Barcode signal amplifying strategy for sensitive and accurate protein detection on LC-MS/MS

The Analyst ◽  
2021 ◽  
Author(s):  
Chang Shu ◽  
Tengfei Li ◽  
Duo Li ◽  
Zhong-Qiu Li ◽  
Xing-Hua Xia

Protein drugs showing strong pharmaceutical activity, high specificity, low toxicity and side effects, have drawn extensive attention from the field of life science and medicine. Precise evaluation of the function...

Author(s):  
Samad Beheshtirouy ◽  
Farhad Mirzaei ◽  
Shirin Eyvazi ◽  
Vahideh Tarhriz

: Breast cancer is a heterogeneous malignancy which is the second cause of mortality among women in the world. Increasing the resistance to anti-cancer drugs in breast cancer cells persuades researchers to search the novel therapies approaches for the treatment of the malignancy. Among the novel methods, therapeutic peptides which target and disrupt tumor cells have been of great interest. Therapeutic peptides are short amino acids monomer chains with high specificity to bind and modulate a protein interaction of interest. Several advantages of peptides such as specific binding on tumor cells surface, low molecular weight and low toxicity on normal cells make the peptides as an appealing therapeutic agents against solid tumors, particularly breast cancer. Also, National Institutes of Health (NIH) describes therapeutic peptides as suitable candidate for the treatment of drug-resistant breast cancer. In this review, we attempt to review the different therapeutic peptides against breast cancer cells which can be used in treatment and diagnosis of the malignancy. Meanwhile, we presented an overview of peptide vaccines which have been developed for the treatment of breast cancer.


Pharmaceutics ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 166 ◽  
Author(s):  
Lucia Lombardi ◽  
Annarita Falanga ◽  
Valentina Del Genio ◽  
Stefania Galdiero

Peptide drugs hold great promise for the treatment of infectious diseases thanks to their novel mechanisms of action, low toxicity, high specificity, and ease of synthesis and modification. Naturally developing self-assembly in nature has inspired remarkable interest in self-assembly of peptides to functional nanomaterials. As a matter of fact, their structural, mechanical, and functional advantages, plus their high bio-compatibility and bio-degradability make them excellent candidates for facilitating biomedical applications. This review focuses on the self-assembly of peptides for the fabrication of antibacterial nanomaterials holding great interest for substituting antibiotics, with emphasis on strategies to achieve nano-architectures of self-assembly. The antibacterial activities achieved by these nanomaterials are also described.


2007 ◽  
Vol 12 (5) ◽  
pp. 311-317 ◽  
Author(s):  
Vindhya Kunduru ◽  
Shalini Prasad

We demonstrate a technique to detect protein biomarkers contained in vulnerable coronary plaque using a platform-based microelectrode array (MEA). The detection scheme is based on the property of high specificity binding between antibody and antigen similar to most immunoassay techniques. Rapid clinical diagnosis can be achieved by detecting the amount of protein in blood by analyzing the protein's electrical signature. Polystyrene beads which act as transportation agents for the immobile proteins (antigen) are electrically aligned by application of homogenous electric fields. The principle of electrophoresis is used to produce calculated electrokinetic movement among the anti-C-reactive protein (CRP), or in other words antibody funtionalized polystyrene beads. The electrophoretic movement of antibody-functionalized polystyrene beads results in the formation of “Microbridges” between the two electrodes of interest which aid in the amplification of the antigen—antibody binding event. Sensitive electrical equipment is used for capturing the amplified signal from the “Microbridge” which essentially behaves as a conducting path between the two electrodes. The technique circumvents the disadvantages of conventional protein detection methods by being rapid, noninvasive, label-free, repeatable, and inexpensive. The same principle of detection can be applied for any receptor—ligand-based system because the technique is based only on the volume of the analyte of interest. Detection of the inflammatory coronary disease biomarker CRP is achieved at concentration levels spanning over the lower microgram/milliliter to higher order nanogram/milliliter ranges.


2021 ◽  
Vol 11 (9) ◽  
pp. 1714-1721
Author(s):  
Zhijun Zhu ◽  
Da Ni ◽  
Jiping Teng ◽  
Youshuang Cheng ◽  
Bufeng Zhuang ◽  
...  

Non-small cell lung cancer (NSCLC) is still a threat to people worldwide. In the current study, we aimed to investigate the effect of folic acid (FA) and Adriamycin on NSCLC. Our work modified Adriamycin with microRNA (miR)-128-3p-loaded FA-mesoporous silica nanoparticles (MSN) (Adriamycin/miR/MSN-FA) or with Adriamycin/miR/MSN. The synthesized nanoparticles’ in vitro drug release and hydrodynamic characteristics were detected. Then Adriamycin and nanoparticles were applied to treat NSCLC cells followed by analysis of cell proliferation by MTT, cytometry and clone formation assay, apoptosis-related proteins by Western blot, and in vitro absorption by Rhodamine B staining. Animal model was set up to detect in vivo impact of nanoparticles. Adriamycin/miR/MSN-FA nanoparticles released Adriamycin in a controlled manner, inhibited colony formation and cell proliferation. Besides, nanoparticles promoted cell apoptosis and upregulated cleaved Caspase-3 and PARP. Moreover, Adriamycin/miR/MSN-FA significantly aggregated in tumor with high concentration of Adriamycin, thereby inhibiting NSCLC tumor progression with low toxicity and side effects. Adriamycin/miR/MSN-FA nanoparticles could effectively inhibit the progression of NSCLC with low toxicity and side effects.


2020 ◽  
Vol 15 (8) ◽  
pp. 1934578X2093717
Author(s):  
Chengniu Wang ◽  
Jie Hui ◽  
Xinhui Zhu ◽  
Shengyu Cui ◽  
Zhiming Cui ◽  
...  

Studies have shown that lobetyolin (LBT), a component of traditional Chinese herbal medicine, has many very good biological activities and functions. However, its side effects and toxicities have not been evaluated adequately. In this work, we investigated the effects of LBT in transgenic zebrafish. LBT treatments promoted angiogenesis and led to vascular morphological malformation in zebrafish embryos, although they were normal in appearance. Interestingly, our results indicated that LBT has a function of promoting nerve growth in the embryonic stage of zebrafish. We also treated the zebrafish with combretastatin A-4 (which resulted in neuronal apoptosis) and LBT simultaneously and found that LBT promoted nerve growth at higher concentrations. Taken together, our findings clearly display that LBT efficiently promotes angiogenesis, leading to vascular morphological malformation, has low toxicity, and notably promotes neuronal development in zebrafish.


Molecules ◽  
2019 ◽  
Vol 24 (7) ◽  
pp. 1299 ◽  
Author(s):  
Tanira Matutino Bastos ◽  
Helena Mannochio Russo ◽  
Nilmar Silvio Moretti ◽  
Sergio Schenkman ◽  
Laurence Marcourt ◽  
...  

Benznidazole and nifurtimox, the only drugs available for the treatment of Chagas disease, have limited efficacy and have been associated with severe adverse side effects. Thus, there is an urgent need to find new biotargets for the identification of novel bioactive compounds against the parasite and with low toxicity. Silent information regulator 2 (Sir2) enzymes, or sirtuins, have emerged as attractive targets for the development of novel antitrypanosomatid agents. In the present work, we evaluated the inhibitory effect of natural compounds isolated from cashew nut (Anacardium occidentale, L. Anacardiaceae) against the target enzymes TcSir2rp1 and TcSir2rp3 as well as the parasite. Two derivates of cardol (1, 2), cardanol (3, 4), and anacardic acid (5, 6) were investigated. The two anacardic acids (5, 6) inhibited both TcSir2rp1 and TcSir2rp3, while the cardol compound (2) inhibited only TcSir2rp1. The most potent sirtuin inhibitor active against the parasite was the cardol compound (2), with an EC50 value of 12.25 µM, similar to that of benznidazole. Additionally, compounds (1, 4), which were inactive against the sirtuin targets, presented anti-T. cruzi effects. In conclusion, our results showed the potential of Anacardium occidentale compounds for the development of potential sirtuin inhibitors and anti-Trypanosoma cruzi agents.


Author(s):  
Azlann Arnett ◽  
Keagan G Moo ◽  
Kaitlin J Flynn ◽  
Thomas B Sundberg ◽  
Liv Johannessen ◽  
...  

Immune health requires innate and adaptive immune cells to engage precisely balanced pro- and anti-inflammatory forces. We employ the concept of chemical immunophenotypes to classify small molecules functionally or mechanistically according to their patterns of effects on primary innate and adaptive immune cells. The high-specificity, low-toxicity cyclin dependent kinase 8 (CDK8) inhibitor DCA exerts a distinct tolerogenic profile in both innate and adaptive immune cells. DCA promotes T reg and Th2 differentiation, while inhibiting Th1 and Th17 differentiation, in both murine and human cells. This unique chemical immunophenotype led to mechanistic studies showing that DCA promotes T reg differentiation in part by regulating a previously undescribed CDK8-GATA3-FOXP3 pathway that regulates early pathways of Foxp3 expression. These results highlight previously unappreciated links between T reg and Th2 differentiation and extend our understanding of the transcription factors that regulate T reg differentiation and their temporal sequencing. These findings have significant implications for future mechanistic and translational studies of CDK8 and CDK8 inhibitors.


2020 ◽  
Author(s):  
Keying Guo ◽  
Shofarul Wustoni ◽  
Anil Koklu ◽  
Escarlet Díaz-Galicia ◽  
Maximilian Moser ◽  
...  

AbstractThe COVID-19 pandemic highlights the need for rapid protein detection and quantification at the single-molecule level in a format that is simple and robust enough for widespread point-of-care applications. We here introduce a modular nanobody-organic electrochemical transistor architecture that enables the fast and specific detection and quantification of single-molecule to nanomolar protein antigen concentrations in complex bodily fluids. The sensor combines a new solution-processable organic semiconductor material in the transistor channel with the high-density and orientation-controlled bioconjugation of nanobody fusion proteins on disposable gate electrodes. It provides results after a 10 minutes exposure to 5 µL of unprocessed samples, maintains high specificity and single-molecule sensitivity in human saliva or serum, and is rapidly reprogrammed towards any protein target for which nanobodies exist. We demonstrate the use of this highly modular platform for the detection of green fluorescent protein, SARS-CoV-1/2, and MERS-CoV spike proteins and validate the sensor for COVID-19 screening in unprocessed clinical nasopharyngeal swab and saliva samples.


2019 ◽  
Vol 27 (1) ◽  
pp. 4-16 ◽  
Author(s):  
Jaspreet Kaur Boparai ◽  
Pushpender Kumar Sharma

Antimicrobial peptides in recent years have gained increased interest among scientists, health professionals and the pharmaceutical companies owing to their therapeutic potential. These are low molecular weight proteins with broad range antimicrobial and immuno modulatory activities against infectious bacteria (Gram positive and Gram negative), viruses and fungi. Inability of micro-organisms to develop resistance against most of the antimicrobial peptide has made them as an efficient product which can greatly impact the new era of antimicrobials. In addition to this these peptides also demonstrates increased efficacy, high specificity, decreased drug interaction, low toxicity, biological diversity and direct attacking properties. Pharmaceutical industries are therefore conducting appropriate clinical trials to develop these peptides as potential therapeutic drugs. More than 60 peptide drugs have already reached the market and several hundreds of novel therapeutic peptides are in preclinical and clinical development. Rational designing can be used further to modify the chemical and physical properties of existing peptides. This mini review will discuss the sources, mechanism and recent therapeutic applications of antimicrobial peptides in treatment of infectious diseases.


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