• Journal of Industrial and Engineering Chemistry
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• v.67
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• pp.469-477
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• 2018

We describe surgical sutures enabled with the local, sustained delivery of a TGF-${\beta}$ inhibitory drug, tranilast. To fabricate drug-delivery sutures, we separately prepared a tranilast-loaded strand using poly (lactic-co-glycolic acid), which was then physically braided with a surgical suture already in clinical use. By this method, the drug-delivery sutures maintained the mechanical strength and allowed the modulation of drug release profiles by simply altering the tranilast-loaded strand. The drug-delivery sutures herein released tranilast for up to 14 days. When applied to animal models, scarring was indeed reduced with diminished TGF-${\beta}$ expression and fibroblast numbers during the entire 21 day testing period.

• Journal of Biomedical Engineering Research
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• v.42 no.3
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• pp.116-124
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• 2021

It is important to differentiate between the target tissue (or organ) and the rest of the tissue before incision during surgery. And when it is necessary to preserve the differentiated tissues, the blood vessels connected to the tissue must be preserved together. Various non-invasive medical imaging methods have been developed for this purpose. We aimed to develop a medical imaging system that can simultaneously apply fluorescence imaging using indocyanine green (ICG) and laser speckle contrast imaging (LSCI) using laser speckle patterns. We designed to collect images directed to the two cameras on a co-axial optical path and to compensate equal optical path length for two optical designs. The light source used for fluorescence and LSCI the same 785 nm wavelength. This system outputs real-time images and is designed to intuitively distinguish target tissues or blood vessels. This system outputs LSCI images up to 37 fps through parallel processing. Fluorescence for ICG and blood flow in animal models were observed throughout the experiment.

• BMB Reports
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• v.55 no.3
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• pp.136-141
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• 2022

Inflammation is one of the body's natural responses to injury and illness as part of the healing process. However, persistent inflammation can lead to chronic inflammatory diseases and multi-organ failure. Altered mitochondrial function has been implicated in several acute and chronic inflammatory diseases by inducing an abnormal inflammatory response. Therefore, treating inflammatory diseases by recovering mitochondrial function may be a potential therapeutic approach. Recently, mitochondrial transplantation has been proven to be beneficial in hyperinflammatory animal models. However, it is unclear how mitochondrial transplantation attenuates inflammatory responses induced by external stimuli. Here, we isolated mitochondria from umbilical cord-derived mesenchymal stem cells, referred as to PN-101. We found that PN-101 could significantly reduce LPS-induced mortality in mice. In addition, in phorbol 12-myristate 13-acetate (PMA)-treated THP-1 macrophages, PN-101 attenuated LPS-induced increase production of pro-inflammatory cytokines. Furthermore, the anti-inflammatory effect of PN-101 was mediated by blockade of phosphorylation, nuclear translocation, and trans-activity of NFκB. Taken together, our results demonstrate that PN-101 has therapeutic potential to attenuate pathological inflammatory responses.

• Journal of Microbiology and Biotechnology
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• v.32 no.5
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• pp.621-629
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• 2022

Bacterial outer membrane vesicles (OMVs) typically contain multiple immunogenic molecules that include antigenic proteins, making them good candidates for vaccine development. In animal models, vaccination with OMVs has been shown to confer protective immune responses against many bacterial diseases. It is possible to genetically introduce heterologous protein antigens to the bacterial host that can then be produced and relocated to reside within the OMVs by means of the host secretion mechanisms. Accordingly, in this study we sought to develop a novel platform for recombinant OMV (rOMV) production in the widely used bacterial expression host species, Escherichia coli. Three different lipoprotein signal peptides including their Lol signals and tether sequences-from Neisseria meningitidis fHbp, Leptospira interrogans LipL32, and Campylobactor jejuni JlpA-were combined upstream to the GFPmut2 model protein, resulting in three recombinant plasmids. Pilot expression studies showed that the fusion between fHbp and GFPmut2 was the only promising construct; therefore, we used this construct for large-scale expression. After inducing recombinant protein expression, the nanovesicles were harvested from cell-free culture media by ultrafiltration and ultracentrifugation. Transmission electron microscopy demonstrated that the obtained rOMVs were closed, circular single-membrane particles, 20-200 nm in size. Western blotting confirmed the presence of GFPmut2 in the isolated vesicles. Collectively, although this is a non-optimized, proof-of-concept study, it demonstrates the feasibility of this platform in directing target proteins into the vesicles for OMV-based vaccine development.

• The Journal of Internal Korean Medicine
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• v.43 no.4
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• pp.503-513
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• 2022

Objectives: The antitussive, expectorant, and anti-inflammatory effects of Mahwangyounpae-tang (MHYPT) aqueous extracts were observed in appropriate animal models of various respiratory disorders. Methods: MHYPT aqueous extracts were orally administered once a day for 11 days at dose levels of 400, 200, and 100 mg/kg. The effect of MHYPT was determined by comparing its antitussive effect with theobromine (TB), its expectorant effect with ambroxol (AM), and its anti-inflammatory effect with dexamethasone (DEXA). Results: MHYPT aqueous extracts (400 mg/kg) showed favorable antitussive effects comparable to those of TB (50 mg/kg) in the NH₄OH-exposure coughing mouse model and expectorant effects comparable to those of AM (250 mg/kg) in the phenol red-secretion mouse model, but MHYPT (400 mg/kg) showed less anti-inflammatory activity compared to DEXA (1 mg/kg) in the xylene-induced acute inflammatory mouse ear model under the experimental conditions used. Conclusion: MHYPT aqueous extracts administered at dosage levels of 400, 200, and 100 mg/kg induced dose-dependent and favorable antitussive, expectorant, and anti-inflammatory activities that occurred by simultaneous modulation of the activity of mast cells and respiratory mucous production under the experimental conditions used in this study.

• Journal of Veterinary Science
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• v.21 no.3
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• pp.42.1-42.22
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• 2020

Regenerative medicine using stem cells from various sources are emerging treatment modality in several refractory diseases in veterinary medicine. It is well-known that stem cells can differentiate into specific cell types, self-renew, and regenerate. In addition, the unique immunomodulatory effects of stem cells have made stem cell transplantation a promising option for treating a wide range of disease and injuries. Recently, the medical demands for companion animals have been rapidly increasing, and certain disease conditions require alternative treatment options. In this review, we focused on stem cell application research in companion animals including experimental models, case reports and clinical trials in dogs and cats. The clinical studies and therapeutic protocols were categorized, evaluated and summarized according to the organ systems involved. The results indicate that evidence for the effectiveness of cell-based treatment in specific diseases or organ systems is not yet conclusive. Nonetheless, stem cell therapy may be a realistic treatment option in the near future, therefore, considerable efforts are needed to find optimized cell sources, cell numbers and delivery methods in order to standardize treatment methods and evaluation processes.

• Biomolecules & Therapeutics
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• v.30 no.5
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• pp.391-398
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• 2022

Polyploidization is a process by which cells are induced to possess more than two sets of chromosomes. Although polyploidization is not frequent in mammals, it is closely associated with development and differentiation of specific tissues and organs. The liver is one of the mammalian organs that displays ploidy dynamics in physiological homeostasis during its development. The ratio of polyploid hepatocytes increases significantly in response to hepatic injury from aging, viral infection, iron overload, surgical resection, or metabolic overload, such as that from non-alcoholic fatty liver diseases (NAFLDs). One of the unique features of NAFLD is the marked heterogeneity of hepatocyte nuclear size, which is strongly associated with an adverse liver-related outcome, such as hepatocellular carcinoma, liver transplantation, and liver-related death. Thus, hepatic polyploidization has been suggested as a potential driver in the progression of NAFLDs that are involved in the control of the multiple pathogenicity of the diseases. However, the importance of polyploidy in diverse pathophysiological contexts remains elusive. Recently, several studies reported successful improvement of symptoms of NAFLDs by reducing pathological polyploidy or by controlling cell cycle progression in animal models, suggesting that better understanding the mechanisms of pathological hepatic polyploidy may provide insights into the treatment of hepatic disorders.

• Biomolecules & Therapeutics
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• v.31 no.1
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• pp.1-15
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• 2023

Autophagy is a process of eliminating damaged or unnecessary proteins and organelles, thereby maintaining intracellular homeostasis. Deregulation of autophagy is associated with several diseases including cancer. Contradictory dual roles of autophagy have been well established in cancer. Cytoprotective mechanism of autophagy has been extensively investigated for overcoming resistance to cancer therapies including radiotherapy, targeted therapy, immunotherapy, and chemotherapy. Selective autophagy inhibitors that directly target autophagic process have been developed for cancer treatment. Efficacies of autophagy inhibitors have been tested in various pre-clinical cancer animal models. Combination therapies of autophagy inhibitors with chemotherapeutics are being evaluated in clinal trials. In this review, we will focus on genetical and pharmacological perturbations of autophagy-related proteins in different steps of autophagic process and their therapeutic benefits. We will also summarize combination therapies of autophagy inhibitors with chemotherapies and their outcomes in pre-clinical and clinical studies. Understanding of current knowledge of development, progress, and application of cytoprotective autophagy inhibitors in combination therapies will open new possibilities for overcoming drug resistance and improving clinical outcomes.

• Biomolecules & Therapeutics
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• v.31 no.2
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• pp.148-160
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• 2023

Depression is a neuropsychiatric disorder associated with persistent stress and disruption of neuronal function. Persistent stress causes neuronal atrophy, including loss of synapses and reduced size of the hippocampus and prefrontal cortex. These alterations are associated with neural dysfunction, including mood disturbances, cognitive impairment, and behavioral changes. Synaptic plasticity is the fundamental function of neural networks in response to various stimuli and acts by reorganizing neuronal structure, function, and connections from the molecular to the behavioral level. In this review, we describe the alterations in synaptic plasticity as underlying pathological mechanisms for depression in animal models and humans. We further elaborate on the significance of phytochemicals as bioactive agents that can positively modulate stress-induced, aberrant synaptic activity. Bioactive agents, including flavonoids, terpenes, saponins, and lignans, have been reported to upregulate brain-derived neurotrophic factor expression and release, suppress neuronal loss, and activate the relevant signaling pathways, including TrkB, ERK, Akt, and mTOR pathways, resulting in increased spine maturation and synaptic numbers in the neuronal cells and in the brains of stressed animals. In clinical trials, phytochemical usage is regarded as safe and well-tolerated for suppressing stress-related parameters in patients with depression. Thus, intake of phytochemicals with safe and active effects on synaptic plasticity may be a strategy for preventing neuronal damage and alleviating depression in a stressful life.