Chemico-biological interactions
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Chem. Biol. Interact. · Sep 2019
ReviewInteractions between microbiome and lungs: Paving new paths for microbiome based bio-engineered drug delivery systems in chronic respiratory diseases.
The human body is a home to thousands of microbiotas. It is defined as a community of symbiotic, commensal and pathogenic microorganisms that have existed in all exposed sites of the body, which have co-evolved with diet, lifestyle, genetic factors and immune factors. Human microbiotas have been studied for years on their effects with relation to health and diseases. ⋯ The traditional belief of sterile lungs was challenged by the emergence of culture-independent molecular techniques and the recently introduced invasive broncho-alveolar lavage (BAL) sampling method. The constitution of a lung microbiome mainly depends on three main ecological factors, which include; firstly, the immigration of microbes into airways, secondly, the removal of microbes from airways and lastly, the regional growth conditions. In healthy conditions, the microbial communities that co-exist in our lungs can build significant pulmonary immunity and could act as a barrier against diseases, whereas, in an adverse way, microbiomes may interact with other pathogenic bacteriomes and viromes, acting as a cofactor in inflammation and host immune responses, which may lead to the progression of a disease. Thus, the use of microbiota as a target, and as a drug delivery system in the possible modification of a disease state, has started to gain massive attention in recent years. Microbiota, owing to its unique characteristics, could serve as a potential drug delivery system, that could be bioengineered to suit the interest. The engineered microbiome-derived therapeutics can be delivered through BC, bacteriophage, bacteria-derived lipid vesicles and microbe-derived extracellular vesicles. This review highlights the relationships between microbiota and different types of respiratory diseases, the importance of microbiota towards human health and diseases, including the role of novel microbiome drug delivery systems in targeting various respiratory diseases.
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Chem. Biol. Interact. · Aug 2019
Polymyxin B and polymyxin E induce anaphylactoid response through mediation of Mas-related G protein-coupled receptor X2.
Polymyxin B (PMB) and polymyxin E (PME) are cyclic, peptide antibiotics which derived from various species of Paenibacillus (Bacillus) polymyxa. They are decapeptide antibiotics with an antimicrobial spectrum that includes Gram-negative bacteria, and reused as therapeutic agents due to the emergence of multidrug-resistant (MDR) Gram-positive bacteria. PMB or PME-induced anaphylactoid reactions in the clinic have been documented. ⋯ In vivo, MRGPRB2 knockout mice exhibited lower pseudo-allergic reactions than wild type mice. Activation of MrgprB2 also triggers increased capillary permeability and paw swelling. Our results elucidated the role of MRGPRX2 in PMB and PME-induced anaphylactoid response and suggested that MRGPRX2 as a potential therapeutic target to control the anaphylactoid reactions which triggered by PMB or PME.
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Chem. Biol. Interact. · May 2019
CRMP2-derived peptide ST2-104 (R9-CBD3) protects SH-SY5Y neuroblastoma cells against Aβ25-35-induced neurotoxicity by inhibiting the pCRMP2/NMDAR2B signaling pathway.
Collapsin response mediator protein 2 (CRMP2),by regulating voltage-gated calcium channel activity, is a crucial regulator of neuronal excitability. Hyperphosphorylation of CRMP2 has been reported in brains of Alzheimer's disease (AD) patients and other neurodegenerative diseases. CRMP2 acting on N-methyl-d-aspartate receptors (NMDARs) may contribute to AD pathology. ⋯ The results show that ST2-104 significantly enhanced cell viability, inhibited cell apoptosis, decreased LDH release, suppressed the expression of the pCRMP2 protein, disrupted pCRMP2/NMDAR2B interaction, inhibited Aβ25-35-induced NMDAR currents, and decreased intracellular Ca2+ levels. The effects of ST2-104 was abolished by overexpression of CRMP2 and intensified by knockdown of CRMP2 in SH-SY5Y cells. Taken together, our results support ST2-104 as a possible biologic therapeutic in the face of Aβ25-35-induced injury via the inhibition of the pCRMP2/NMDAR2B signaling pathway.
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Chem. Biol. Interact. · Mar 2019
ReviewThe linear No-Threshold (LNT) dose response model: A comprehensive assessment of its historical and scientific foundations.
The linear no-threshold (LNT) single-hit (SH) dose response model for cancer risk assessment is comprehensively assessed with respect to its historical foundations. This paper also examines how mistakes, ideological biases, and scientific misconduct by key scientists affected the acceptance, validity, and applications of the LNT model for cancer risk assessment. In addition, the analysis demonstrates that the LNT single-hit model was inappropriately adopted for governmental risk assessment, regulatory policy, practices, and for risk communication.
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Chem. Biol. Interact. · Dec 2018
Oridonin prevents epithelial-mesenchymal transition and TGF-β1-induced epithelial-mesenchymal transition by inhibiting TGF-β1/Smad2/3 in osteosarcoma.
Osteosarcoma is the most common primary bone tumor with highly invasive characteristic and low long-term survival. Recently, epithelial-mesenchymal transition (EMT) is reported as a key event in cancer invasion and metastasis. Oridonin, a bioactive diterpenoid, has been proved to possess anti-cancer effects. ⋯ Oridonin increased the protein expression of E-cadherin and reduced N-cadherin and Vimentin. Oridonin inhibited the protein expression of Snail and Slug as well as Smad 2/3 activation. In conclusion, our study demonstrated that oridonin inhibited EMT and TGF-β1-induced EMT by inhibiting TGF-β1/Smad2/3 signaling pathway in osteosarcoma.