly journals Anti-Cancer Effects of Green Tea Polyphenols Against Prostate Cancer

Molecules ◽  
2019 ◽  
Vol 24 (1) ◽  
pp. 193 ◽  
Author(s):  
Yasuyoshi Miyata ◽  
Yohei Shida ◽  
Tomoaki Hakariya ◽  
Hideki Sakai
Keyword(s):  
Prostate Cancer ◽  
Green Tea ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Tea Polyphenols ◽  
Green Tea Polyphenols ◽  
Anti Cancer ◽  
Prevention And Treatment

Prostate cancer is the most common cancer among men. Green tea consumption is reported to play an important role in the prevention of carcinogenesis in many types of malignancies, including prostate cancer; however, epidemiological studies show conflicting results regarding these anti-cancer effects. In recent years, in addition to prevention, many investigators have shown the efficacy and safety of green tea polyphenols and combination therapies with green tea extracts and anti-cancer agents in in vivo and in vitro studies. Furthermore, numerous studies have revealed the molecular mechanisms of the anti-cancer effects of green tea extracts. We believe that improved understanding of the detailed pathological roles at the molecular level is important to evaluate the prevention and treatment of prostate cancer. Therefore, in this review, we present current knowledge regarding the anti-cancer effects of green tea extracts in the prevention and treatment of prostate cancer, with a particular focus on the molecular mechanisms of action, such as influencing tumor growth, apoptosis, androgen receptor signaling, cell cycle, and various malignant behaviors. Finally, the future direction for the use of green tea extracts as treatment strategies in patients with prostate cancer is introduced.

scholarly journals Identification of Potential Dipeptidyl Peptidase (DPP)-IV Inhibitors among Moringa oleifera Phytochemicals by Virtual Screening, Molecular Docking Analysis, ADME/T-Based Prediction, and In Vitro Analyses

Molecules ◽  
2020 ◽  
Vol 25 (1) ◽  
pp. 189 ◽  
Author(s):  
Yang Yang ◽  
Chong-Yin Shi ◽  
Jing Xie ◽  
Jia-He Dai ◽  
Shui-Lian He ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Virtual Screening ◽  
Moringa Oleifera ◽  
Molecular Mechanisms ◽  
Dipeptidyl Peptidase ◽  
In Vivo Evaluation ◽  
Docking Analysis ◽  
Dpp Iv ◽  
Molecular Docking Analysis

Moringa oleifera Lam. (MO) is called the “Miracle Tree” because of its extensive pharmacological activity. In addition to being an important food, it has also been used for a long time in traditional medicine in Asia for the treatment of chronic diseases such as diabetes and obesity. In this study, by constructing a library of MO phytochemical structures and using Discovery Studio software, compounds were subjected to virtual screening and molecular docking experiments related to their inhibition of dipeptidyl peptidase (DPP-IV), an important target for the treatment of type 2 diabetes. After the four-step screening process, involving screening for drug-like compounds, predicting the absorption, distribution, metabolism, excretion, and toxicity (ADME/T) of pharmacokinetic properties, LibDock heatmap matching analysis, and CDOCKER molecular docking analysis, three MO components that were candidate DPP-IV inhibitors were identified and their docking modes were analyzed. In vitro activity verification showed that all three MO components had certain DPP-IV inhibitory activities, of which O-Ethyl-4-[(α-l-rhamnosyloxy)-benzyl] carbamate (compound 1) had the highest activity (half-maximal inhibitory concentration [IC50] = 798 nM). This study provides a reference for exploring the molecular mechanisms underlying the anti-diabetic activity of MO. The obtained DPP-IV inhibitors could be used for structural optimization and in-depth in vivo evaluation.

scholarly journals Chemical Profile, Antioxidant and Alpha-Amylase Inhibitory Activity of Leaves Extracts of Annona muricata: A Combined In vitro and In silico Study

2021 ◽  
Vol 11 (2) ◽  
pp. 3470-3479
Keyword(s):  
Molecular Docking ◽  
Inhibitory Activity ◽  
In Silico ◽  
Molecular Mechanisms ◽  
Hydrophobic Interactions ◽  
In Silico Analysis ◽  
Gas Chromatography Mass Spectrometry ◽  
Annona Muricata ◽  
Butanol Extract

Leaves of Annona muricata are commonly used for treating diabetes. This study was conducted to investigate the molecular mechanisms involved in the antidiabetic properties of leaves of Annona muricata. Leaves of Annona muricata were extracted separately with H2O, hydromethanol (50% methanol), methanol, ethylacetate, and n-butanol. Chemical characterization of the extracts was performed by spectrophotometry and Gas chromatography-Mass Spectrometry (GC-MS) techniques. Biological activity was determined by α-amylase inhibition assays and molecular docking. The hydromethanol extract had a total phenolics concentration of 117.00±0.59 µg GAE/mg extract whereas; flavonoids were most abundant in the n-butanol extract accounting for 29.34±8.87 µg QE/mg extract. The n-butanol extract had the best FRAP value of 41.17±0.57 Vit C eqv mM, which was significantly higher than the value of the vitamin C reference. Estimated IC50 for all the extracts did not differ significantly but was significantly higher than the reference compound quercetin. All extracts inhibited α-amylase in vitro albeit significantly lower than acarbose. The hydromethanol extract had the highest inhibitory activity (53.31 ± 0.33%). Furthermore, chemical profiling of the hydromethanol extract revealed the presence of a variety of bioactive compounds. In silico analysis by molecular docking of the compounds identified by GC-MS on α-amylase revealed that the compounds had robust molecular interactions orchestrated by H-bonding and hydrophobic interactions. From the results, it can be concluded that extracts of Annona muricata possess antioxidant phytochemicals that inhibit α-amylase. Therefore, the results justify the use of the plant for the treatment of diabetes.

scholarly journals Prediction of the Molecular Mechanisms Underlying Erlong Zuoci Treatment of Age-Related Hearing Loss via Network Pharmacology-Based Analyses Combined with Experimental Validation

2021 ◽  
Vol 12 ◽  
Author(s):  
Qing Liu ◽  
Ning Li ◽  
Yifang Yang ◽  
Xirui Yan ◽  
Yang Dong ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Experimental Validation ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Synaptic Connections ◽  
Target Proteins ◽  
Age Related ◽  
Age Related Hearing Loss

Background: The traditional Chinese medicine formula ErLong ZuoCi (ELZC) has been extensively used to treat age-related hearing loss (ARHL) in clinical practice in China for centuries. However, the underlying molecular mechanisms are still poorly understood.Objective: Combine network pharmacology with experimental validation to explore the potential molecular mechanisms underlying ELZC with a systematic viewpoint.Methods: The chemical components of ELZC were collected from the Traditional Chinese Medicine System Pharmacology database, and their possible target proteins were predicted using the SwissTargetPrediction database. The putative ARHL-related target proteins were identified from the database: GeneCards and OMIM. We constructed the drug-target network as well as drug-disease specific protein-protein interaction networks and performed clustering and topological property analyses. Functional annotation and signaling pathways were performed by gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. Finally, in vitro experiments were also performed to validate ELZC’s key target proteins and treatment effects on ARHL.Results: In total, 63 chemical compounds from ELZC and 365 putative ARHL-related targets were identified, and 1860 ARHL-related targets were collected from the OMIM and GeneCards. A total of 145 shared targets of ELZC and ARHL were acquired by Venn diagram analysis. Functional enrichment analysis suggested that ELZC might exert its pharmacological effects in multiple biological processes, such as cell proliferation, apoptosis, inflammatory response, and synaptic connections, and the potential targets might be associated with AKT, ERK, and STAT3, as well as other proteins. In vitro experiments revealed that ELZC pretreatment could decrease senescence-associated β-galactosidase activity in hydrogen peroxide-induced auditory hair cells, eliminate DNA damage, and reduce cellular senescence protein p21 and p53. Finally, Western blot analysis confirmed that ELZC could upregulate the predicted target ERK phosphorylation.Conclusion: We provide an integrative network pharmacology approach, in combination with in vitro experiments to explore the underlying molecular mechanisms governing ELZC treatment of ARHL. The protective effects of ELZC against ARHL were predicted to be associated with cellular senescence, inflammatory response, and synaptic connections which might be linked to various pathways such as JNK/STAT3 and ERK cascade signaling pathways. As a prosperous possibility, our experimental data suggest phosphorylation ERK is essential for ELZC to prevent degeneration of cochlear.

scholarly journals Dicer-to-Argonaute switch controls biogenesis of oncogenic miRNA

2021 ◽  
Author(s):  
Francesca M Buffa ◽  
Laura Winchester ◽  
Linda van Bijsterveldt ◽  
Andrew Dhawan
Keyword(s):  
Cancer Progression ◽  
Experimental Validation ◽  
Transcriptional Regulators ◽  
Clinical Samples ◽  
Mirna Biogenesis ◽  
Integrated Analysis ◽  
Biological Processes ◽  
Independent Manner ◽  
Driver Pathway ◽  
Cancer Types

miRNAs are post-transcriptional regulators of gene expression, controlling biological processes from development to pathogenesis. We asked whether the reshaped functional miRNA landscape in cancers is driven by altered transcription of its precursors, or altered biogenesis and maturation of miRNAs. Integrated analysis of genomic and transcriptomic data in 9,111 samples across 10 cancer types and healthy tissues revealed a recurrent genomic switch from DICER-dependent to non-canonical Argonaute-mediated, DICER-independent, miRNA biogenesis. Experimental validation in AGO2-amplified clinical samples and cancer cell lines confirmed that canonical miRNAs can undergo maturation in a DICER-independent manner, and that elevated Argonaute levels promote selective maturation of the oncogenic miR-106b/25 cluster as shown by the altered ratio of mature miRNA to immature pri-miRNA levels. The preferential maturation of these oncogenic miRNAs, whose processing bypasses DICER1, promotes cancer progression and predicts poor prognosis. This highlights the evolution of non-canonical AGO2-dependent oncomiR processing as a novel driver pathway in cancer.

scholarly journals MIR503HG Loss Promotes Endothelial-to-Mesenchymal Transition in Vascular Disease

2021 ◽  
Author(s):  
João P. Monteiro ◽  
Julie Rodor ◽  
Axelle Caudrillier ◽  
Jessica P Scanlon ◽  
Ana-Mishel Spiroski ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Pulmonary Hypertension ◽  
Molecular Mechanisms ◽  
Clinical Samples ◽  
Vascular Remodelling ◽  
Mesenchymal Transition ◽  
Polypyrimidine Tract Binding Protein ◽  
Endothelial To Mesenchymal Transition

Rationale: Endothelial-to-mesenchymal transition (EndMT) is a dynamic biological process involved in pathological vascular remodelling. However, the molecular mechanisms that govern this transition remain largely unknown, including the contribution of long non-coding RNAs (lncRNAs). Objective: To investigate the role of lncRNAs in EndMT and their relevance to vascular remodelling. Methods and Results: To study EndMT in vitro, primary endothelial cells (EC) were treated with transforming growth factor-β2 and interleukin-1β. Single-cell and bulk RNA-sequencing were performed to investigate the transcriptional architecture of EndMT and identify regulated lncRNAs. The functional contribution of seven lncRNAs during EndMT was investigated based on a DsiRNA screening assay. The loss of lncRNA MIR503HG was identified as a common signature across multiple human EC types undergoing EndMT in vitro. MIR503HG depletion induced a spontaneous EndMT phenotype, while its overexpression repressed hallmark EndMT changes, regulating 29% of its transcriptome signature. Importantly, the phenotypic changes induced by MIR503HG were independent of miR-424 and miR-503, which overlap the lncRNA locus. The pathological relevance of MIR503HG down-regulation was confirmed in vivo using Sugen/Hypoxia (SuHx)-induced pulmonary hypertension (PH) in mouse, as well as in human clinical samples, in lung sections and blood outgrowth endothelial cells (BOECs) from pulmonary arterial hypertension (PAH) patients. Overexpression of human MIR503HG in SuHx mice led to reduced mesenchymal marker expression, suggesting MIR503HG therapeutic potential. We also revealed that MIR503HG interacts with the Polypyrimidine Tract Binding Protein 1 (PTB1) and regulates its protein level. PTBP1 regulation of EndMT markers suggests that the role of MIR503HG in EndMT might be mediated in part by PTBP1. Conclusions: This study reports a novel lncRNA transcriptional profile associated with EndMT and reveals the crucial role of the loss of MIR503HG in EndMT and its relevance to pulmonary hypertension.

scholarly journals Bee Venom: From Venom to Drug

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4941
Author(s):  
Abdelwahab Khalil ◽  
Basem H. Elesawy ◽  
Tarek M. Ali ◽  
Osama M. Ahmed
Keyword(s):  
Molecular Mechanisms ◽  
Biological Activities ◽  
Biologically Active ◽  
Bee Venom ◽  
Bee Sting ◽  
Anti Cancer ◽  
Defensive Substance ◽  
Injectable Form

Insects of the order Hymenoptera have a defensive substance that contains many biologically active compounds. Specifically, venom from honeybees (Apis mellifera) contains many enzymes and peptides that are effective against various diseases. Different research papers stated the possibility of using bee venom (a direct bee sting or in an injectable form) in treating several complications; either in vivo or in vitro. Other reports used the active fractions of bee venom clinically or at labratory scale. Many reports and publications have stated that bee venom and its constituents have multiple biological activities including anti-microbial, anti-protozoan, anti-cancer, anti-inflammatory, and anti-arthritic properties. The present review aims to refer to the use of bee venom itself or its fractions in treating several diseases and counteracting drug toxicities as an alternative protocol of therapy. The updated molecular mechanisms of actions of bee venom and its components are discussed in light of the previous updated publications. The review also summarizes the potential of venom loaded on nanoparticles as a drug delivery vehicle and its molecular mechanisms. Finally, the products of bee venom available in markets are also demonstrated.

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