Phase I/II trials of human bone marrow-derived clonal mesenchymal stem cells for treatment of adults with moderate-to-severe atopic dermatitis.

BACKGROUND: Mesenchymal stem cells (MSCs) play important roles in therapeutic applications by regulating immune responses. OBJECTIVE: To investigate the safety and efficacy of allogenic human bone marrow-derived clonal MSCs (hcMSCs) in subjects with moderate to severe atopic dermatitis (AD). METHODS: The study included a phase I open-label trial followed by a phase II randomized, double-blind, placebo-controlled trial that involved 72 subjects with moderate to severe AD. RESULTS: In phase I, intravenous (IV) administration of hcMSCs at two doses (1×106 and 5×105 cells/kg) was safe and well-tolerated in 20 subjects. Since there was no difference between the two dosage groups (P=0.9), it was decided to administer low-dose hcMSCs only for phase II. In phase II, subjects receiving three weekly IV infusions of hcMSCs at 5x105 cells/kg showed a higher proportion of an eczema area and severity index (EASI)-50 response at week 12 compared to the placebo group (P=0.038). The differences between groups in the dermatology life quality index and pruritus numerical-rating scale scores were not statistically significant. Most adverse events were mild or moderate and resolved by the end of the study period. CONCLUSIONS: Our findings demonstrate that hcMSCs treatment resulted in a significantly higher rate of achieving EASI-50 at 12 weeks compared to the control group in subjects with moderate to severe AD. The safety profile of hcMSCs treatment was acceptable. Further larger-scale studies are necessary to confirm these preliminary findings.

The crosstalk between PTEN-induced kinase 1-mediated mitophagy and the inflammasome in the pathogenesis of alopecia areata.

Alopecia areata (AA) is a T-cell-mediated autoimmune disease that causes chronic, relapsing hair loss; however, its precise pathogenesis remains to be elucidated. Recent studies have provided compelling evidence of crosstalk between inflammasomes and mitophagy-a process that contributes to the removal of damaged mitochondria. Our previous studies showed that the NLR family pyrin domain containing 3 (NLRP3) inflammasome is important for eliciting and progressing inflammation in AA. In this study, we detected mitochondrial DNA damage in AA-affected scalp tissues and IFNγ and poly(I:C) treated outer root sheath (ORS) cells. In addition, IFNγ and poly(I:C) treatment increased mitochondrial reactive oxygen species (ROS) levels in ORS cells. Moreover, we showed that mitophagy induction alleviates IFNγ and poly(I:C)-induced NLRP3 inflammasome activation in ORS cells. Lastly, PTEN-induced kinase 1 (PINK1) knockdown increased NLRP3 inflammasome activation, indicating that PINK1-mediated mitophagy plays a critical role in NLRP3 inflammasome activation in ORS cells. This study supports previous studies showing that oxidative stress disrupts immune privilege status and promotes autoimmunity in AA. The results emphasize the significance of crosstalk between mitophagy and inflammasomes in the pathogenesis of AA. Finally, mitophagy factors regulating mitochondrial dysfunction and inhibiting inflammasome activation could be novel therapeutic targets for AA.

Knowledge and the behavioral patterns of photoprotection among Koreans with skin disease.

BACKGROUND: Photoprotection is crucial in preventing the development and progression of various skin diseases. However, patients with skin disease have limited awareness of photoprotection. We evaluated the knowledge and behavioral patterns of photoprotection among Koreans with skin diseases. METHODS: A cross-sectional study was conducted in 11 general hospitals across South Korea. The study population consisted of patients aged 19 years or older who visited dermatologic clinics for their skin diseases. A self-administered questionnaire was used to collect patient demographics, knowledge of photoprotection, and photoprotective habits. RESULTS: In this study, 1173 patients with skin cancer, hyperpigmentary disorders, hypopigmentary disorders, or other skin diseases participated. Females scored significantly higher in knowledge of photoprotection compared to males (mean score 8.4 vs. 7.8; p < .001), and younger patients (<50 years) scored higher than older patients (mean score 8.7 vs. 7.5; p < .001). Males also reported longer sun exposure times and lower usage of photoprotective measures (both p < .001). Patients with skin cancer had the lowest mean knowledge score (7.1 ± 2.6) and were less likely to use photoprotective measures compared to other groups (p < .001). In contrast, patients with hyperpigmentation actively avoided sun exposure compared with other groups (p < 0.001). CONCLUSIONS: Knowledge of photoprotection among Korean patients with skin diseases varied depending on the gender, age, and type of skin disease. Their photoprotective behaviors were inadequate, especially among males and those with skin cancer. These findings emphasize the importance of educating and tailoring photoprotection strategies for patients with skin diseases.

Efficacy and Safety of Topical Corticosteroid Treatment under Occlusion for Severe Alopecia Areata in Children. A single-center retrospective analysis.

BACKGROUND: Alopecia areata (AA) has a poor clinical course in children. There are no reliable therapeutic options for children with severe AA, including alopecia totalis (AT) and alopecia universalis (AU). AIM: We evaluated the efficacy and adverse effects of a potent topical corticosteroid (TCS) under occlusion in pediatric patients with severe AA. METHODS: We reviewed records of 23 patients under the age of 10 years with AT or AU treated with a potent TCS (0.05% clobetasol propionate or 0.3% diflucortolone valerate) for 8 hours under occlusion with a plastic film. We used the Severity of Alopecia Tool (SALT) to measure clinical improvement. The primary endpoint was a Severity of Alopecia Tool (SALT) score of 20 or less at six months. We analyzed the change in cortisol levels to identify the long-term safety of TCS therapy on the hypothalamus-pituitary-adrenal axis. RESULTS: Nineteen patients reached SALT 20 or less at the 6-month treatment. Six patients relapsed over the 6-month follow-up period. Four patients were suspected of adrenal insufficiency. However, the cortisol level of the patients recovered to normal at least 1-month after lowering TCS potency or changing to non-steroidal treatments. LIMITATIONS: Retrospective design and small sample size. CONCLUSION: This study shows that a potent TCS occlusion may be a safe treatment option in pediatric patients with severe AA. Further long-term studies are required to evaluate the safety and recurrence of TCS occlusion therapy for pediatric AA.

Customized Reconstruction of Lower Eyelid Defects.

BACKGROUND: A lower eyelid defect is a loss of skin, muscle, and underlying structures that can occur due to trauma, malignant or benign tumors, burns, or other causes. The conventional surgical treatment of lower lid defects has several limitations, including visible scarring, narrowing of the eye, and ectropion. Here, we combined the use of a customized mid-face lift with a free mucochondral graft to overcome the disadvantages of existing methods. METHODS: Forty patients underwent reconstructive surgery using a customized mid-face lift with or without a free mucochondral graft for a lower lid defect between April 2013 and October 2020. Patients were discharged shortly after surgery and were expected to visit the outpatient clinic periodically for 12 months. RESULTS: The causes of lower eyelid defects were malignancy, trauma, foreign body granuloma, and other causes. Four patients reported complications, including 2 cases of chemosis, 1 case of a hematoma, and 1 case of corneal abrasion, who reportedly performed well after 2 weeks of conservative therapy. No patient required revision during the average follow-up period. CONCLUSIONS: Customized reconstruction demonstrated a better aesthetic reconstruction of the lower eyelid. This method represents a good option for reconstructing lower lid defects.

Effects of Midcheek Lift According to Dissection Plane and Range: An Anatomical Study.

BACKGROUND: Midcheek lift has been performed for cosmetic or reconstructive surgery of the lower eyelid. For midcheek lift through the subciliary incision, preperiosteal and subperiosteal dissections are the most often implemented, with good clinical outcomes. However, a comparative assessment of the effects of these 2 methods had not been conducted. OBJECTIVES: In this study we compared the effects of midcheek lift according to preperiosteal or subperiosteal plane and range of midfacial dissection. METHODS: Forty hemifaces of 20 fresh cadavers were dissected. One side of the hemiface underwent preperiosteal dissection, and the other side underwent subperiosteal dissection. After dissections of 5, 10, 15, 20, and 30 mm and all of the midcheek area from the inferior orbital rim, the length of the elevated lid-cheek junction was measured by placing upward traction on the lateral portion of the lower lid. RESULTS: In both methods, the length of the midcheek lift increased as the dissection progressed, and the length of the lift on the lateral side was greater than that on the medial side. The length of the pulled skin in the preperiosteal group was the greatest in most cases. However, in the full dissection cases, the midcheek lift length was not statistically different between the 2 surgical methods, especially on the lateral side. CONCLUSIONS: Flap elevation in lower blepharoplasty surgery can be predicted based on the surgical method and dissection range. Implementing a surgical plan that takes this into account can enhance both reconstruction and aesthetic surgery outcomes in the midcheek area.

Learning curve comparable study of microscopic and endoscopic type 1 tympanoplasty.

OBJECTIVES: The comparative efficacy of microscopic tympanoplasty (MT) and endoscopic tympanoplasty (ET) has been widely studied to some extent through meta-analyses. However, most studies on learning curve comparisons between the two surgeries were performed by experienced ET surgeons. We compared the surgical outcomes of MT and ET and evaluated the difference of learning curve between ET and MT performed by a single unskilled, in both MT and ET, surgeon. DESIGN: A total of 91 patients underwent ET and MT at a tertiary hospital. We reviewed the patients' medical records and analyzed all findings, including otoscopic pictures, pure tone audiometry (PTA) before and after surgery, and operation records. All operations were performed by a single otologist who had an experience of a year of otology fellowship at a tertiary university hospital. We compared the demographic and clinical characteristics, including age, sex, admission duration, and audiological outcomes before and after surgery. We also assessed the difference in the decrease in operation time. RESULTS: Among 91 patients, 44 were in the ET group and 47 were in the MT group. The mean age was 51.15 years, and 37 (40.7%) were men. Eighty-two (90.1%) patients were administered local anesthesia. Graft failure was observed in 19 (20.9%) patients, and the mean postoperative follow-up duration was 66.42 days. There were no statistically significant differences in age, sex, affected side, graft failure rate, and operation time between the ET and MT groups. There was a significant improvement in air conduction hearing and air-bone gap after surgery in both groups. Bone conduction hearing did not change before and after the surgery in either group. However, the improvement in air condition and reduction in the air-bone gap did not differ between the two groups. Multivariate linear regression analysis showed that there were no significant variables that affected operation time among age, sex, operation method (ET or MT), anesthesia, graft material, and technique. The spline regression analysis showed the decrease in operative time in ET was significantly faster than MT in the period from 8th to 19th cases. CONCLUSIONS: The surgical outcomes of ET are comparable to those of MT in terms of operation time, graft uptake, and postoperative hearing results, even in surgeons who are not experienced with both MT and ET. The operation time of ET was longer than that of MT in the early phase, and the decrease in the operating time was significantly faster in ET than in MT. Both MT and ET reached a plateau in the operation time, and this plateau appeared to be similar in both surgeries.

Epidemiology of idiopathic sudden sensorineural hearing loss in the era of big data.

OBJECTIVES: Idiopathic sudden sensorineural hearing loss (ISSNHL) is a medical emergency, and delayed treatment can have permanent sequelae. However, the etiology of ISSNHL is diverse and unclear; thus, it is idiopathic. To develop an insight into this condition, patients with ISSNHL must be clearly identified. We propose an operational definition for the unambiguous identification of ISSNHL patients. Patients are identified through suggested definitions, and prevalence and general information are investigated. METHODS: A retrospective study of patients with ISSNHL was performed using the Health Insurance and Review Assessment-National Patient Sample from 2009 to 2016. To present a new operational definition, a systematic review was conducted for studies on ISSNHL from January 2007 to June 2021. After constructing several operant definitions using the conditions that can specify patients with ISSNHL in big data, we compared each definition to propose an operational definition. RESULTS: The important conditions required to classify patients with ISSNHL using big data were the International Classification of Diseases (ICD)-10 code, number of pure tone audiometry (PTA) tests, and whether steroids were prescribed. Among them, those who had undergone PTA tests more than twice could be clearly identified as patients with ISSNHL. CONCLUSION: As the use of big data becomes smoother, research using national medical data is being conducted; however, the results of the studies may vary depending on how a patient with ISSNHL is classified. Clear identification of patients with ISSNHL will be beneficial for better management of this condition.

Primary cutaneous malignant melanoma with rhabdomyosarcomatous differentiation originating from a melanocytic nevus in a patient with myelodysplastic syndrome.

Malignant melanoma (MM) may rarely exhibit divergent differentiation, in which melanocytic markers may be lost, leading to difficulty in diagnosis. A 64-year-old man recently diagnosed with myelodysplastic syndrome complained of development of a nodule in a melanocytic nevus on his scalp. On histopathologic examination, junctional nevus nests and diffuse cellular infiltrations with a sheet-like growth pattern of pleomorphic epithelioid cells were observed in the upper dermis. Junctional nevus cells were S-100 positive, and pleomorphic epithelioid cells extending from the junctional nests were weakly positive for S-100. Large polygonal cells with eccentric nuclei and intracytoplasmic hyaline inclusions were observed in the mid to deep dermis. These rhabdomyoblast-like polygonal cells diffusely expressed desmin and were focally positive for MyoD1. Some clusters of polygonal cells in the deep dermis expressed SOX10. Collectively, these clinical and histopathologic features suggested MM with rhabdomyosarcomatous differentiation. Desmin- and skeletal-muscle-specific markers should be applied to melanocytic tumors with atypical epithelioid cells resembling rhabdomyoblasts, especially if these cells are negative for melanocytic markers.

Crucial Music Components Needed for Speech Perception Enhancement of Pediatric Cochlear Implant Users: A Systematic Review and Meta-Analysis.

BACKGROUND: Although many clinicians have attempted music training for the hearing-impaired children, no specific effects have yet been reported for individual music components. This paper seeks to discover specific music components that help in improving speech perception of children with cochlear implants (CI) and to identify the effective training periods and methods needed for each component. METHOD: While assessing 5 electronic databases, that is, ScienceDirect, Scopus, PubMed, CINAHL, and Web of Science, 1,638 articles were found initially. After the screening and eligibility assessment stage based on the Participants, Intervention, Comparisons, Outcome, and Study Design (PICOS) inclusion criteria, 18 of 1,449 articles were chosen. RESULTS: A total of 18 studies and 14 studies (209 participants) were analyzed using a systematic review and meta-analysis, respectively. No publication bias was detected based on an Egger's regression result even though the funnel plot was asymmetrical. The results of the meta-analysis revealed that the largest improvement was seen for rhythm perception, followed by the perception of pitch and harmony and smallest for timbre perception after the music training. The duration of training affected the rhythm, pitch, and harmony perception but not the timbre. Interestingly, musical activities, such as singing, produced the biggest effect size, implying that children with CI obtained the greatest benefits of music training by singing, followed by playing an instrument and achieved the smallest effect by only listening to musical stimuli. Significant improvement in pitch perception helped with the enhancement of prosody perception. CONCLUSION: Music training can improve the music perception of children with CI and enhance their speech prosody. Long training duration was shown to provide the largest training effect of the children's perception improvement. The children with CI learned rhythm and pitch better than they did with harmony and timbre. These results support the finding of past studies that with music training, both rhythm and pitch perception can be improved, and it also helps in the development of prosody perception.

Alteration of payload in extracellular vesicles by crosstalk with mesenchymal stem cells from different origin.

BACKGROUND: The application of extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) requires customized materials to target disease or cell damage. We hypothesized that EVs exert different inflammatory effects on one recipient cell, although stem cells of different origins in humans have similar payloads. RESULTS: Here, the payload of EVs released by crosstalk between MSCs and human middle ear epithelial cells (HMEECs) extracted from adipose tissue, bone marrow and tonsils significantly increased the level of anti-inflammatory factors. EVs derived from the co-culture medium decreased TNF-α, COX-2, IL-1ß, and IL-6 levels to approximately zero within 3 h in HMEECs. Expression of miR-638 and amyloid-ß A4 precursor protein-binding family A member 2 was analyzed using microarrays and gene ontology analysis, respectively. CONCLUSIONS: In conclusion, stem cells of different origins have different payloads through crosstalk with recipient-specific cells. Inducing specific factors in EVs by co-culture with MSCs could be valuable in regenerative medicine.

Protective effect of MSC-derived exosomes against cisplatin-induced apoptosis via heat shock protein 70 in auditory explant model.

Therapeutics based on stem cell technology, including stem cell-derived exosomes, have emerged in recent years for the treatment of what were otherwise considered incurable diseases. In this study, we evaluated the efficacy of human MSC-derived exosomes for protection against cisplatin induced ototoxic hearing loss. Incubation of cochlear explants with MSC-derived exosomes prior to addition of cisplatin induced a reduction in cisplatin-induced drug toxicity in auditory hair cells but not when the exosomes were introduced simultaneously with or after cisplatin. The delivery of MSC-derived exosomes to cochlear explants was confirmed by the increasing protein levels of the exosome markers CD63 and HSP70 to reduce apoptosis. These results were consistent with those from a model in which MSC-derived exosomes protect auditory hair cells from cisplatin-induced drug toxicity in an ex vivo cochlear explant model and support future studies into the therapeutic benefits of stem cell-derived exosomes in clinical applications.

Non-invasive postoperative monitoring of pedicled rat skin flap using laser speckle contrast imaging.

PURPOSE: This study used non-invasive laser speckle contrast imaging (LSCI) modality to evaluate the blood flow changes in murine flap model and to investigate the clinical feasibility of the LSCI for postoperative monitoring. METHODS: Ten of 6-8 weeks old Spraque-Dawley rats with superficial inferior epigastric vessel based pedicled skin flaps were used in this experiment. The color changes of skin flap were evaluated by naked eyes and the LSCI modality 6, 24, and 48 h after surgery. RESULTS: In vessel ligated region of skin flap, skin color began to change to a bluish color immediately postoperatively. At 24 h postoperatively, skin necrosis was detectable with the naked eye and total necrosis occurred at 48 h postoperatively. Changes in laser speckle signal were consistent with changes observed with the naked eye, and blood flow index also presented significant differences between the ligated and non-ligated region. CONCLUSION: These correlated laser speckle signal patterns suggest that non-invasive monitoring of perfusion by LSCI is a useful technology that may be used to identify the ischemic skin flap.

Improvement of stem cell-derived exosome release efficiency by surface-modified nanoparticles.

BACKGROUND: Mesenchymal stem cells (MSCs) are pluripotent stromal cells that release extracellular vesicles (EVs). EVs contain various growth factors and antioxidants that can positively affect the surrounding cells. Nanoscale MSC-derived EVs, such as exosomes, have been developed as bio-stable nano-type materials. However, some issues, such as low yield and difficulty in quantification, limit their use. We hypothesized that enhancing exosome production using nanoparticles would stimulate the release of intracellular molecules. RESULTS: The aim of this study was to elucidate the molecular mechanisms of exosome generation by comparing the internalization of surface-modified, positively charged nanoparticles and exosome generation from MSCs. We determined that Rab7, a late endosome and auto-phagosome marker, was increased upon exosome expression and was associated with autophagosome formation. CONCLUSIONS: It was concluded that the nanoparticles we developed were transported to the lysosome by clathrin-mediated endocytosis. additionally, entered nanoparticles stimulated that autophagy related factors to release exosome from the MSC. MSC-derived exosomes using nanoparticles may increase exosome yield and enable the discovery of nanoparticle-induced genetic factors.

Induced Short-Term Hearing Loss due to Stimulation of Age-Related Factors by Intermittent Hypoxia, High-Fat Diet, and Galactose Injection.

Age-related hearing loss (ARHL) is the most common sensory disorder among the elderly, associated with aging and auditory hair cell death due to oxidative-stress-induced mitochondrial dysfunction. Although transgenic mice and long-term aging induction cultures have been used to study ARHL, there are currently no ARHL animal models that can be stimulated by intermittent environmental changes. In this study, an ARHL animal model was established by inducing continuous oxidative stress to promote short-term aging of cells, determined on the basis of expression of hearing-loss-induced phenotypes and aging-related factors. The incidence of hearing loss was significantly higher in dual- and triple-exposure conditions than in intermittent hypoxic conditions, high-fat diet (HFD), or d-galactose injection alone. Continuous oxidative stress and HFD accelerated cellular aging. An increase in Ucp2, usually expressed during mitochondrial dysfunction, was observed. Expression of Cdh23, Slc26a4, Kcnq4, Myo7a, and Myo6, which are ARHL-related factors, were modified by oxidative stress in the cells of the hearing organ. We found that intermittent hypoxia, HFD, and galactose injection accelerated cellular aging in the short term. Thus, we anticipate that the development of this hearing loss animal model, which reflects the effects of intermittent environmental changes, will benefit future research on ARHL.

KLF4 suppresses the tumor activity of cutaneous squamous cell carcinoma (SCC) cells via the regulation of SMAD signaling and SOX2 expression.

Kruppel-like factor 4 (KLF4) is a zinc-finger transcription factor that plays a role in terminal differentiation of epidermal keratinocytes. There are conflicting reports regarding the role of KLF4 in tumor development, with both the tumor suppressive and/or oncogenic properties depending on different conditions and cell types. In this study, we investigated the functional importance of KLF4 in cutaneous squamous cell carcinoma (SCC). Immunohistochemistry showed that KLF4 expression was relatively low in SCC lesion compared to normal epidermis. To examine the effects of KFL4, we transduced SCC lines (SCC12 and SCC13 cells) with the KLF4-expressing recombinant adenovirus. Overexpression of KLF4 significantly decreased cell proliferation and colony forming activity. In addition, overexpression of KLF4 markedly reduced invasive potential, along with the downregulation of epithelial-mesenchymal transition (EMT)-related molecules. In a mechanistic study, KLF4 inhibited SOX2, of which expression is critical for tumor initiation and growth of SCC. Further investigations indicated that SOX2 expression is induced by TGF-ß/SMAD signaling, and that overexpression of KLF4 inhibited SMAD signaling via upregulation of SMAD7, an important inhibitory SMAD molecule. Based on these data, KLF4 plays a tumor suppressive role in cutaneous SCC cells.

Chondritis of the ear after docetaxel-carboplatin chemotherapy.

Docetaxel, derived from the yew tree, belongs to the taxane family of medications. It works by disrupting the normal function of microtubules, thereby stopping cell division. Docetaxel is used in the treatment of ovarian, breast, esophageal, gastric, prostate, lung, and head and neck cancers. Common side effects include hair loss, low blood cell counts, peripheral neuropathy, vomiting, and muscle pain. Auricular chondritis with ear deformity has not been reported previously as a side effect of docetaxel. In this paper, we present the case of a 64-year-old male patient with chondritis accompanied by ear deformity that developed due to docetaxel-carboplatin chemotherapy for non-small cell lung cancer.

Evaluation of wireless Bluetooth devices to improve recognition of speech and sentences when using a mobile phone in bone conduction device recipients.

OBJECTIVE: To evaluate the effect of a wireless Bluetooth device (WBD) in word and sentence recognition in patients with bone conduction devices (BCDs) while using mobile phones. METHODS: We performed a prospective study evaluating speech and sentence recognition in both quiet and noised conditions. A total of nine patients, audiologically eligible for BCDs, were included. Based on their hearing impairment type and severity, subjects were divided into "BCD only" and "BCD with HA" groups. The speech and sentence recognition scores of each condition were compared by nonparametric methods. RESULTS: Both the "BCD only" and "BCD with HA" groups had higher scores in the quiet condition than in the noised condition in word and sentence recognition tests, irrespective of whether the WBD was used. The benefit from using a WBD was greater in the noised condition. There were significant differences in the word recognition test results before and after using the WBD in the "BCD only" group, and in both the word and sentence recognition tests results before and after using the WBD bimodally in the noised condition in the "BCD with HA" group. CONCLUSION: WBDs improve word and sentence recognition in adult BCD bone recipients when they use mobile phones. WBD use provides additional benefits in "BCD with HA" patients in a bimodal situation.

Circulating Serum miRNA-205 as a Diagnostic Biomarker for Ototoxicity in Mice Treated with Aminoglycoside Antibiotics.

BACKGROUND: To confirm levels and detection timing of circulating microRNAs (miRNAs) in the serum of a mouse model for diagnosis of ototoxicity, circulating miR-205 in the serum was evaluated to reflect damages in the cochlear microstructure and compared to a kidney injury model. METHOD: A microarray for miRNAs in the serum was performed to assess the ototoxic effects of kanamycin-furosemide. Changes in the levels for the selected miRNAs (miR-205, miR-183, and miR-103) were compared in the serum and microstructures of the cochlea (stria vascularis, organ of Corti, and modiolus) between the ototoxicity and normal mouse groups. An acute kidney injury (AKI) mouse model was used to assess changes in miR-205 levels in the kidney by ototoxic drugs. RESULTS: In the mouse model for ototoxicity, the serum levels of circulating miR-205 peaked on day 3 and were sustained from days 7⁻14. Furthermore, miR-205 expression was highly expressed in the organ of Corti at day 5, continued to be expressed in the modiolus at high levels until day 14, and was finally also in the stria vascularis. The serum miR-205 in the AKI mice did not change significantly compared to the normal group. Conclusions Circulating miR-205 from the cochlea, after ototoxic damage, migrates through the blood vessels to organs, which is then finally found in blood. In conditions of hearing impairment with ototoxic medications, detection of circulating miR-205 in the blood can be used to determine the extent of hearing loss. In the future, inner ear damage can be identified by simply performing a blood test before the hearing impairment due to ototoxic drugs.

Enhanced Homing Technique of Mesenchymal Stem Cells Using Iron Oxide Nanoparticles by Magnetic Attraction in Olfactory-Injured Mouse Models.

Intranasal delivery of mesenchymal stem cells (MSCs) to the olfactory bulb is a promising approach for treating olfactory injury. Additionally, using the homing phenomenon of MSCs may be clinically applicable for developing therapeutic cell carriers. Herein, using superparamagnetic iron oxide nanoparticles (SPIONs) and a permanent magnet, we demonstrated an enhanced homing effect in an olfactory model. Superparamagnetic iron oxide nanoparticles with rhodamine B (IRBs) had a diameter of 5.22 ± 0.9 nm and ζ-potential of +15.2 ± 0.3 mV. IRB concentration of 15 µg/mL was injected with SPIONs into MSCs, as cell viability significantly decreased when 20 μg/mL was used (p ≤ 0.005) compared to in controls. The cells exhibited magnetic attraction in vitro. SPIONs also stimulated CXCR4 (C-X-C chemokine receptor type 4) expression and CXCR4-SDF-1 (Stromal cell-derived factor 1) signaling in MSCs. After injecting magnetized MSCs, these cells were detected in the damaged olfactory bulb one week after injury on one side, and there was a significant increase compared to when non-magnetized MSCs were injected. Our results suggest that SPIONs-labeled MSCs migrated to injured olfactory tissue through guidance with a permanent magnet, resulting in better homing effects of MSCs in vivo, and that iron oxide nanoparticles can be used for internalization, various biological applications, and regenerative studies.