SARS-CoV-2 infection exacerbates the cellular pathology of Parkinson's disease in human dopaminergic neurons and a mouse model.

While an association between Parkinson's disease (PD) and viral infections has been recognized, the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on PD progression remains unclear. Here, we demonstrate that SARS-CoV-2 infection heightens the risk of PD using human embryonic stem cell (hESC)-derived dopaminergic (DA) neurons and a human angiotensin-converting enzyme 2 (hACE2) transgenic (Tg) mouse model. Our findings reveal that SARS-CoV-2 infection exacerbates PD susceptibility and cellular toxicity in DA neurons pre-treated with human preformed fibrils (hPFFs). Additionally, nasally delivered SARS-CoV-2 infects DA neurons in hACE2 Tg mice, aggravating the damage initiated by hPFFs. Mice infected with SARS-CoV-2 display persisting neuroinflammation even after the virus is no longer detectable in the brain. A comprehensive analysis suggests that the inflammatory response mediated by astrocytes and microglia could contribute to increased PD susceptibility associated with SARS-CoV-2. These findings advance our understanding of the potential long-term effects of SARS-CoV-2 infection on the progression of PD.

Melatonin alleviates myocardial dysfunction through inhibition of endothelial-to-mesenchymal transition via the NF-κB pathway.

Endothelial-to-mesenchymal transition (EndMT) is a complex biological process of cellular transdifferentiation by which endothelial cells (ECs) lose their characteristics and acquire mesenchymal properties, leading to cardiovascular remodeling and complications in the adult cardiovascular diseases environment. Melatonin is involved in numerous physiological and pathological processes, including aging, and has anti-inflammatory and antioxidant activities. This molecule is an effective therapeutic candidate for preventing oxidative stress, regulating endothelial function, and maintaining the EndMT balance to provide cardiovascular protection. Although recent studies have documented improved cardiac function by melatonin, the mechanism of action of melatonin on EndMT remains unclear. The present study investigated the effects of melatonin on induced EndMT by transforming growth factor-ß2/interleukin-1ß in both in vivo and in vitro models. The results revealed that melatonin reduced the migratory ability and reactive oxygen species levels of the cells and ameliorated mitochondrial dysfunction in vitro. Our findings indicate that melatonin prevents endothelial dysfunction and inhibits EndMT by activating related pathways, including nuclear factor kappa B and Smad. We also demonstrated that this molecule plays a crucial role in restoring cardiac function by regulating the EndMT process in the ischemic myocardial condition, both in vessel organoids and myocardial infarction (MI) animal models. In conclusion, melatonin is a promising agent that attenuates EC dysfunction and ameliorates cardiac damage compromising the EndMT process after MI.

Prediction of apparent total tract digestion of crude protein in adult dogs.

To predict the apparent total tract digestibility (ATTD) of crude protein (CP) in dogs we developed an in vitro system using an in vitro digestion method and a statistical analysis. The experimental diets used chicken meat powder as the protein source, with CP levels of 20% (22.01%, analyzed CP value as dry-based), 30% (31.35%, analyzed CP value as dry-based), and 40% (41.34%, analyzed CP value as dry-based). To simulate in vivo digestive processes a static in vitro digestion was performed in two steps; stomach and small intestine. To analyze ATTD the total fecal samples were collected in eight neutered beagle dogs during the experimental period. CP digestibility was calculated by measuring CP levels in dog food, in vitro undigested fraction, and dog feces. In result, CP digestibility at both in vivo and in vitro was increased with increasing dietary CP levels. To estimate in vivo digestibility the co-relation of in vivo ATTD and in vitro digestibility was investigated statistically and a regression equation was developed to predict the CP ATTD (% = 2.5405 × in vitro CP digestibility (%) + 151.8). The regression equation was evaluated its feasibility by using a commercial diet. The predicted CP digestibility which was calculated by the regression equation showed high index of similarity (100.16%) with that of in vivo in dogs. With that, it would be a feasible non-animal method to predict in vivo CP digestibility by using in vitro digestion method and the proposed linear regression equation in adult dogs.

Perceived personal and contextual impunity: Conceptualization, antecedents, and implications for workplace misconduct.

Scholarship on impunity has centered around quantifiable prosecutions related to criminal acts that often occur outside of the workplace. We offer insights into the psychological experience of impunity by shifting the focus to organizational settings and embedding impunity within discussions of workplace misconduct. We distinguish between (a) perceived personal impunity, which reflects employees' belief that they will not face punishment for their own misconduct; and (b) perceived contextual impunity, which reflects employees' belief that their organization will not punish employees for their misconduct. We develop and validate measures for each impunity perception and establish a preliminary nomological network by investigating factors that influence each perception and their relationship with workplace misconduct. Consequently, we offer nuanced insights into how distinct impunity perceptions result in workplace misconduct relative to other established predictors. Our perceived workplace impunity measures provide a valuable tool for assessing impunity perceptions and predicting instances of misconduct. In addition, they offer practical insights into impunity's functions within organizations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Atypical Gradenigo's syndrome in a pediatric case: A critical review of neuroimaging.

Gradenigo's syndrome, a rare but serious complication of otitis media, encompasses a triad of symptoms including otalgia, facial palsy, and abducens nerve palsy, pointing to the involvement of the petrous apex. This case report presents an 11-year-old boy with an atypical manifestation of Gradenigo's syndrome, characterized by the absence of classic features such as abducens nerve palsy and purulent otorrhea. MRI findings were significant for petrous apicitis extending to Meckel's cave and the cavernous sinus, along with abscess formation and clivus osteomyelitis. The report highlights the critical role of advanced neuroimaging, particularly MRI, in the diagnosis and management of this condition. It underscores the importance of recognizing atypical presentations of Gradenigo's syndrome and the effectiveness of imaging-guided conservative treatment strategies in pediatric otological cases.

Simple modeling of familial Alzheimer's disease using human pluripotent stem cell-derived cerebral organoid technology.

BACKGROUND: Cerebral organoids (COs) are the most advanced in vitro models that resemble the human brain. The use of COs as a model for Alzheimer's disease (AD), as well as other brain diseases, has recently gained attention. This study aimed to develop a human AD CO model using normal human pluripotent stem cells (hPSCs) that recapitulates the pathological phenotypes of AD and to determine the usefulness of this model for drug screening. METHODS: We established AD hPSC lines from normal hPSCs by introducing genes that harbor familial AD mutations, and the COs were generated using these hPSC lines. The pathological features of AD, including extensive amyloid-ß (Aß) accumulation, tauopathy, and neurodegeneration, were analyzed using enzyme-linked immunosorbent assay, Amylo-Glo staining, thioflavin-S staining, immunohistochemistry, Bielschowsky's staining, and western blot analysis. RESULTS: The AD COs exhibited extensive Aß accumulation. The levels of paired helical filament tau and neurofibrillary tangle-like silver deposits were highly increased in the AD COs. The number of cells immunoreactive for cleaved caspase-3 was significantly increased in the AD COs. In addition, treatment of AD COs with BACE1 inhibitor IV, a ß-secretase inhibitor, and compound E, a γ-secretase inhibitor, significantly attenuated the AD pathological features. CONCLUSION: Our model effectively recapitulates AD pathology. Hence, it is a valuable platform for understanding the mechanisms underlying AD pathogenesis and can be used to test the efficacy of anti-AD drugs.

Factors associated with health-related quality of life on mental and oral health in patients with cancer and cancer survivors using the Korea National Health and Nutrition Examination Survey (2005-2018).

Objective: To investigate the association of mental and oral health with the health-related quality of life (HRQOL) in patients with cancer and cancer survivors. Methods: This cross-sectional study involved 1643 patients with cancer and 1628 individuals who survived cancer (aged ≥ 19 years) using data from the 2005-2018 Korean National Health and Nutrition Examination Survey. The data were analyzed using SAS survey procedures (version 9.4), t-tests, χ2 test, and multiple regression. Results: Regarding differences in mental and oral health factors by group, the results revealed significant differences between depression, suicidal ideation, subjective oral health, chewing problems, and speaking problems due to oral issues. The HRQOL of patients with cancer was lower than that of cancer survivors. The factors influencing HRQOL in both patients with cancer and cancer survivors were education status, economic activity, subjective health, suicidal ideation, and speaking problems due to oral issues. HRQOL was also associated with depression in patients with cancer. Conclusions: Patients with cancer had a lower HRQOL than cancer survivors. The two groups of patients showed significant differences in the factors associated with HRQOL. Therefore, customized health programs and policies should be developed and implemented for each group to improve their QOL.

Demographic review of aesthetic surgery for patients with facial palsy.

BACKGROUND: This study analyzed the demographic characteristics of patients with facial palsy who were treated using either dynamic or static procedures. This study aimed to compare the frequency of procedure implementation and age distribution between the two groups. METHODS: This study retrospectively analyzed the medical records of patients treated for facial palsy at a single institution from 2014 to 2022. Among cases included in our study, dynamic procedures involved cross-facial nerve graft and latissimus dorsi or gracilis muscle flap transfer. Static procedures included gold weight insertion, canthopexy, browlift, and thread lift/static slings. RESULTS: Among the 31 patients included in our study, eight (25.8%) incorporated dynamic techniques, and the average age of patients was 44.75 years (range, 24-68 years) with a male to female ratio of 1:4. The remaining 23 patients (74.2%) underwent a static procedure, of which the average age was 59.17 years (range, 23-81 years) which was statistically significantly higher than the average age of 44.75 of dynamic patients (p= 0.013). Regarding the timing of treatment after diagnosis, no patient underwent dynamic procedures more than 20 years after initial diagnosis. A greater diversity in the timing of treatment was observed in the static group. All patients who underwent dynamic procedures were treated using static procedures during the study period. CONCLUSION: Because aesthetics-based static techniques are typically quick outpatient procedures that can be performed under local anesthesia, our study shows that these are often preferred treatments for all age groups, especially for debilitated or older patients. Further research is required to investigate the long-term functional outcomes of these surgical techniques in a wider population of patients.

Surface-functionalized SERS platform for deep learning-assisted diagnosis of Alzheimer's disease.

Early diagnosis of Alzheimer's disease is crucial to stall the deterioration of brain function, but conventional diagnostic methods require complicated analytical procedures or inflict acute pain on the patient. Then, label-free Surface-enhanced Raman spectroscopy (SERS) analysis of blood-based biomarkers is a convenient alternative to rapidly obtain spectral information from biofluids. However, despite the rapid acquisition of spectral information from biofluids, it is challenging to distinguish spectral features of biomarkers due to interference from biofluidic components. Here, we introduce a deep learning-assisted, SERS-based platform for separate analysis of blood-based amyloid ß (1-42) and metabolites, enabling the diagnosis of Alzheimer's disease. SERS substrates consisting of Au nanowire arrays are fabricated and functionalized in two characteristic ways to compare the validity of different Alzheimer's disease biomarkers measured on our SERS system. The 6E10 antibody is immobilized for the capture of amyloid ß (1-42) and analysis of its oligomerization process, while various self-assembled monolayers are attached for different dipole interactions with blood-based metabolites. Ultimately, SERS spectra of blood plasma of Alzheimer's disease patients and human controls are measured on the substrates and classified via advanced deep learning techniques that automatically extract informative features to learn generalizable representations. Accuracies up to 99.5% are achieved for metabolite-based analyses, which are verified with an explainable artificial intelligence technique that identifies key spectral features used for classification and for deducing significant biomarkers.

Educational Outcomes and Perception Changes in Medical Students After Visiting a Blood Donation Center.

Educating primary care physicians about blood donation and transfusion is critical. The Division of Hematology and Oncology at Soonchunhyang University Seoul Hospital in Korea introduced an on-site educational program termed the Blood Donation Center Visiting Program in the clerkship education for final-year medical students. We evaluated the educational outcomes and changes in perception among medical students after the Blood Donation Center Visiting Program based on a survey. The program was implemented from 2021 to 2023. As part of the program, students visited a blood donation center each week, one group at a time. They gained practical knowledge about the blood donation process, and some students actively participated in blood donation. After the program, 287 students were eligible for an online survey of the program, of whom 203 participated in the survey. Among the 203 students, 126 (62.1%) donated blood during their visit to the blood donation center as part of the program, and 88.7% of the students reported an increase (from 71.4% to 90.1%) in their knowledge and willingness to donate blood. The on-site educational Blood Donation Center Visiting Program appears to have generated positive changes in perceptions among students and enhanced their knowledge about blood donation.

Evaluating total organic carbon as an indicator for organic pollutant management in the marine environment: A case study on wastewater treatment plant effluent input into the coastal ocean.

South Korea recently shifted its assessment indicator for organic matter in terrestrial environments from chemical oxygen demand (COD) to total organic carbon (TOC) due to the increase in refractory organic carbon levels. However, in the marine environment, where the inflow of refractory organic matter is also on the rise, COD is still used in some instances to assess organic pollution in contaminated areas. Our findings reveal that the main source of dissolved organic carbon (DOC) is terrestrial-derived refractory organic carbon, which enters through nearby wastewater treatment plant (WWPT) outlets. The low oxidation efficiency of COD to TOC (approximately 4 %) prevents it from being an accurate measure of terrestrial-derived refractory DOC. Contrasting results were observed when comparing the organic pollution index (OPI), which we calculated using TOC, with the currently employed water quality index (WQI) for ocean water quality evaluation, particularly in areas influenced by WWPTs. This discrepancy arises because the WQI primarily evaluates autochthonous organic carbon through chlorophyll measurements, whereas the OPI incorporates both autochthonous and allochthonous organic carbon through TOC measurements. Our findings demonstrate that TOC can effectively replace COD as an organic pollution indicator in marine environments.

Real-world outcomes of third-line immune checkpoint inhibitors versus irinotecan-based chemotherapy in patients with advanced gastric cancer: a Korean, multicenter study (KCSG ST22-06).

BACKGROUND: Immune checkpoint inhibitor (ICI) or irinotecan-based chemotherapy is frequently used after failure of second-line paclitaxel plus ramucirumab treatment for patients with locally advanced unresectable or metastatic advanced gastric cancer (AGC). This study aimed to compare the efficacy between ICI and irinotecan-based chemotherapy as third-line treatment in patients with AGC. METHODS: We retrospectively reviewed patients with AGC, whose third-line treatment started between July 2019 and June 2021 at 17 institutions in Korea. The ICI group included patients who received nivolumab or pembrolizumab, and the irinotecan-based chemotherapy group included patients who received irinotecan or FOLFIRI (5-fluorouracil, leucovorin and irinotecan). RESULTS: A total of 363 patients [n = 129 (ICI) and n = 234 (irinotecan-based chemotherapy)] were analyzed. The median progression-free survival was 2.3 and 2.9 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.802). The median overall survival (OS) was 5.5 and 6.0 months in ICI and irinotecan-based chemotherapy groups, respectively (p = 0.786). For all patients included in this study, multivariable analysis showed that weight loss, peritoneal metastasis, low serum sodium or albumin, and short duration of second-line treatment were associated with inferior OS (p < 0.05). ICI showed significantly longer OS than irinotecan-based chemotherapy in patients without peritoneal metastasis. Whereas ICI showed significantly shorter OS in patients without PD-L1 expression than irinotecan-based chemotherapy. CONCLUSIONS: No significant difference in survival outcome was observed between ICI and irinotecan-based chemotherapy as third-line treatment for AGC patients. ICI might be preferred for patients without peritoneal metastasis and irinotecan-based chemotherapy for patients with tumors without PD-L1 expression. TRIAL REGISTRATION: This study was registered in the Clinical Trial Registry of Korea ( https://cris.nih.go.kr : KCT 0007732).

RFX4 is an intrinsic factor for neuronal differentiation through induction of proneural genes POU3F2 and NEUROD1.

Proneural genes play a crucial role in neuronal differentiation. However, our understanding of the regulatory mechanisms governing proneural genes during neuronal differentiation remains limited. RFX4, identified as a candidate regulator of proneural genes, has been reported to be associated with the development of neuropsychiatric disorders. To uncover the regulatory relationship, we utilized a combination of multi-omics data, including ATAC-seq, ChIP-seq, Hi-C, and RNA-seq, to identify RFX4 as an upstream regulator of proneural genes. We further validated the role of RFX4 using an in vitro model of neuronal differentiation with RFX4 knock-in and a CRISPR-Cas9 knock-out system. As a result, we found that RFX4 directly interacts with the promoters of POU3F2 and NEUROD1. Transcriptomic analysis revealed a set of genes associated with neuronal development, which are highly implicated in the development of neuropsychiatric disorders, including schizophrenia. Notably, ectopic expression of RFX4 can drive human embryonic stem cells toward a neuronal fate. Our results strongly indicate that RFX4 serves as a direct upstream regulator of proneural genes, a role that is essential for normal neuronal development. Impairments in RFX4 function could potentially be related to the development of various neuropsychiatric disorders. However, understanding the precise mechanisms by which the RFX4 gene influences the onset of neuropsychiatric disorders requires further investigation through human genetic studies.

Ethyl acetate fraction of Osmanthus fragrans var. aurantiacus and its triterpenoids suppress proliferation and survival of colorectal cancer cells by inhibiting NF-κB and COX2.

ETHNOPHARMACOLOGICAL RELEVANCE: Colorectal cancer (CRC) remains a significant global health concern, and targeting inflammation has emerged as a promising approach for its prevention and treatment. Medicinal plants and phytochemicals have garnered attention for their potential efficacy against inflammation with minimal toxicity. Osmanthus fragrans var. aurantiacus Makino (O. fragrans) has a history of traditional use in Korea and China in treating various inflammation-related conditions, but its potential use for CRC has not been uncovered. AIM OF THE STUDY: This study aims to explore the potential anti-proliferative and pro-apoptotic properties of O. fragrans, focusing on its impact on CRC treatment. By investigating O. fragrans, we aim to uncover its anti-proliferative and apoptotic effects in human CRC cells, potentially paving the way for effective and well-tolerated therapeutic strategies for CRC patients. MATERIALS AND METHODS: Ethanol (EtOH) extracts of O. fragrans leaf and flower, along with specific fractions (n-hexane, ethyl acetate (EtOAc), n-butanol, and the aqueous residue) were evaluated for their anti-proliferative effects in human CRC cells using MTT assays, and compared to normal colon cells. Mechanistic insights and chemical profiling were obtained through flow cytometry, colorimetric assays, western blotting, and molecular docking, and high-performance liquid chromatography (HPLC) system. RESULTS: Both flower and leaf EtOH extracts of O. fragrans exhibited significant anti-proliferative effects in human CRC cells, with the leaf extract demonstrating higher potency. The EtOAc fraction from the leaf extract displayed the strongest anti-CRC cell proliferative effects while no cytotoxic effects in normal colon cells. Chemical profiling of these fractions identified triterpenoids as significant components in the EtOAc fractions. The leaf EtOAc fraction caused cell cycle arrest and apoptosis, accompanied by elevating intracellular reactive oxygen species and mitochondrial dysfunction in CRC cells. Additionally, it inhibited NF-κB and ERK1/2 signaling, leading to reduced COX2 expression. Notably, two triterpenoids isolated from the leaf EtOAc fraction, maslinic acid and corosolic acid, displayed potent anti-cancer activity in CRC cells without affecting normal colon cells. Corosolic acid exhibited a strong binding affinity to COX2 and reduced its expression, supporting its role in the anti-inflammatory and anti-cancer effects. CONCLUSIONS: Our findings suggest that O. fragrans, particularly its triterpenoid-rich EtOAc fraction, holds promise as a novel therapeutic agent for CRC prevention and therapy. These results provide valuable insights into the potential application of O. fragrans and its bioactive compounds in combating CRC.

Cancer screening through surface-enhanced Raman spectroscopy fingerprinting analysis of urinary metabolites using surface-carbonized silver nanowires on a filter membrane.

BACKGROUND: Label-free surface-enhanced Raman spectroscopy (SERS)-based metabolic profiling has great potential for early cancer diagnosis, but further advancements in analytical methods and clinical evidence studies are required for clinical applications. To improve the cancer diagnostic accuracy of label-free SERS spectral analysis of complex biological fluids, it is necessary to obtain specifically enhanced SERS signals of cancer-related metabolites present at low concentrations. RESULTS: This study presents a novel 3D SERS sensor, comprising a surface-carbonized silver nanowire (AgNW)-stacked filter membrane, alongside an optimized urine/methanol/chloroform extraction technique, which specifically changes the molecular adsorption and orientation of aromatic metabolites onto SERS substrates. By analyzing the pretreated urine samples on the surface-carbonized AgNW 3D SERS sensor, distinct and highly enhanced SERS peaks derived from semi-polar aromatic metabolites were observed for pancreatic cancer and prostate cancer samples compared with normal controls. Urine metabolite analysis using SERS fingerprinting successfully differentiated pancreatic cancer and prostate cancer groups from normal control group: normal control (n = 56), pancreatic cancer (n = 40), and prostate cancer (n = 39). SIGNIFICANCE AND NOVELTY: We confirmed the clinical feasibility of performing fingerprint analysis of urinary metabolites based on the surface-carbonized AgNW 3D SERS sensor and methanol/chloroform extraction for noninvasive cancer screening. This technology holds potential for large-scale screening owing to its high accuracy, and cost effective, simple and rapid detection method.

Increased PD-1 expression of bone marrow T-cells in acute myeloid leukaemia patients after stem cell transplantation, and its association with overall survival.

BACKGROUND: Immune checkpoints are involved in mechanisms by which tumours escape from the host immune system. Our aim was to evaluate acute myeloid leukaemia (AML) patients to determine expression levels of checkpoint molecules according to diagnosis and treatments, and to identify optimal candidates for checkpoint blockade. METHODS: Bone marrow (BM) samples were obtained from 279 AML patients at different disease status and from 23 controls. Flow cytometric analyses of PD-1 and PD-L1/PD-L2 expression were performed. RESULTS: Programmed death-1 (PD-1) expression levels on CD8+ T-cells at AML diagnosis were increased compared to controls. PD-L1 and PD-L2 expression levels on leukaemic cells at diagnosis were significantly higher in secondary AML than in de novo AML. PD-1 levels on CD8+ and CD4+ T-cells after allo-SCT were significantly higher than those at diagnosis and after CTx. PD-1 expression on CD8+ T-cells increased in the acute GVHD group than in the non-GVHD group. The overall survival of patients with high PD-1 expression on CD8+ T-cells was significantly shorter than that of patients with low PD-1 expression. CONCLUSIONS: In conclusion, patients who underwent allo-SCT exhibited high PD-1 expression, suggesting that allo-SCT increases PD-1 expression on T-cells, and the patients with high PD-1 expression on CD8+ T-cells after allo-SCT showed the poor prognosis. For these patients, PD-1 blockade could be an immunotherapeutic strategy.

A Case of Linear Hypertrophic Lichen Planus in a Pediatric Patient.

Lichen planus (LP) is a chronic inflammatory disease of the skin and mucosa. Of the various types, the hypertrophic type is characterized by thickened, purplish hyperkeratotic plaques and nodules. The course of hypertrophic LP tends to be more chronic than those of other types. A 12-year-old girl presented with a 2-year history of warty papules and plaques in a zosteriform configuration along one flank. Histopathology revealed hyperkeratosis and papillomatosis with wedge-shaped hypergranulosis. A lichenoid lymphocytic infiltrate with vacuolar change in the basal layer was evident. She was prescribed oral doxycycline, a topical corticosteroid, and tacrolimus. After 7 weeks, the skin lesions became significantly flattened and faded. LP is less common but more severe in children than in adults. The unilateral, linear hypertrophic type of LP is uncommon. Herein, we report a rare case of linear hypertrophic LP in a child.

Multi-Wavelength Photobiomodulation Ameliorates Sodium Iodate-Induced Age-Related Macular Degeneration in Rats.

Age-related macular degeneration (AMD) is a global health challenge. AMD causes visual impairment and blindness, particularly in older individuals. This multifaceted disease progresses through various stages, from asymptomatic dry to advanced wet AMD, driven by various factors including inflammation and oxidative stress. Current treatments are effective mainly for wet AMD; the therapeutic options for dry AMD are limited. Photobiomodulation (PBM) using low-energy light in the red-to-near-infrared range is a promising treatment for retinal diseases. This study investigated the effects of multi-wavelength PBM (680, 780, and 830 nm) on sodium iodate-induced oxidatively damaged retinal tissue. In an in vivo rat model of AMD induced by sodium iodate, multi-wavelength PBM effectively protected the retinal layers, reduced retinal apoptosis, and prevented rod bipolar cell depletion. Furthermore, PBM inhibited photoreceptor degeneration and reduced retinal pigment epithelium toxicity. These results suggest that multi-wavelength PBM may be a useful therapeutic strategy for AMD, mitigating oxidative stress, preserving retinal integrity, and preventing apoptosis.

Photobiomodulation Can Enhance Stem Cell Viability in Cochlea with Auditory Neuropathy but Does Not Restore Hearing.

Sensorineural hearing loss is very difficult to treat. Currently, one of the techniques used for hearing rehabilitation is a cochlear implant that can transform sound into electrical signals instead of inner ear hair cells. However, the prognosis remains very poor if sufficient auditory nerve cells are not secured. In this study, the effect of mouse embryonic stem cells (mESC) and photobiomodulation (PBM) combined treatment on auditory function and auditory nerve cells in a secondary neuropathy animal model was investigated. To confirm the engraftment of stem cells in vitro, cochlear explants were treated with kanamycin (KM) to mimic nerve damage and then cocultured with GFP-mESC. GFP-mESCs were observed to have attached and integrated into the explanted samples. An animal model for secondary neurodegeneration was achieved by KM treatment and was treated by a combination therapy of GFP-mESC and NIR-PBM at 8 weeks of KM treatment. Hearing recovery by functional testing using auditory brain stem response (ABR) and eABR was measured as well as morphological changes and epifluorescence analysis were conducted after 2 weeks of combination therapy. KM treatment elevated the hearing threshold at 70-80 dB and even after the combination treatment with GFP-mESC and PBM was applied, the auditory function was not restored. In addition, the stem cells transplanted into cochlea has exponentially increased due to PBM treatment although did not produce any malignancy. This study confirmed that the combined treatment with mESC and PBM could not improve hearing or increase the response of the auditory nerve. Nevertheless, it is noteworthy in this study that the cells are distributed in most cochlear tissues and the proliferation of stem cells was very active in animals irradiated with PBM compared to other groups wherein the stem cells had disappeared immediately after transplantation or existed for only a short period of time.

Rabbit Meat Extract Induces Browning in 3T3-L1 Adipocytes via the AMP-Activated Protein Kinase Pathway.

The browning of white adipocytes may be an innovative approach to address obesity. This study investigated the effects of rabbit meat extract on 3T3-L1 adipocytes, with a specific emphasis on inducing browning. The browning effects of rabbit meat extract were evaluated by analyzing genes specifically expressed in 3T3-L1 adipocytes using quantitative PCR and immunoblotting. Rabbit meat extract increased the expression of brown adipocyte-specific markers, UCP1 and PGC1α, and mitochondrial biogenesis factors, TFAM and NRF1, without affecting cell viability in fully differentiated 3T3-L1 adipocytes. Moreover, adipocyte differentiation and the triglyceride content were decreased; hormone-sensitive lipase activity was promoted. Rabbit meat extract activated the AMPK pathway in the differentiated 3T3-L1 cells. However, in adipocytes treated with rabbit meat extract, the expression of genes related to browning was reduced by the AMP-activated protein kinase (AMPK) inhibitor, dorsomorphin dihydrochloride. To the best of our knowledge, this is the first study to demonstrate that rabbit meat extract induces the browning of white adipocytes via the activation of the AMPK pathway, thereby demonstrating its therapeutic potential in preventing obesity.