Influence of frailty status on the health-related quality of life in older patients with chronic low back pain: a retrospective observational study.

PURPOSE: Understanding the influence of frailty on health-related quality of life (HRQoL) in older individuals experiencing chronic low back pain can provide valuable insights into the impact of frailty. Therefore, the aim of our study is to assess how different frailty statuses among older outpatients with chronic low back pain affect their HRQoL. METHODS: Patients aged 60 and above with chronic low back pain were recruited from March 2022 to February 2023. Frailty was assessed via the frailty phenotype questionnaire, and HRQoL was evaluated using the EQ-5D-5L. Multiple regression models were used to explore the influence of frailty status on the EQ-5D-5L index and EQ-VAS. Logistic regression was used to determine odds ratios for the impact of frailty status on belonging to the lowest EQ-5D-5L index quartile. RESULTS: A total of 1,054 participants were classified into robust (29.8%), pre-frail (47.7%), and frail (22.5%) groups. Frailty was significantly associated with declining HRQoL. Pre-frail and frail statuses were inversely linked to the EQ-5D-5L index, with significantly higher odds of scoring in the lowest quartile compared to robust individuals. Stratification analysis identified sex as an effect modifier, emphasizing a more substantial association between frailty and the lowest EQ-5D-5L index quartile in female patients. CONCLUSIONS: A significant association exists between frailty and reduced HRQoL in patients with chronic low back pain. This association was predominant in female patients. Furthermore, considering the dynamic nature of frailty, early detection and effective interventions targeting pre-frailty are essential to delaying the transition to full frailty and improving HRQoL.

Effect of Retrograde Autologous Priming on Coagulation Assessed by Rotation Thromboelastometry in Patients Undergoing Valvular Cardiac Surgery.

OBJECTIVES: To investigate the effect of retrograde autologous priming (RAP) on coagulation function using rotation thromboelastometry (ROTEM) in patients undergoing valvular cardiac surgery. DESIGN: A prospective, randomized, patient- and outcome assessor-blinded study. SETTING: At a single-center university hospital. PARTICIPANTS: Patients aged 20 years or older undergoing valvular cardiac surgery. INTERVENTIONS: A total of 104 patients were allocated to the RAP or control group (1:1 ratio). In the RAP group, the prime was displaced into the collection bag before bypass initiation. ROTEM was performed at the induction of anesthesia, at the beginning of rewarming, and after the reversal of heparinization. Allogeneic plasma products and platelet concentrates were transfused according to ROTEM-based algorithms. MEASUREMENTS AND MAIN RESULTS: An average volume of 635 ± 114 mL was removed using RAP (from the 1,600 mL initial prime volume). The hematocrit 10 minutes after cardiopulmonary bypass (CPB) was 24.7 ± 3.5% in the control group, and 26.1 ± 4.1% in the RAP group (p = 0.330). ROTEM, including EXTEM, INTEM, and FIBTEM, showed prolonged clotting time and decreased maximal clot firmness after CPB in both groups without intergroup differences. The number of patients who received intraoperative erythrocytes (27% v 25%, control versus RAP, p = 0.823), fresh frozen plasma (14% v 8%, control versus RAP, p = 0.339), cryoprecipitate (21% v 12%, control versus RAP, p = 0.185), or platelet concentrate transfusion (19% v 12%, control versus RAP, p = 0.277) did not differ between the groups. CONCLUSIONS: Cardiopulmonary bypass induced impaired coagulation function on ROTEM. However, RAP did not improve coagulation function when compared with conventional priming in patients undergoing valvular cardiac surgery.

Identifying high-risk factors and mitigation strategies for acrylamide formation in air-fried lotus root chips: Impact of cooking parameters, including temperature, time, presoaking, and seasoning.

This study was conducted to identify high-risk factors and mitigation strategies for acrylamide formation in air-fried lotus root chips by studying the impact of various cooking parameters, including temperature, time, presoaking, and pre-seasoning treatments. The temperature and time had a surprisingly high impact on acrylamide formation. The chips prepared at high temperatures with longer cooking times contained an extremely high acrylamide content, reaching 12,786 ng/g (e.g., 170°C/19 min). A particularly concerning discovery was that the chips with extremely high acrylamide content (up to 17 times higher than the EU benchmark level for potato chips) did not appear overcooked or taste burnt. Higher cooking temperatures required shorter cooking times to properly cook lotus root chips for consumption. A high temperature with a short cooking time (170°C/13 min) greatly benefited acrylamide reduction compared to low temperature with a long cooking time (150°C/19 min). Presoaking in a 0.1% acetic acid solution and pre-seasoning with 1% salt reduced acrylamide levels by 61% and 47%, respectively. However, presoaking in water, vinegar solution, and citric acid solution did not significantly decrease the acrylamide content in the chips. Furthermore, some seasonings significantly increased acrylamide levels (up to 7.4 times higher). For the first time, these findings underscore the high risks associated with air-frying lotus root chips without considering these factors. This study also provides proper air-frying parameters and pretreatment strategies for minimizing acrylamide formation in air-fried lotus chips.

Use of Baclofen as a Treatment for Nocturnal Calf Cramps in Individuals With Lumbar Spinal Stenosis: A Prospective Randomized Study.

OBJECTIVE: This study aimed to compare the efficacy and safety of baclofen and gabapentin in reducing leg pain from nocturnal calf cramps in lumbar spinal stenosis patients. DESIGN: In a randomized clinical trial, the patients with lumbar spinal stenosis who commonly experienced nocturnal calf cramps were included. Patients were randomly assigned to either the baclofen or gabapentin group. Overall leg pain intensity, nocturnal calf cramp frequency and severity, sleep disturbances and functional disability were assessed at baseline and after 4 and 12 wks. RESULTS: Thirty-six patients completed the 3-mo study. Both gabapentin and baclofen groups showed a significant reduction in overall leg pain, calf cramp frequency and intensity, and insomnia severity index scores from baseline to the endpoint. However, there were no significant differences between the two groups in terms of symptom reduction at different time points. The baclofen group also demonstrated a significant decrease in Oswestry Disability Index scores ( P < 0.001), while the gabapentin group did not ( P = 0.344). No adverse effects were reported in either group. CONCLUSIONS: Baclofen seems to be as effective and as safe as gabapentin in treating nocturnal calf cramps in lumbar spinal stenosis patients and even shows superiority in enhancing functional outcomes.

Identification of intracellular activation mechanism of rhamnogalacturonan-I type polysaccharide purified from Panax ginseng leaves in macrophages and roles of component sugar chains on activity.

This study aimed to investigate the mechanisms underlying intracellular signaling pathways in macrophages in relation to the structural features of rhamnogalacturonan (RG) I-type polysaccharide (PGEP-I) purified from Panax ginseng leaves. For this investigation, we used several specific inhibitors and antibodies against mitogen-activated protein kinase (MAPK), nuclear factor-kappa B (NF-κB), and pattern recognition receptors (PRRs). Furthermore, we investigated the roles of component sugar chains on immunostimulating activity through a sequential enzymatic and chemical degradation steps. We found that PGEP-I effectively induced the phosphorylation of several MAPK- and NF-κB-related proteins, such as p38, cJun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK), and p65. Particularly, immunocytochemistry analysis confirmed the PGEP-I-induced translocation of p65 into the nucleus. Furthermore, the breakdown of PGEP-I side chains and main chain during sequential enzymatic and chemical degradation reduced the PGEP-I-induced macrophage cytokine secretion activity. IL-6, TNF-α, and NO secreted by macrophages are associated with several signaling pathway proteins such as ERK, JNK, and NF-κB and several PRRs such as dectin-1, CD11b, CD14, TLR2, TLR4, and SR. Thus, these findings suggest that PGEP-I exerts potent macrophage-activating effects, which can be attributed to its typical RG-I structure comprising arabinan, type II arabinogalactan, and rhamnose-galacturonic acid repeating units in the main chain.

Long-term follow-up of inpatients with traumatic fractures who received integrative Korean Medicine treatment: A retrospective analysis and questionnaire survey study.

Previous studies have reported pain reduction after Korean medicine (KM) treatment in patients with fractures. However, these studies were limited by small sample sizes and short observation periods. To address these limitations, we aimed to analyze the outcomes of patients with traumatic fractures who received integrative KM treatment and investigate their long-term progress through follow-up observations. This study was a retrospective analysis and questionnaire survey conducted at a multi-center inpatient care setting in Korea. A total of 1150 patients who had traumatic fractures and received at least 5-day inpatient care at one of 5 KM hospitals. Finally, 339 patients completed the follow-up survey. The questionnaire survey was administered 3 months post discharge. The primary outcome was the difference in numeric rating scale (NRS) scores at admission and discharge for fracture-related pain. The secondary outcomes were EuroQol 5-Dimension 5-Level (EQ-5D-5L) score, Oswestry Disability Index, Neck Disability Index, Western Ontario and McMaster Universities Arthritis Index, Shoulder Pain and Disability Index, and Patient Global Impression of Change (PGIC) score. The follow-up questionnaire survey included questions on surgery and imaging before admission and after discharge and treatment within the past 3 months. The mean NRS score at follow-up showed a significant decrease of 4.41 points compared with that at admission (P < .001). The mean EQ-5D-5L score at follow-up showed a significant increase of 0.18 points compared with that at admission (P < .05). In the follow-up survey on PGIC, 307 participants (90.56%) were "minimally improved" or better. Integrative KM treatment can help improve pain, functional impairment, and long-term quality of life in patients with traumatic fractures.

Toward economical application of carbon capture and utilization technology with near-zero carbon emission.

Carbon capture and utilization technology has been studied for its practical ability to reduce CO2 emissions and enable economical chemical production. The main challenge of this technology is that a large amount of thermal energy must be provided to supply high-purity CO2 and purify the product. Herein, we propose a new concept called reaction swing absorption, which produces synthesis gas (syngas) with net-zero CO2 emission through direct electrochemical CO2 reduction in a newly proposed amine solution, triethylamine. Experimental investigations show high CO2 absorption rates (>84%) of triethylamine from low CO2 concentrated flue gas. In addition, the CO Faradaic efficiency in a triethylamine supplied membrane electrode assembly electrolyzer is approximately 30% (@-200 mA cm-2), twice higher than those in conventional alkanolamine solvents. Based on the experimental results and rigorous process modeling, we reveal that reaction swing absorption produces high pressure syngas at a reasonable cost with negligible CO2 emissions. This system provides a fundamental solution for the CO2 crossover and low system stability of electrochemical CO2 reduction.

Adaptive Data Selection-Based Machine Learning Algorithm for Prediction of Component Obsolescence.

Product obsolescence occurs in the manufacturing industry as new products with better performance or improved cost-effectiveness are developed. A proactive strategy for predicting component obsolescence can reduce manufacturing losses and lead to customer satisfaction. In this study, we propose a machine learning algorithm for a proactive strategy based on an adaptive data selection method to forecast the obsolescence of electronic diodes. Typical machine learning algorithms construct a single model for a dataset. By contrast, the proposed algorithm first determines a mathematical cover of the dataset via unsupervised clustering and subsequently constructs multiple models, each of which is trained with the data in one cover. For each data point in the test dataset, an optimal model is selected for regression. Results of empirical experiments show that the proposed method improves the obsolescence prediction accuracy and accelerates the training procedure. A novelty of this study is that it demonstrates the effectiveness of unsupervised clustering methods for improving supervised regression algorithms.

Forecasting Obsolescence of Components by Using a Clustering-Based Hybrid Machine-Learning Algorithm.

Product obsolescence occurs in every production line in the industry as better-performance or cost-effective products become available. A proactive strategy for obsolescence allows firms to prepare for such events and reduces the manufacturing loss, which eventually leads to positive customer satisfaction. We propose a machine learning-based algorithm to forecast the obsolescence date of electronic diodes, which has a limitation on the amount of data available. The proposed algorithm overcomes these limitations in two ways. First, an unsupervised clustering algorithm is applied to group the data based on their similarity and build independent machine-learning models specialized for each group. Second, a hybrid method including several reliable techniques is constructed to improve the prediction accuracy and overcome the limitation of the lack of data. It is empirically confirmed that the prediction accuracy of the obsolescence date for the electrical component data is improved through the proposed clustering-based hybrid method.

Multiplexed targeting of miRNA-210 in stem cell-derived extracellular vesicles promotes selective regeneration in ischemic hearts.

Extracellular vesicles (EVs) are cell derivatives containing diverse cellular molecules, have various physiological properties and are also present in stem cells used for regenerative therapy. We selected a "multiplexed target" that demonstrates multiple effects on various cardiovascular cells, while functioning as a cargo of EVs. We screened various microRNAs (miRs) and identified miR-210 as a candidate target for survival and angiogenic function. We confirmed the cellular and biological functions of EV-210 (EVs derived from ASCmiR-210) secreted from adipose-derived stem cells (ASCs) transfected with miR-210 (ASCmiR-210). Under hypoxic conditions, we observed that ASCmiR-210 inhibits apoptosis by modulating protein tyrosine phosphatase 1B (PTP1B) and death-associated protein kinase 1 (DAPK1). In hypoxic endothelial cells, EV-210 exerted its angiogenic capacity by inhibiting Ephrin A (EFNA3). Furthermore, EV-210 enhanced cell survival under the control of PTP1B and induced antiapoptotic effects in hypoxic H9c2 cells. In cardiac fibroblasts, the fibrotic ratio was reduced after exposure to EV-210, but EVs derived from ASCmiR-210 did not communicate with fibroblasts. Finally, we observed the functional restoration of the ischemia/reperfusion-injured heart by maintaining the intercommunication of EVs and cardiovascular cells derived from ASCmiR-210. These results suggest that the multiplexed target with ASCmiR-210 is a useful tool for cardiovascular regeneration.

COVID-19 and Adverse Pregnancy Outcome: A Systematic Review of 104 Cases.

(1) Background: Until now, several reports about pregnant women with confirmed coronavirus disease 2019 (COVID-19) have been published. However, there are no comprehensive systematic reviews collecting all case series studies on data regarding adverse pregnancy outcomes, especially association with treatment modalities. (2) Objective: We aimed to synthesize the most up-to-date and relevant available evidence on the outcomes of pregnant women with laboratory-confirmed infection with COVID-19. (3) Methods: PubMed, Scopus, MEDLINE, Google scholar, and Embase were explored for studies and papers regarding pregnant women with COVID-19, including obstetrical, perinatal, and neonatal outcomes and complications published from 1 January 2020 to 4 May 2020. Systematic review and search of the published literature was done using the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA). (4) Results: In total, 11 case series studies comprising 104 pregnant women with COVID-19 were included in our review. Fever (58.6%) and cough (30.7%) were the most common symptoms. Other symptoms included dyspnea (14.4%), chest discomfort (3.9%), sputum production (1.0%), sore throat (2.9%), and nasal obstruction (1.0%). Fifty-two patients (50.0%) eventually demonstrated abnormal chest CT, and of those with ground glass opacity (GGO), 23 (22.1%) were bilateral and 10 (9.6%) were unilateral. The most common treatment for COVID-19 was administration of antibiotics (25.9%) followed by antivirals (17.3%). Cesarean section was the mode of delivery for half of the women (50.0%), although no information was available for 28.8% of the cases. Regarding obstetrical and neonatal outcomes, fetal distress (13.5%), pre-labor rupture of membranes (9.6%), prematurity (8.7%), fetal death (4.8%), and abortion (2.9%) were reported. There are no positive results of neonatal infection by RT-PCR. (5) Conclusions: Although we have found that pregnancy with COVID-19 has significantly higher maternal mortality ratio compared to that of pregnancy without the disease, the evidence is too weak to state that COVID-19 results in poorer maternal outcome due to multiple factors. The number of COVID-19 pregnancy outcomes was not large enough to draw a conclusion and long-term outcomes are yet to be determined as the pandemic is still unfolding. Active and intensive follow-up is needed in order to provide robust data for future studies.

Antagonistic interaction between central glucagon-like Peptide-1 and oxytocin on diet-induced obesity mice.

Glucagon-like peptide-1 (GLP-1), whose agonists are widely prescribed, is a peptide proven effective in reducing obesity. Similarly, oxytocin (OXT) is a peptide known to increase satiety and help reduce body weight. In the present study, we aimed to examine the metabolic effects of co-administration of GLP-1 and OXT in diet-induced obesity (DIO) mice to elucidate their functions and interactions in the central nervous system. To this end, 40 DIO mice were subjected to stereotaxic surgery for the installation of an osmotic minipump and intracerebroventricular administration of GLP-1, OXT, or both. Initially, it was anticipated that co-administration of these anorexigenic peptides would be as effective as, if not more than, either GLP-1 or OXT alone in providing metabolic benefits to the obese mice. Interestingly, co-administration of OXT and GLP-1 offset the reductions in body weight and food intake promoted by either peptide alone. Co-administration also negated the decrease in fat and increase in lean mass produced by either peptide alone. Moreover, co-administration showed an equivalent calorimetric benefit as either peptide alone. Therefore, these results suggest antagonistic, rather than synergistic or additive, effects of centrally administered GLP-1 and OXT that attenuate the metabolic benefits of either peptide.

Regulation of alternative macrophage activation by MSCs derived hypoxic conditioned medium, via the TGF-ß1/Smad3 pathway.

Macrophages are re-educated and polarized in response to myocardial infarction (MI). The M2 anti-inflammatory phenotype is a known dominator of late stage MI. Mesenchymal stem cells (MSCs) represent a promising tool for cell therapy, particularly heart related diseases. In general, MSCs induce alteration of the macrophage subtype from M1 to M2, both in vitro and in vivo. We conjectured that hypoxic conditions can promote secretome productivity of MSCs. Hypoxia induces TGF-ß1 expression, and TGF-ß1 mediates M2 macrophage polarization for anti-inflammation and angiogenesis in infarcted areas. We hypothesized that macrophages undergo advanced M2 polarization after exposure to MSCs in hypoxia. Treatment of MSCs derived hypoxic conditioned medium (hypo-CM) promoted M2 phenotype and neovascularization through the TGF-ß1/Smad3 pathway. In addition, hypo-CM derived from MSCs improved restoration of ischemic heart, such as attenuating cell apoptosis and fibrosis, and ameliorating microvessel density. Based on our results, we propose a new therapeutic method for effective MI treatment using regulation of macrophage polarization. [BMB Reports 2020; 53(11): 600-604].

Exosomes derived from microRNA-584 transfected mesenchymal stem cells: novel alternative therapeutic vehicles for cancer therapy.

Exosomes are small membranous vesicles which contain abundant RNA molecules, and are transferred from releasing cells to uptaking cells. MicroRNA (miRNA) is one of the transferred molecules affecting the adopted cells, including glioma cells. We hypothesized that mesenchymal stem cells (MSCs) can secrete exosomes loading miRNA and have important effects on the progress of gliomas. To determine these effects by treating exosomal miRNA in culture media of miRNA mimic transfected MSCs, we assessed the in vitro cell proliferation and invasion capabilities, and the expression level of relative proteins associated with cell apoptosis, growth and migration. For animal studies, the mice injected with U87 cells were exposed to exosomes derived from miRNA-584-5p transfected MSCs, to confirm the influence of exosomal miRNA on the progress of glioma. Based on our results, we propose a new targeted cancer therapy wherein exosomes derived from miRNA transfected MSCs could be used to modulate tumor progress as the anticancer vehicles. [BMB Reports 2018; 51(8): 406-411].

Tumor Inhibitory Effect of IRCR201, a Novel Cross-Reactive c-Met Antibody Targeting the PSI Domain.

Hepatocyte growth factor receptor (HGFR, c-Met) is an essential member of the receptor tyrosine kinase (RTK) family that is often dysregulated during tumor progression, driving a malignant phenotypic state and modulating important cellular functions including tumor growth, invasion, metastasis, and angiogenesis, providing a strong rationale for targeting HGF/c-Met signaling axis in cancer therapy. Based on its protumorigenic potentials, we developed IRCR201, a potent antagonistic antibody targeting the plexin-semaphorin-integrin (PSI) domain of c-Met, using synthetic human antibody phage libraries. We characterized and evaluated the biochemical properties and tumor inhibitory effect of IRCR201 in vitro and in vivo. IRCR201 is a novel fully-human bivalent therapeutic antibody that exhibits cross-reactivity against both human and mouse c-Met proteins with high affinity and specificity. IRCR201 displayed low agonist activity and rapidly depleted total c-Met protein via the lysosomal degradation pathway, inhibiting c-Met-dependent downstream activation and attenuating cellular proliferation in various c-Met-expressing cancer cells. In vivo tumor xenograft models also demonstrated the superior tumor inhibitory responsiveness of IRCR201. Taken together, IRCR201 provides a promising therapeutic agent for c-Met-positive cancer patients through suppressing the c-Met signaling pathway and tumor growth.

The Korean Version of the Cognitive Assessment Scale for Stroke Patients (K-CASP): A Reliability and Validity Study.

OBJECTIVE: To develop the Korean version of the Cognitive Assessment Scale for Stroke Patients (K-CASP) and to evaluate the test reliability and validity of the K-CASP in stroke patients. METHODS: The original CASP was translated into Korean, back-translated into English, then reviewed and compared with the original version. Thirty-three stroke patients were assessed independently by two examiners using the K-CASP twice, with a one-day interval, for a total of four test results. To evaluate the reliability of the K-CASP, intra-class correlation coefficients were used. Pearson correlations were calculated and simple regression analyses performed with the Korean version of Mini-Mental State Examination (K-MMSE) and the aphasia quotient (AQ) to assess the validity. RESULTS: The mean score was 24.42±9.47 (total score 36) for the K-CASP and 21.50±7.01 (total score 30) for the K-MMSE. The inter-rater correlation coefficients of the K-CASP were 0.992 on the first day and 0.995 on the second day. The intra-rater correlation coefficients of the K-CASP were 0.997 for examiner 1 and 0.996 for examiner 2. In the Pearson correlation analysis, the K-CASP score significantly correlated with the K-MMSE score (r=0.825, p<0.001). The coefficients of determination (r2) of the AQ were 0.586 for the K-MMSE and 0.513 for the K-CASP in the simple regression analysis. CONCLUSION: The K-CASP is a reliable and valid instrument for cognitive dysfunction screening in post-stroke patients. It is more applicable than other cognitive assessment tools in stroke patients with aphasia.

Sonographic Findings of Polyneuropathy Associated With Cerebrotendinous Xanthomatosis: A Case Report.

Cerebrotendinous xanthomatosis is a rare autosomal recessive disease that involves multiple organs, including the peripheral nervous system. The present study is the first to report the ultrasonographic findings of peripheral nerves in a patient with cerebrotendinous xanthomatosis. The patient presented with bilateral Achilles tendon enlargement and foot hypesthesia. Sonographic examination revealed hypoechoic, swollen peripheral nerves with enlarged bilateral Achilles tendons. Since the ultrasonographic findings revealed peripheral involvement, the diagnosis of cerebrotendinous xanthomatosis was established after laboratory and genetic studies along with clinical findings.

Prescription patterns for patients with schizophrenia in Korea: a focus on antipsychotic polypharmacy.

OBJECTIVE: This study investigated the prescription patterns for Korean patients with schizophrenia with a particular focus on antipsychotic polypharmacy. All data were gathered from patients presenting at 41 tertiary university hospitals and 8 secondary hospitals. METHODS: Data from three multicenter studies conducted in Korea were retrospectively reviewed and integrated to identify patients with schizophrenia who had their antipsychotic medication switched to paliperidone extended-release between 2008 and 2009. The rates for antipsychotic polypharmacy, combined use of different antipsychotic classes with a special focus on atypical antipsychotics, and psychotropic polypharmacy using benzodiazepines, mood stabilizers, and other relevant drugs were identified. RESULTS: Of the 851 Korean patients analyzed in this study, 20.4% (n=173) had been prescribed antipsychotic polypharmacy. Of the 678 patients receiving antipsychotic monotherapy, 6.9% (n=47) were prescribed a typical antipsychotic and 93.1% (n=631) were prescribed an atypical antipsychotic. Of the 173 patients receiving a combination of antipsychotic drugs, only 6.4% (n=11) had been prescribed polypharmacy with typical antipsychotics, while 46.82% (n=81) were prescribed atypical+atypical antipsychotics or typical+atypical antipsychotics. The highest co-prescription rates for other psychotropic drugs in conjunction with antipsychotics included benzodiazepines (30.3%), anticholinergic drugs (28.8%), antidepressants (13.3%), ß-blockers (10.1%), and mood stabilizers (8.7%). CONCLUSION: The present findings demonstrate that the rate of antipsychotic polypharmacy is relatively low in Korea and that Korean clinicians prefer to prescribe atypical, rather than typical, antipsychotic drugs. This suggests that there is a distinct prescription pattern in Korea that is focused on antipsychotic polypharmacy.

MHY884, a newly synthesized tyrosinase inhibitor, suppresses UVB-induced activation of NF-κB signaling pathway through the downregulation of oxidative stress.

The skin is the primary target of prolonged and repeated ultraviolet (UVB) irradiation which induces cutaneous inflammation and pigmentation. Nuclear factor κB (NF-κB) is the major factor mediating UVB-induced inflammatory responses through the expression of various proinflammatory proteins such as inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). We have previously reported that the synthetic novel compound 4-(5-chloro-2,3-dihydrobenzo[d]thiazol-2-yl)-2,6-dimethoxyphenol (MHY884) strongly suppressed tyrosinase activity and melanin synthesis in B16F10 melanoma cells. In the present study, we investigated the effect of MHY884 on the inhibition of UVB-induced NF-κB activation and its proinflammatory downstream proteins through the suppression of oxidative stress in an in vivo model of photoaging. Generation of reactive oxygen species (ROS) and peroxynitrite was measured in vitro and in B16F10 melanoma cells to verify the scavenging activity of MHY884. MHY884 suppressed oxidative stress both in vitro and in the melanoma cells in a dose-dependent manner. Next, melanin-possessing hairless mice were pre-treated with MHY884 and then irradiated with UVB repeatedly. Topical application of MHY884 attenuated UVB-induced oxidative stress, resulting in reduced NF-κB activity. Pre-treatment with MHY884 inhibited Akt and IκB kinase α/ß signaling pathways, leading to decreased translocation and phosphorylation of p65, a subunit of NF-κB. This result correlated with the expression levels of iNOS and COX-2 in the skin of MHY884-treated mice. Thus, the novel tyrosinase inhibitor MHY884 suppressed NF-κB activation signaling pathway by scavenging UVB-induced oxidative stress. The discovery of MHY884, a novel tyrosinase inhibitor that targets NF-κB signaling, is significant, because this compound is a promising protective agent against UVB-induced skin damage.