scholarly journals Metabolomics Tools Assisting Classic Screening Methods in Discovering New Antibiotics from Mangrove Actinomycetia in Leizhou Peninsula

Marine Drugs ◽  
2021 ◽  
Vol 19 (12) ◽  
pp. 688
Author(s):  
Qin-Pei Lu ◽  
Yong-Mei Huang ◽  
Shao-Wei Liu ◽  
Gang Wu ◽  
Qin Yang ◽  
...  
Keyword(s):  
Fermentation Broth ◽  
Early Stage ◽  
Selection Process ◽  
Scale Up ◽  
Antibacterial Activities ◽  
Biologically Active ◽  
Screening Methods ◽  
Mangrove Soil ◽  
Rich Diversity ◽  
Antibiotic Discovery

Mangrove actinomycetia are considered one of the promising sources for discovering novel biologically active compounds. Traditional bioactivity- and/or taxonomy-based methods are inefficient and usually result in the re-discovery of known metabolites. Thus, improving selection efficiency among strain candidates is of interest especially in the early stage of the antibiotic discovery program. In this study, an integrated strategy of combining phylogenetic data and bioactivity tests with a metabolomics-based dereplication approach was applied to fast track the selection process. A total of 521 actinomycetial strains affiliated to 40 genera in 23 families were isolated from 13 different mangrove soil samples by the culture-dependent method. A total of 179 strains affiliated to 40 different genera with a unique colony morphology were selected to evaluate antibacterial activity against 12 indicator bacteria. Of the 179 tested isolates, 47 showed activities against at least one of the tested pathogens. Analysis of 23 out of 47 active isolates using UPLC-HRMS-PCA revealed six outliers. Further analysis using the OPLS-DA model identified five compounds from two outliers contributing to the bioactivity against drug-sensitive A. baumannii. Molecular networking was used to determine the relationship of significant metabolites in six outliers and to find their potentially new congeners. Finally, two Streptomyces strains (M22, H37) producing potentially new compounds were rapidly prioritized on the basis of their distinct chemistry profiles, dereplication results, and antibacterial activities, as well as taxonomical information. Two new trioxacarcins with keto-reduced trioxacarcinose B, gutingimycin B (16) and trioxacarcin G (20), together with known gutingimycin (12), were isolated from the scale-up fermentation broth of Streptomyces sp. M22. Our study demonstrated that metabolomics tools could greatly assist classic antibiotic discovery methods in strain prioritization to improve efficiency in discovering novel antibiotics from those highly productive and rich diversity ecosystems.

scholarly journals Exploitation of Potentially New Antibiotics from Mangrove Actinobacteria in Maowei Sea by Combination of Multiple Discovery Strategies

Antibiotics ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 236 ◽  
Author(s):  
Qin-Pei Lu ◽  
Jing-Jing Ye ◽  
Yong-Mei Huang ◽  
Di Liu ◽  
Li-Fang Liu ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Fluorescent Protein ◽  
Early Stage ◽  
Antibacterial Activities ◽  
Antagonistic Activity ◽  
Culture Broth ◽  
Diffusion Method ◽  
Reporter System ◽  
Mangrove Soil ◽  
New Antibiotics

Rediscovery of known antibiotics from actinobacteria, especially Streptomyces, has become a bottleneck issue. Nowadays, more specific identification and dereplication could be acquired by a combination of modern analytic techniques with various databases. In this study, 261 actinobacterial strains were isolated from 8 mangrove soil samples by culture-dependent method. A total of 83 strains were selected to evaluate antibacterial activities and mechanisms by disc diffusion method and a unique double fluorescent protein reporter system (pDualrep2), respectively. Thirty-two strains exhibited antagonistic activity against at least one of the “ESKAPE” pathogens. Four Streptomyces strains (B475, B486, B353, and B98) showed strong inhibitory activity against Gram-positive bacteria and induced DNA damage SOS response. One Micromonospora strain (B704) exhibited inhibitory activity against several pathogens and induced attenuation-based translational inhibitors reporter. Seven members of quinoxaline-type antibiotics including quinomycin A, quinomycin monosulfoxide, and other five putative new analogues were found from the culture broth of strain B475 by a combination of anti-MRSA guide, HPTLC, HPLC-UV, and UPLC-UV-HRESIMS/MS analysis, Chemspider searching, and MS/MS-based molecular networking analysis. In conclusion, this study not only demonstrated that mangrove is a rich source of actinobacteria with the potentially new antibiotics but showed rapid dereplication of known antibiotics in the early stage can improve efficiency for the discovery of new antibiotics.

A CLINICAL CASE OF PRIMARY HYPERPARATHYROIDISM OF THE OSTEO-VISCERAL FORM

2020 ◽  
pp. 155-161
Author(s):  
Poselyugina O.B. ◽  
Kulish A.S. ◽  
Vasiliev D.F.
Keyword(s):  
Primary Hyperparathyroidism ◽  
Clinical Case ◽  
Early Stage ◽  
Diagnostic Errors ◽  
Epidemiological Studies ◽  
Medical Documentation ◽  
Screening Methods ◽  
Internal Organs ◽  
Blood Calcium ◽  
Slow Development

Introduction. Primary hyperparathyroidism is an endocrine disease resulting from a primary pathology of the parathyroid gland, characterized by increased secretion of parathyroid hormone and increased blood calcium levels. Among the endocrine diseases, primary hyperparathyroidism is the third most common after diabetes mellitus and thyroid disease. In Russia, according to epidemiological studies, primary hyperparathyroidism is found in 1% of the population, women suffer 2-3 times more often than men do, and the average age of diagnosis is 54-59 years. In the absence of a timely diagnosis, primary hyperparathyroidism causes systemic damage to internal organs: renal impairment, nephrolithiasis, esophageal affection, cardiovascular and nervous system involvement, and it leads to a violation of bone tissue integrity. The aim is to demonstrate a clinical case of a patient with primary hyperparathyroidism and to analyze the stages of diagnosis of the disease and treatment. Material and methods. The review of medical literature on the problem of diagnostics and treatment of primary hyperparathyroidism was performed, as well as an analysis of the patient’s medical documentation with this pathology. Results and discussion. A variant of complicated course of primary hyperparathyroidism of bone and visceral form is considered. About 15 years passed from the moment of appearance of the first symptoms of the disease to the development of complications of renal and bone system. Despite the slow development of the disease and availability of screening methods, hyperparathyroidism was detected at the stage of complications. This article provides a detailed analysis of the primary hyperparathyroidism history, as well as analyzes the possibilities of diagnosis, treatment and prevention of this pathology. The efficacy of the therapy has been assessed, and ways of correction have been outlined. The analysis of the reasons that made it difficult to diagnose this pathology at an early stage, before the development of serious complications of internal organs, has been carried out. Conclusions: It can be assumed that the presented clinical case will increase the awareness of physicians, especially therapists, about the primary manifestations of this pathology and the peculiarities of its detection and routing the patient, which will allow avoiding many diagnostic errors.

Molecular Processes Involved in Pancreatic Cancer and Therapeutics

2020 ◽  
Vol 14 ◽  
Author(s):  
Subhajit Makar ◽  
Abhrajyoti Ghosh ◽  
Divya ◽  
Shalini Shivhare ◽  
Ashok Kumar ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Molecular Mechanisms ◽  
Early Stage ◽  
Locally Advanced ◽  
Therapeutic Strategies ◽  
Screening Methods ◽  
Pancreatic Cancer Cells ◽  
Systemic Treatments ◽  
Cancer Initiation ◽  
Novel Therapeutic Strategies

: Despite advances in the development of cytotoxic and targeted therapies, pancreatic adenocarcinoma (PAC) remains a significant cause of cancer mortality worldwide. It is also difficult to detect it at an early stage due to numbers of factors. Most of the patients are present with locally advanced or metastatic disease, which precludes curative resection. In the absence of effective screening methods, considerable efforts have been made to identify better systemic treatments during the past decade. This review describes the recent advances in molecular mechanisms involved in pancreatic cancer initiation, progression, and metastasis. Additionally, the importance of deregulated cellular signalling pathways and various cellular proteins as potential targets for developing novel therapeutic strategies against incurable forms of pancreatic cancer is reported. The emphasis is on the critical functions associated with growth factors and their receptors viz. c-MET/HGF, CTHRC1, TGF-β, JAK-STAT, cyclooxygenase pathway, WNT, CCK, MAPK-RAS-RAF, PI3K-AKT, Notch, src, IGF-1R, CDK2NA and chromatin regulation for the sustained growth, survival, and metastasis of pancreatic cancer cells. It also includes various therapeutic strategies viz. immunotherapy, surgical therapy, radiation therapy and chemotherapy.

scholarly journals Natural Products from Tongan Marine Organisms

Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4534
Author(s):  
Taitusi Taufa ◽  
Ramesh Subramani ◽  
Peter Northcote ◽  
Robert Keyzers
Keyword(s):  
Natural Products ◽  
Pacific Ocean ◽  
Biological Activities ◽  
Marine Sponges ◽  
Marine Organisms ◽  
Biologically Active ◽  
Geographic Variability ◽  
South Pacific Ocean ◽  
New Novel ◽  
Rich Diversity

The islands of the South Pacific Ocean have been in the limelight for natural product biodiscovery, due to their unique and pristine tropical waters and environment. The Kingdom of Tonga is an archipelago in the central Indo-Pacific Ocean, consisting of 176 islands, 36 of which are inhabited, flourishing with a rich diversity of flora and fauna. Many unique natural products with interesting bioactivities have been reported from Indo-Pacific marine sponges and other invertebrate phyla; however, there have not been any reviews published to date specifically regarding natural products from Tongan marine organisms. This review covers both known and new/novel Marine Natural Products (MNPs) and their biological activities reported from organisms collected within Tongan territorial waters up to December 2020, and includes 109 MNPs in total, the majority from the phylum Porifera. The significant biological activity of these metabolites was dominated by cytotoxicity and, by reviewing these natural products, it is apparent that the bulk of the new and interesting biologically active compounds were from organisms collected from one particular island, emphasizing the geographic variability in the chemistry between these organisms collected at different locations.

scholarly journals Early Detection of Alzheimer’s Disease Using Polar Harmonic Transforms and Optimized Wavelet Neural Network

2021 ◽  
Vol 11 (4) ◽  
pp. 1574
Author(s):  
Shabana Urooj ◽  
Satya P. Singh ◽  
Areej Malibari ◽  
Fadwa Alrowais ◽  
Shaeen Kalathil
Keyword(s):  
Neural Network ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Detection ◽  
Differential Evolution ◽  
Early Stage ◽  
Selection Process ◽  
Parameter Tuning ◽  
Wavelet Neural Network ◽  
Tuning Parameter

Effective and accurate diagnosis of Alzheimer’s disease (AD), as well as early-stage detection, has gained more and more attention in recent years. For AD classification, we propose a new hybrid method for early detection of Alzheimer’s disease (AD) using Polar Harmonic Transforms (PHT) and Self-adaptive Differential Evolution Wavelet Neural Network (SaDE-WNN). The orthogonal moments are used for feature extraction from the grey matter tissues of structural Magnetic Resonance Imaging (MRI) data. Irrelevant features are removed by the feature selection process through evaluating the in-class and among-class variance. In recent years, WNNs have gained attention in classification tasks; however, they suffer from the problem of initial parameter tuning, parameter setting. We proposed a WNN with the self-adaptation technique for controlling the Differential Evolution (DE) parameters, i.e., the mutation scale factor (F) and the cross-over rate (CR). Experimental results on the Alzheimer’s disease Neuroimaging Initiative (ADNI) database indicate that the proposed method yields the best overall classification results between AD and mild cognitive impairment (MCI) (93.7% accuracy, 86.0% sensitivity, 98.0% specificity, and 0.97 area under the curve (AUC)), MCI and healthy control (HC) (92.9% accuracy, 95.2% sensitivity, 88.9% specificity, and 0.98 AUC), and AD and HC (94.4% accuracy, 88.7% sensitivity, 98.9% specificity and 0.99 AUC).

Efficient Synthesis of Novel N-[4-Methyl-3-(4-(5-phenyl-1,3,4-oxadiazol-2-yl)phenyl)thiazol-2(3H)-ylidene]benzamide Hybrid Ring System as Potential Antibacterial Agents

2021 ◽  
Vol 17 ◽  
Author(s):  
Hummera Rafique ◽  
Aamer Saeed ◽  
Muhammad Naseem ◽  
Tauqeer Riaz ◽  
Fouzia Perveen ◽  
...  
Keyword(s):  
Bacterial Resistance ◽  
Antioxidant Activities ◽  
Antibacterial Properties ◽  
Antibacterial Activities ◽  
Structural Features ◽  
Ring System ◽  
Biologically Active ◽  
Thiazole Ring ◽  
Spectroscopic Techniques ◽  
Hybrid Ring

Background: Heterocyclic compounds display versatile biological applications, so the aim of this paper was to prepare biologically important heterocycles with enhanced bacterial resistance and to evaluate for their various structural features that are responsible for their biological properties. Objective: The objective was to synthesize bacterial resistance compounds with enhanced antibacterial properties. Method: Ester moiety containing thiazole ring was converted into its hydrazide derivatives. These heterocyclic derivatives were cyclized into another ring oxadiazole; hence a hybrid ring system of two biologically active rings was prepared. Result: All the synthesized compounds were characterized by spectroscopic techniques and were screened for their antibacterial potential; they possess significant antibacterial activities. Conclusion: New hybrid heterocyclic ring systems were synthesized by cyclization of hydrazide derivatives by adopting two step strategy in good yields. All the synthesized compounds were evaluated for their antioxidant activities; they showed moderate to significant activities. QSAR and Molecular docking studies were performed to determine the mode of interaction. Experimental and computational data is in accordance with the determined antibacterial activities.

scholarly journals Isolation and antimicrobial effects of endophytic fungi from Edgeworthia chrysantha

2015 ◽  
Vol 10 (3) ◽  
pp. 529 ◽  
Author(s):  
Huawei Zhang ◽  
Chuanfeng Ruan ◽  
Xuelian Bai
Keyword(s):  
Ethyl Acetate ◽  
Endophytic Fungi ◽  
Fermentation Broth ◽  
Fungal Endophytes ◽  
Antimicrobial Effect ◽  
Antibacterial Activities ◽  
Antimicrobial Activities ◽  
Human Pathogens ◽  
Antimicrobial Effects ◽  
Staphyloccocus Aureus

<p>Ten fungal strains isolated from <em>Edgeworthia chrysantha</em>, one of traditional medicinal plants in China, were evaluated their antimicrobial activities against three human pathogens, <em>Escherichia coli, Staphyloccocus aureus and Candida albicans</em>, and two phytopathogens, <em>Rhizoctonia cerealis</em> and <em>Colletotrichum gloeosporioides</em>. The results indicated that most ethyl acetate extracts of fermentation broth of these fungal endophytes had stronger antimicrobial activities than their fermentation broth. Among these endophytic strains, both fermentation broth and the ethyl acetate extract of strain D showed the strongest inhibitory effects on all pathogens. Strains 5-19 and BZ also exhibited potent antibacterial activities. However, other strains had weak or no antimicrobial effect. This was the first report on the isolation and antimicrobial effects of endophytic fungi from <em>E. chrysantha</em>.   </p><p> </p>

scholarly journals Involvement of a Nonstructural Protein in Poliovirus Capsid Assembly

2018 ◽  
Vol 93 (5) ◽  
Author(s):  
Oluwapelumi O. Adeyemi ◽  
Lee Sherry ◽  
Joseph C. Ward ◽  
Danielle M. Pierce ◽  
Morgan R. Herod ◽  
...  
Keyword(s):  
Early Stage ◽  
Selection Process ◽  
Nonstructural Protein ◽  
Infectious Clone ◽  
Regulatory Protein ◽  
Lethal Mutation ◽  
Site Directed Mutagenesis ◽  
Coding Region ◽  
Virion Assembly ◽  
Vp1 Protein

ABSTRACTVirus capsid proteins must perform a number of roles. These include self-assembly and maintaining stability under challenging environmental conditions, while retaining the conformational flexibility necessary to uncoat and deliver the viral genome into a host cell. Fulfilling these roles could place conflicting constraints on the innate abilities encoded within the protein sequences. In a previous study, we identified a number of mutations within the capsid-coding sequence of poliovirus (PV) that were established in the population during selection for greater thermostability by sequential treatment at progressively higher temperatures. Two mutations in the VP1 protein acquired at an early stage were maintained throughout this selection procedure. One of these mutations prevented virion assembly when introduced into a wild-type (wt) infectious clone. Here we show, by sequencing beyond the capsid-coding region of the heat-selected virions, that two mutations had arisen within the coding region of the 2A protease. Both mutations were maintained throughout the selection process. Introduction of these mutations into a wt infectious clone by site-directed mutagenesis considerably reduced replication. However, they permitted a low level of assembly of infectious virions containing the otherwise lethal mutation in VP1. The 2Apromutations were further shown to slow the kinetics of viral polyprotein processing, and we suggest that this delay improves the correct folding of the mutant capsid precursor protein to permit virion assembly.IMPORTANCERNA viruses, including poliovirus, evolve rapidly due to the error-prone nature of the polymerase enzymes involved in genome replication. Fixation of advantageous mutations may require the acquisition of complementary mutations which can act in concert to achieve a favorable phenotype. This study highlights a compensatory role of a nonstructural regulatory protein, 2Apro, for an otherwise lethal mutation of the structural VP1 protein to facilitate increased thermal resistance. Studying how viruses respond to selection pressures is important for understanding mechanisms which underpin emergence of resistance and could be applied to the future development of antiviral agents and vaccines.

scholarly journals Pharmacological studies of Mangifera indica leaf extract

2021 ◽  
Vol 7 (3) ◽  
pp. 073-079
Author(s):  
Agrawal RC
Keyword(s):  
Hydroxyl Radical ◽  
Radical Scavenging Activity ◽  
Mangifera Indica ◽  
Radical Scavenging ◽  
Antibacterial Activities ◽  
Positive Control ◽  
Screening Methods ◽  
Phytochemical Screening ◽  
Test Organisms ◽  
Almost All

The present study was undertaken to explore the phytochemical screening, anti-bacterial and anti-oxidant activities of the hydro-methanolic leaves extract of Mangifera indica using standard screening methods such as disc diffusion and DPPH methods. In phytochemical screening, Mangifera indicaextract showed presence of secondary metabolites such as carbohydrate, phenols, tanins and proteins whereas Saponins were absent. It also showed antibacterial activities against almost all the test organisms. The extracts possessed potent hydroxyl radical scavenging activity against the positive control standard Ascorbic acid. Results denote the presence of hydroxyl radical scavenging principles in the extracts.

Sign in / Sign up

Export Citation Format

Share Document