Pulmonary tuberculosis is a highly prevalent respiratory disease that affects approximately a quarter of the world's population. The drug treatment protocol for tuberculosis is complex because the ...Mycobacterium tuberculosis (M. tuberculosis) invades macrophages and begins to infect. Thus treatment usually includes combination therapy with several drugs such as rifampicin, pyrazinamide, isoniazid, and ethambutol over a long dosing period. Therefore, drug-delivery technologies have been developed to improve patient compliance with medication, reduce adverse effects, and increase effectiveness of the treatment. In the present review, we have discussed recent inhalable nanopharmaceutical systems for the treatment of pulmonary tuberculosis and investigated their design and effectiveness. We examined the underlying processes and characteristics of spray-drying technology and studied the formulation of a dry carrier using spray-drying method. Moreover, we reviewed various research articles on pulmonary delivery of nanoparticles using these carriers, and studied their alveolar macrophage targeting ability and therapeutic effects. Further, we appraised the effectiveness of nanoparticle inhalation therapy for the treatment of pulmonary tuberculosis and its potential as a treatment strategy for lung diseases.
Biomineralization, the process by which minerals are deposited by organisms, has attracted considerable attention because this mechanism has shown great potential to inspire bottom-up material ...syntheses. To understand the mechanism for morphological regulation that occurs during biomineralization, many regulatory proteins have been isolated from various biominerals. However, the molecular mechanisms that regulate the morphology of biominerals remain unclear because there is a lack of in vivo evidence. Magnetotactic bacteria synthesize intracellular magnetosomes that comprise membrane-enveloped single crystalline magnetite (Fe3O4). These nano-sized magnetite crystals (<100 nm) are bacterial species dependent in shape and size. Mms6 is a protein that is tightly associated with magnetite crystals. Based on in vitro experiments, this protein was first implicated in morphological regulation during nano-sized magnetite biomineralization. In this study, we analyzed the mms6 gene deletion mutant (Δmms6) of Magnetospirillum magneticum (M. magneticum) AMB-1. Surprisingly, the Δmms6 strain was found to synthesize the smaller magnetite crystals with uncommon crystal faces, while the wild-type and complementation strains synthesized highly ordered cubo-octahedral crystals. Furthermore, deletion of mms6 gene led to drastic changes in the profiles of the proteins tightly bound to magnetite crystals. It was found that Mms6 plays a role in the in vivo regulation of the crystal structure to impart the cubo-octahedral morphology to the crystals during biomineralization in magnetotactic bacteria. Magnetotactic bacteria synthesize magnetite crystals under ambient conditions via a highly controlled morphological regulation system that uses biological molecules.
Cancer-derived circulating exosomes or nanoscale extracellular vesicles are emerging biomarkers for disease detection and treatment because of their cell-specific constituents and unique ...intercellular pathways. For efficient exosome isolation from bio-fluids, the design of high-affinity nanointerfaces is of great importance in the development of miniaturized systems for the collection of exosomes. Herein, we report peptide-functionalized nanowires as a biorecognition interface for the capture and release of cancer-derived exosomes within a microfluidic channel. Based on the amino-acid sequence of EWI-2 protein, a partial peptide that bound to the CD9 exosome marker and thus targeted cancer exosomes was screened. Linkage of the exosome-targeting peptide with a ZnO-binding sequence allowed one-step and reagent-free peptide modification of the ZnO nanowire array. As a result of peptide functionalization, the exosome-capturing ability of ZnO nanowires was significantly improved. Furthermore, the captured exosomes could be subsequently released from the nanowires under a neutral salt condition for downstream applications. This engineered surface that enhances the nanowires' efficiency in selective and controllable collection of cancer-derived exosomes provides an alternative foundation for developing microfluidic platforms for exosome-based diagnostics and therapeutics.
Membrane curvature-sensing (MCS) proteins recognize and regulate the morphologies of biological membranes. As these proteins lack characteristic sequence motifs in their primary structure, they are ...not instantly recognizable by genomic databases. Overcoming this technological challenge toward the agile identification of new proteins can promote the elucidation of membrane morphological regulation. Here, for the selective identification of MCS proteins, comparative proteomic analysis was performed using different sizes of the spherical supported lipid bilayer (SSLB), which consists of spherical SiO2 particles covered with a lipid bilayer. Because of the presence of SiO2 core, the curvature of the surrounding membrane is well-controlled and stable even on a micron scale. To prove this concept, known membrane curvature-sensing protein domains, Bin/Amphiphysin/Rvs (BAR) and Epsin N-terminal homology (ENTH), were evaluated by performing a binding assay using SSLBs, and the preferential binding to the highly curved membrane was confirmed. Peripheral membrane proteins obtained from normal human dermal fibroblast (NHDF) and human breast cancer (MDA-MB-231) cells were used in shotgun proteomic analysis, and 786 and 949 proteins were identified from SSLBs as lipid membrane binders, respectively. Statistical quantitative analyses of proteins detected from each SSLB with a different size revealed 118 candidate proteins, including 23 proteins unique to MDA-MB-231 cells, as membrane curvature sensors, including some previously reported curvature sensors. Functional clustering analysis based on the KEGG orthology database revealed that the protein-binding property to specific high or low membrane curvature correlated with their functions. Further investigation of candidate proteins will lead to the identification of new MCS proteins as well as cancer biomarkers.
For the past 200 years, lactate has been regarded as a metabolic waste end product that causes fatigue during exercise. However, lactate production is closely correlated with energy metabolism. The ...lactate dehydrogenase-catalyzed reaction uses protons to produce lactate, which delays ongoing metabolic acidosis. Of note, lactate production differs depending on exercise intensity and is not limited to muscles. Importantly, controlling physiological effect of lactate may be a solution to alleviating some chronic diseases. Released through exercise, lactate is an important biomarker for fat oxidation in skeletal muscles. During recovery after sustained strenuous exercise, most of the lactate accumulated during exercise is removed by direct oxidation. However, as the muscle respiration rate decreases, lactate becomes a desirable substrate for hepatic glucose synthesis. Furthermore, improvement in brain function by lactate, particularly, through the expression of vascular endothelial growth factor and brain-derived neurotrophic factor, is being increasingly studied. In addition, it is possible to improve stress-related symptoms, such as depression, by regulating the function of hippocampal mitochondria, and with an increasingly aging society, lactate is being investigated as a preventive agent for brain diseases such as Alzheimer's disease. Therefore, the perception that lactate is equivalent to fatigue should no longer exist. This review focuses on the new perception of lactate and how lactate acts extensively in the skeletal muscles, heart, brain, kidney, and liver. Additionally, lactate is now used to confirm exercise performance and should be further studied to assess its impact on exercise training.
Oleaginous photosynthetic organisms such as microalgae are promising sources for biofuel production through the generation of carbon-neutral sustainable energy. However, the metabolic mechanisms ...driving high-rate lipid production in these oleaginous organisms remain unclear, thus impeding efforts to improve productivity through genetic modifications. We analyzed the genome and transcriptome of the oleaginous diatom Fistulifera solaris JPCC DA0580. Next-generation sequencing technology provided evidence of an allodiploid genome structure, suggesting unorthodox molecular evolutionary and genetic regulatory systems for reinforcing metabolic efficiencies. Although major metabolic pathways were shared with nonoleaginous diatoms, transcriptome analysis revealed unique expression patterns, such as concomitant upregulation of fatty acid/triacylglycerol biosynthesis and fatty acid degradation (β-oxidation) in concert with ATP production. This peculiar pattern of gene expression may account for the simultaneous growth and oil accumulation phenotype and may inspire novel biofuel production technology based on this oleaginous microalga.
Dipeptidyl peptidase IV (DPP-IV) has become an important target in the prevention and treatment of diabetes. Although many DPP-IV inhibitory peptides have been identified by a general approach ...involving the repeated fractionation of food protein hydrolysates, the obtained results have been dependent on the content of each peptide and fractionation conditions. In the present study, a peptide array that provides comprehensive assays of peptide sequences was used to identify novel DPP-IV inhibitory peptides derived from bovine milk proteins; these peptides were then compared with those identified using the general approach. While the general approach identified only known peptides that were abundant in the hydrolysate, the peptide array-based approach identified 10 novel DPP-IV inhibitory peptides, all of which had proline at the second residue from the N-terminus. The proper or combined use of these two approaches, which have different advantages, will enable the efficient development of novel bioactive foods and drugs.
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•Peptide array can be used to screen DPP-IV inhibitory peptides from food proteins.•Ten novel DPP-IV inhibitory peptides were identified.•All the novel peptides contained a proline at the second residue from the N-terminus.
A CD9-binding peptide (RSHRLRLH), screened from EWI-2, was characterized, and its effect on cellular migration and invasion was evaluated. As CD9 protein is overexpressed in cancer cells and plays an ...important role in cellular migration, the CD9-binding peptide preferentially inhibited the migration of cancer cells. Unlike conventional antiproliferative drugs, this CD9-binding peptide is promising as a novel precision antimigratory agent for cancer therapeutics.
A CD9-binding peptide (RSHRLRLH), screened from EWI-2, was characterized, and its inhibition effect on cancer-cell migration and invasion was demonstrated.
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Diseases caused by antibiotic-resistant bacteria are challenging to treat, and biofilms, which are polymeric conglomerations of bacterial extracellular polysaccharides, proteins, ...lipids, and DNA, form rigid barriers that prevent external antibacterial reagents from penetrating. In synergy, antibiotic-resistant bacteria and biofilms are highly resistant to chemicals and antibiotics. To eliminate bacterial biofilms, we prepared silver nanoparticles on graphene oxide (GO) nanosheets to synergistically increase the efficacy of bacterial killing and biofilm removal with the minimum amount of toxicity to mammalian cells. Silver nanoparticles prepared on GO nanosheets were characterized by X-ray diffraction, transmission electron microscopy, and inductively coupled plasma-mass spectrometry. Antibacterial activity was evaluated by colony counting assay and minimum inhibitory concentrations against common bacteria. Finally, the antibiofilm properties of nanocomposites were tested in a microfluidic channel with biofilms formed along channel walls. This study shows the potential of silver nanoparticles on GO nanosheets to inhibit the proliferation of infectious bacteria and the formation of biofilms.
Hydroxyapatite is mineralized along the long axis of collagen fiber during osteogenesis. Mimicking such biomineralization has great potential to control inorganic structures and is fast becoming an ...important next-generation inorganic synthesis method. Inorganic matter synthesized by biomineralization can have beautiful and functional structures that cannot be created artificially. In this study, we applied biomineralization to the synthesis of the only photocatalyst in practical use today, titanium dioxide (TiO2). The photocatalytic activity of TiO2 mainly relates to three properties: morphology, crystal phase, and light-use efficiency. To optimize TiO2 morphology, we used a simple sequential peptide as an organic template. TiO2 mineralized by a β-sheet peptide nanofiber template forms fiber-like shapes that are not observed for mineralization by peptides in the shape of random coils. To optimize TiO2 crystal phase, we mineralized TiO2 with the template at 400 °C to transform it into the rutile phase and at 700 °C to transform it into a mixed phase of anatase and rutile. To optimize light-use efficiency, we introduced nitrogen atoms of the peptide into the TiO2 structure as doped elemental material during sintering. Thus, this biomineralization method enables control of inorganic morphology, crystal phase, and light-use efficiency in a single process.
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