• BMB Reports
• /
• v.55 no.7
• /
• pp.354-359
• /
• 2022

MitoNEET, a mitochondrial outer membrane protein containing the Asn-Glu-Glu-Thr (NEET) sequence, controls the formation of intermitochondrial junctions and confers autophagy resistance. Moreover, mitoNEET as a mitochondrial substrate undergoes ubiquitination by activated Parkin during the initiation of mitophagy. Therefore, mitoNEET is linked to the regulation of autophagy and mitophagy. Mitophagy is the selective removal of the damaged or unnecessary mitochondria, which is crucial to sustaining mitochondrial quality control. In numerous human diseases, the accumulation of damaged mitochondria by impaired mitophagy has been observed. However, the therapeutic strategy targeting of mitoNEET as a mitophagy-enhancing mediator requires further research. Herein, we confirmed that mitophagy is indeed activated by mitoNEET inhibition. CCCP (carbonyl cyanide m-chlorophenyl hydrazone), which leads to mitochondrial depolarization, induces mitochondrial dysfunction and superoxide production. This, in turn, contributes to the induction of mitophagy; mitoNEET protein levels were initially increased before an increase in LC3-II protein following CCCP treatment. Pharmacological inhibition of mitoNEET using mitoNEET Ligand-1 (NL-1) promoted accumulation of Pink1 and Parkin, which are mitophagy-associated proteins, and activation of mitochondria-lysosome crosstalk, in comparison to CCCP alone. Inhibition of mitoNEET using NL-1, or mitoNEET shRNA transfected into RAW264.7 cells, abrogated CCCP-induced ROS and mitochondrial cell death; additionally, it activated the expression of PGC-1α and SOD2, regulators of oxidative metabolism. In particular, the increase in PGC-1α, which is a major regulator of mitochondrial biogenesis, promotes mitochondrial quality control. These results indicated that mitoNEET is a potential therapeutic target in numerous human diseases to enhance mitophagy and protect cells by maintaining a network of healthy mitochondria.

• Journal of Microbiology and Biotechnology
• /
• v.31 no.3
• /
• pp.398-407
• /
• 2021

Using salt-tolerant bacteria to protect plants from salt stress is a promising microbiological treatment strategy for saline-alkali soil improvement. Here, we conducted research on the growth-promoting effect of Brevibacterium frigoritolerans on wheat under salt stress, which has rarely been addressed before. The synergistic effect of B. frigoritolerans combined with representative salt-tolerant bacteria Bacillus velezensis and Bacillus thuringiensis to promote the development of wheat under salt stress was also further studied. Our approach involved two steps: investigation of the plant growth-promoting traits of each strain at six salt stress levels (0, 2, 4, 6, 8, and 10%); examination of the effects of the strains (single or in combination) inoculated on wheat in different salt stress conditions (0, 50, 100, 200, 300, and 400 mM). The experiment of plant growth-promoting traits indicated that among three strains, B. frigoritolerans had the most potential for promoting wheat parameters. In single-strain inoculation, B. frigoritolerans showed the best performance of plant growth promotion. Moreover, a pot experiment proved that the plant growth-promoting potential of co-inoculation with three strains on wheat is better than single-strain inoculation under salt stress condition. Up to now, this is the first report suggesting that B. frigoritolerans has the potential to promote wheat growth under salt stress, especially combined with B. velezensis and B. thuringiensis.

• BMB Reports
• /
• v.55 no.11
• /
• pp.547-552
• /
• 2022

Sorafenib, originally identified as an inhibitor of multiple oncogenic kinases, induces ferroptosis in hepatocellular carcinoma (HCC) cells. Several pathways that mitigate sorafenib-induced ferroptosis confer drug resistance; thus strategies that enhance ferroptosis increase sorafenib efficacy. Orphan nuclear receptor estrogen-related receptor γ (ERRγ) is upregulated in human HCC tissues and plays a role in cancer cell proliferation. The aim of this study was to determine whether inhibition of ERRγ with DN200434, an orally available inverse agonist, can overcome resistance to sorafenib through induction of ferroptosis. Sorafenib-resistant HCC cells were less sensitive to sorafenibinduced ferroptosis and showed significantly higher ERRγ levels than sorafenib-sensitive HCC cells. DN200434 induced lipid peroxidation and ferroptosis in sorafenib-resistant HCC cells. Mechanistically, DN200434 increased mitochondrial ROS generation by reducing glutathione/glutathione disulfide levels, which subsequently reduced mTOR activity and GPX4 levels. DN200434 induced amplification of the antitumor effects of sorafenib was confirmed in a tumor xenograft model. The present results indicate that DN200434 may be a novel therapeutic strategy to re-sensitize HCC cells to sorafenib.

• BMB Reports
• /
• v.55 no.11
• /
• pp.559-564
• /
• 2022

Diabetes mellitus is one of the most prevalent diseases in modern society. Many complicationssuch as hepatic cirrhosis, neuropathy, cardiac infarction, and so on are associated with diabetes. Although a relationship between diabetes and hair loss has been recently reported, the treatment of diabetic hair loss by Wnt/β-catenin activators has not been achieved yet. In this study, we found that the depilation-induced anagen phase was delayed in both db/db mice and high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic mice. In diabetic mice, both hair regrowth and wound-induced hair follicle neogenesis (WIHN) were reduced because of suppression of Wnt/β-catenin signaling and decreased proliferation of hair follicle cells. We identified that KY19382, a small molecule that activates Wnt/β-catenin signaling, restored the capabilities of regrowth and WIHN in diabetic mice. The Wnt/β-catenin signaling activator also increased the length of the human hair follicle which was decreased under high glucose culture conditions. Overall, the diabetic condition reduced both hair regrowth and regeneration with suppression of the Wnt/β-catenin signaling pathway. Consequently, the usage of Wnt/β-catenin signaling activators could be a potential strategy to treat diabetes-induced alopecia patients.

• Physical Therapy Korea
• /
• v.29 no.3
• /
• pp.171-179
• /
• 2022

Background: The application of Kinesio tape (KT) has become an alternative treatment for the reduction of edema owing to its distinct characteristics that mimic skin behavior. Although many studies have found that KT application has a positive effect on edema related to breast cancer and rehabilitation following mandibular third molar surgery, there is little evidence to support the use of KT for musculoskeletal injuries. Objects: The purpose of this study was to review the literature related to KT application for reducing edema caused by musculoskeletal disorders. Methods: A literature search (July 2022) was performed on PubMed for articles published between January 2012 and June 2022. The following keywords were used: "Kinesio taping," "Kinesio tape," "swelling," and "edema," with different combinations and derivations. Only articles available in English were included in this study. Results: Among 68 identified studies, seven met our search strategy and criteria and were included in the literature review. Five of these studies investigated musculoskeletal disorders of the knee joint; two of them reported that KT application had a positive effect on edema measured using perimetry following total knee replacement and anterior cruciate ligament reconstruction. However, the KT application did not improve swelling in patients with acute lateral ankle sprains. Pediatric patients with acute proximal phalangeal joint sprain experienced a more significant improvement in the reduction of swelling than the group using a splint. Conclusion: This literature review found discrepant evidence to support using KT for edema control in musculoskeletal disorders. Further research is needed to determine the effectiveness of KT for controlling edema following musculoskeletal injuries.

• Biomolecules & Therapeutics
• /
• v.31 no.3
• /
• pp.264-275
• /
• 2023

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by tremors, bradykinesia, and rigidity. PD is caused by loss of dopaminergic (DA) neurons in the midbrain substantia nigra (SN) and therefore, replenishment of DA neurons via stem cell-based therapy is a potential treatment option. Astrocytes are the most abundant non-neuronal cells in the central nervous system and are promising candidates for reprogramming into neuronal cells because they share a common origin with neurons. The ability of neural progenitor cells (NPCs) to proliferate and differentiate may overcome the limitations of the reduced viability and function of transplanted cells after cell replacement therapy. Achaete-scute complex homolog-like 1 (Ascl1) is a well-known neuronal-specific factor that induces various cell types such as human and mouse astrocytes and fibroblasts to differentiate into neurons. Nurr1 is involved in the differentiation and maintenance of DA neurons, and decreased Nurr1 expression is known to be a major risk factor for PD. Previous studies have shown that direct conversion of astrocytes into DA neurons and NPCs can be induced by overexpression of Ascl1 and Nurr1 and additional transcription factors genes such as superoxide dismutase 1 and SRY-box 2. Here, we demonstrate that astrocytes isolated from the ventral midbrain, the origin of SN DA neurons, can be effectively converted into DA neurons and NPCs with enhanced viability. In addition, when these NPCs are inducted to differentiate, they exhibit key characteristics of DA neurons. Thus, direct conversion of midbrain astrocytes is a possible cell therapy strategy to treat neurodegenerative diseases.

• Restorative Dentistry and Endodontics
• /
• v.48 no.2
• /
• pp.13.1-13.11
• /
• 2023

Objectives: Natural extracts have been investigated as a biomimetic strategy to mechanically strengthen the collagen network and control the biodegradation of extracellular matrix. This study evaluated the effect of epigallocatechin-3-gallate (EGCG) on abfraction lesions prior to the composite resin. Materials and Methods: The sample consisted of 30 patients (aged between 28 and 60 years) with abfraction lesions located in 2 homologous premolars. The teeth were randomly assigned according to dentin treatment: 0.02% EGCG solution or distilled water (control). After enamel acid etching, the solutions were applied immediately for 1 minute. The teeth were restored with Universal Adhesive (3M) and Filtek Z350 XT (3M). Analyzes were done by 2 independent examiners using modified USPHS (retention, secondary caries, marginal adaptation, and postoperative sensitivity) and photographic (color, marginal pigmentation, and anatomical form) criteria at baseline (7 days) and final (18 months). The data analysis used Friedman and Wilcoxon signed-rank tests (α = 0.05). Results: At baseline, all restorations were evaluated as alpha for all criteria. After 18 months, restorations were evaluated as alpha for secondary caries, color, and marginal pigmentation. There was significant difference between baseline and 18 months (p = 0.009) for marginal adaptation and postoperative sensitivity (p = 0.029), but no significant difference were verified between treatments (p = 0.433). The EGCG group had a restoration retention rate of 93.3%, while the control group had 96.7%. Conclusions: The application of EGCG solution on abfraction lesions did not significantly influence the survival of the restorations based on clinical and photographic criteria.

• Korean Journal of Pharmacognosy
• /
• v.53 no.1
• /
• pp.42-48
• /
• 2022

In order to maintain bone homeostasis, it is necessary to balance bone resorption and remodeling through the differentiation of osteoclasts that absorb old bone and osteoblasts that form new bone. However, bone resorption due to excessive osteoclast differentiation is a major cause of osteoporosis and controlling excessive osteoclast differentiation has been known as a treatment strategy for osteoporosis. Therefore, in this study, the effect of an ethanol extract of Sphaerotylus antarcticus Kirkpatrick, 1907 (SAE), polar-derived sponge with unknown biological activity, on the osteoclast differentiation process of RANKL-induced RAW264.7 cells and the generated ROS was evaluated. In the study results, SAE down-regulated the formation and function of RANKL-induced osteoclasts and osteoclast differentiation specific proteins, genes in a concentration-dependent manner. In addition, it was possible to confirm the result of restoring the lost antioxidant enzyme along with down-regulation of ROS generated by RANKL. Therefore, in this study, we propose the possibility of SAE as a potential regulator of osteoporosis due to excessive osteoclast differentiation and report the biological value of the diversity of marine-derived natural products by identifying the first biological activity against SAE that is not yet known.

• Biomolecules & Therapeutics
• /
• v.30 no.2
• /
• pp.184-190
• /
• 2022

Targeting the cystine/glutamate exchange transporter, system x_c^-, is a promising anticancer strategy that induces ferroptosis, which is a distinct form of cell death mediated by iron-dependent lipid peroxidation. The concentration of ⳑ-cystine in culture medium is higher than the physiological level. This study was aimed to evaluate the effects of ⳑ-cystine concentration on the efficacy of ferroptosis inducers in hepatocellular carcinoma cells. This study showed that treatment with sulfasalazine or erastin, a system x_c^- inhibitor, decreased the viability of Huh6 and Huh7 cells in a dose-dependent manner, and the degree of growth inhibition was greater in medium containing a physiological ⳑ-cystine concentration of 83 µM than in commercial medium with a concentration of 200 µM ⳑ-cystine. However, RSL3, a glutathione peroxidase 4 inhibitor, decreased cell viability to a similar extent in media containing both ⳑ-cystine concentrations. Sulfasalazine and erastin significantly increased the percentages of propidium iodide-positive cells in media with 83 µM ⳑ-cystine, but not in media with 200 µM ⳑ-cystine. Sulfasalazine- or erastin-induced accumulation of lipid peroxidation as monitored by C11-BODIPY probe was higher in media with 83 µM ⳑ-cystine than in media with 200 µM ⳑ-cystine. In contrast, the changes in the percentages of propidium iodide-positive cells and lipid peroxidation by RSL3 were similar in both media. These results showed that sulfasalazine and erastin, but not RSL3, were efficacious under conditions of physiological ⳑ-cystine concentration, suggesting that medium conditions would be crucial for the design of a bioassay for system x_c^- inhibitors.

• Journal of Korean Neurosurgical Society
• /
• v.65 no.3
• /
• pp.457-468
• /
• 2022

Objective : The clinical management paradigm of skull base chordomas is still challenging. Surgical resection plays an important role of affecting the prognosis. Endonasal endoscopic approach (EEA) has gradually become the preferred surgical approach in most cases, but traditional transcranial surgery cannot be completely replaced. This study presents a comparison of the results of the two surgical strategies and a summary of the treatment algorithms for skull base chordomas. Methods : We retrospectively analyzed the surgical outcomes and follow-up data of 48 patients with skull base chordomas diagnosed pathologically who received transnasal midline approaches (TMA) and transcranial lateral approaches (TLA) from 2010 to 2020. Results : Among the 48 patients, 36 cases were adopted TMA and 12 cases were performed with TLA. In terms of gross total resection (GTR) rate, 27.8% in TMA and 16.7% in TLA and with EEA alone it was increased to 38.9%, while 29.7% in primary surgery. In TMA, the cerebrospinal fluid (CSF) leak remains the most common complication (13 cases, 36.1%), other main complications included death, cranial nerve palsy, hypopituitarism, all the comparisons were no statistical significance. The Karnofsky Performance Scale scores in TMA were all better than those in TLA at different time, and the overall survival (OS) and recurrence free survival/progression free survival was just the reverse. Conclusion : The EEA for skull base chordomas resection has improved the GTR rate, but transcranial approach is still an alternative approach. It is necessary to select an appropriate surgical approach based on the location and the pattern of tumor growth in order to obtain the best surgical outcomes.