Selective targeting of dipeptidyl-peptidase 4 (DPP-4) positive senescent chondrocyte ameliorates osteoarthritis progression.

Senescent cells increase in many tissues with age and induce age-related pathologies, including osteoarthritis (OA). Senescent chondrocytes (SnCs) are found in OA cartilage, and the clearance of those chondrocytes prevents OA progression. However, targeting SnCs is challenging due to the absence of a senescent chondrocyte-specific marker. Therefore, we used flow cytometry to screen and select senescent chondrocyte surface markers and cross-validated with published transcriptomic data. Chondrocytes expressing dipeptidyl peptidase-4 (DPP-4), the selected senescent chondrocyte-specific marker, had multiple senescence phenotypes, such as increased senescence-associated-galactosidase, p16, p21, and senescence-associated secretory phenotype expression, and showed OA chondrocyte phenotypes. To examine the effects of DPP-4 inhibition on DPP-4+ SnCs, sitagliptin, a DPP-4 inhibitor, was treated in vitro. As a result, DPP-4 inhibition selectively eliminates DPP-4+ SnCs without affecting DPP-4- chondrocytes. To assess in vivo therapeutic efficacy of targeting DPP-4+ SnCs, three known senolytics (ABT263, 17DMAG, and metformin) and sitagliptin were comparatively verified in a DMM-induced rat OA model. Sitagliptin treatment specifically and effectively eliminated DPP-4+ SnCs, compared to the other three senolytics. Furthermore, Intra-articular sitagliptin injection to the rat OA model increased collagen type II and proteoglycan expression and physical functions and decreased cartilage destruction, subchondral bone plate thickness and MMP13 expression, leading to the amelioration of OA phenotypes. Collectively, OARSI score was lowest in the sitagliptin treatment group. Taken together, we verified DPP-4 as a surface marker for SnCs and suggested that the selective targeting of DPP-4+ chondrocytes could be a promising strategy to prevent OA progression.

High-glutathione mesenchymal stem cells isolated using the FreSHtracer probe enhance cartilage regeneration in a rabbit chondral defect model.

BACKGROUND: Mesenchymal stem cells (MSCs) are a promising cell source for cartilage regeneration. However, the function of MSC can vary according to cell culture conditions, donor age, and heterogeneity of the MSC population, resulting in unregulated MSC quality control. To overcome these limitations, we previously developed a fluorescent real-time thiol tracer (FreSHtracer) that monitors cellular levels of glutathione (GSH), which are known to be closely associated with stem cell function. In this study, we investigated whether using FreSHtracer could selectively separate high-functioning MSCs based on GSH levels and evaluated the chondrogenic potential of MSCs with high GSH levels to repair cartilage defects in vivo. METHODS: Flow cytometry was conducted on FreSHtracer-loaded MSCs to select cells according to their GSH levels. To determine the function of FreSHtracer-isolated MSCs, mRNA expression, migration, and CFU assays were conducted. The MSCs underwent chondrogenic differentiation, followed by analysis of chondrogenic-related gene expression. For in vivo assessment, MSCs with different cellular GSH levels or cell culture densities were injected in a rabbit chondral defect model, followed by histological analysis of cartilage-regenerated defect sites. RESULTS: FreSHtracer successfully isolated MSCs according to GSH levels. MSCs with high cellular GSH levels showed enhanced MSC function, including stem cell marker mRNA expression, migration, CFU, and oxidant resistance. Regardless of the stem cell tissue source, FreSHtracer selectively isolated MSCs with high GSH levels and high functionality. The in vitro chondrogenic potential was the highest in pellets generated by MSCs with high GSH levels, with increased ECM formation and chondrogenic marker expression. Furthermore, the MSCs' function was dependent on cell culture conditions, with relatively higher cell culture densities resulting in higher GSH levels. In vivo, improved cartilage repair was achieved by articular injection of MSCs with high levels of cellular GSH and MSCs cultured under high-density conditions, as confirmed by Collagen type 2 IHC, Safranin-O staining and O'Driscoll scores showing that more hyaline cartilage was formed on the defects. CONCLUSION: FreSHtracer selectively isolates highly functional MSCs that have enhanced in vitro chondrogenesis and in vivo hyaline cartilage regeneration, which can ultimately overcome the current limitations of MSC therapy.

Comparison of the C-MAC D-blade video laryngoscope and the McCoy laryngoscope for double-lumen endotracheal tube intubation: A prospective randomized controlled study.

BACKGROUND: Inserting a double-lumen endotracheal tube (DLT) poses more challenge than inserting a single-lumen tube. The C-MAC D-blade videolaryngoscope is a useful alternative to the direct laryngoscope. However, no study has compared its performance with that of the McCoy laryngoscope, which has a hyperangulated blade tip similar to that of the C-MAC D-blade. We aimed to compare the performance of the C-MAC D-blade videolaryngoscope with that of the McCoy laryngoscope in DLT intubation. METHODS: In this prospective randomized controlled study, 90 patients requiring DLT intubation were randomly allocated to either the C-MAC D-blade videolaryngoscope group (group C, n = 47) or McCoy laryngoscope group (group M, n = 43). During intubation, the percentage of glottic opening, modified Cormack-Lehane grade, time taken for intubation, malposition of the bronchial lumen, and hemodynamic parameters were recorded. After intubation, we assessed the intubation difficulty scale score and, a postoperative sore throat in the recovery room. RESULTS: The time taken for intubation was 35.85 ±â€…10.77 seconds and 33.18 ±â€…11.97 seconds in groups C and M, respectively (P = .269). The modified Cormack-Lehane grade was significantly lower in group C than in group M (P = .000). Percentage of glottic opening was significantly higher in group C (79.36 ±â€…13.42%) than in group M (53.49 ±â€…29.83%) (P = .000). The intubation difficulty scale score was significantly lower in group C than in group M (P = .030). There were no significant differences between the 2 groups in terms of malposition status, hemodynamic parameters, or visual analog scale score for a postoperative sore throat. CONCLUSION: Although the time taken for intubation was comparable between the 2 intubation devices, the C-MAC D-blade videolaryngoscope facilitated glottis visualization and reduced the intubation difficulty scale better than the McCoy laryngoscope in patients undergoing DLT intubation.

Source Analysis and Effective Control of a COVID-19 Outbreak in a University Teaching Hospital during a Period of Increasing Community Prevalence of COVID-19.

BACKGROUND: South Korea has been experiencing a third wave of coronavirus disease 2019 (COVID-19) since mid-November 2020. Our hospital in Gwangju metropolitan city experienced a healthcare-associated COVID-19 outbreak early in the third wave. The first confirmed COVID-19 patient was a symptomatic neurosurgery resident with high mobility throughout the hospital. We analyzed the transmission routes of nosocomial COVID-19 and discussed infection control strategies. METHODS: We retrospectively analyzed the severe acute respiratory syndrome coronavirus 2 reverse transcription-polymerase chain reaction (RT-PCR) testing results according to time point and evaluated transmission routes. RESULTS: Since COVID-19 was first confirmed in a healthcare worker (HCW) on 11/13/2020, we performed RT-PCR tests for all patients and caregivers and four complete enumeration surveys for all HCWs. We detected three clusters of nosocomial spread and several sporadic cases. The first cluster originated from the community outbreak spot, where an asymptomatic HCW visited, which led to a total of 22 cases. The second cluster, which included patient-to-patient transmission, originated from a COVID-19 positive caregiver before diagnosis and the third cluster involved a radiologist and a banker. We took measures to isolate Building 1 of the hospital for 17 days and controlled the outbreak during a period of increasing community COVID-19 prevalence. Universal screening of all inpatients upon admission and resident caregivers was made mandatory and hospital-related employees are now screened monthly. CONCLUSION: Infection control strategies to prevent the nosocomial transmission of emerging infectious diseases must correspond with community disease prevalence. Our data reinforce the importance of multi-time point surveillance of asymptomatic HCWs and routine surveillance of patients and caregivers during an epidemic.

Cardiac arrest caused by contralateral tension pneumothorax during one-lung ventilation: - A case report.

BACKGROUND: Tension pneumothorax on the contralateral lung during one-lung ventilation (OLV) can be life-threatening if not rapidly diagnosed and managed. However, diagnosis is often delayed because the classic signs of tension pneumothorax are similar to clinical manifestations commonly observed during OLV. CASE: We report a case of contralateral tension pneumothorax in a patient undergoing right upper lobectomy during OLV. The patient suffered from sudden cardiac arrest and was assisted by extra-corporeal membrane oxygenation. CONCLUSIONS: Contralateral pneumothorax during OLV is rare but can occur at any time. Therefore, anesthesiologists should consider this critical complication.

Integrating a Resilience Scorecard and Landscape Performance into a Geodesign Process.

Uncertainty about the impacts of sea level rise make the ability to forecast future spatial conditions a necessary planning/design tool. Geodesign integrates multiple fields of science with change/impact models and planning/design strategies. Proactive planning analyses such as newly developed scorecards allow for plan evaluation; design strategies can now be quantitatively assessed using landscape performance calculators. Neither have been explored as Geodesign tools. A Geodesign process was developed using the resilience scorecard to assess flood vulnerability using projections for the 100 year floodplain with sea level rise by 2100. Projections were used as a guide to develop a resilient master plan for League City, TX, USA. Future impacts of the plan are projected using landscape performance measures.

Comparison of volume-controlled ventilation mode and pressure-controlled ventilation with volume-guaranteed mode in the prone position during lumbar spine surgery.

BACKGROUND: During lumbar spine surgery, patients are placed in the prone position for surgical access. The prone position has various effects on cardiac and pulmonary function, including a decreased cardiac index (CI), decreased dynamic lung compliance (Cdyn), and increased peak inspiratory pressure (Ppeak). In this study, we compared the volume-controlled ventilation mode (VCV) and pressure-controlled ventilation with volume guaranteed mode (PCV-VG) based on hemodynamic and pulmonary variables in the prone position during lumbar spine surgery. METHODS: Thirty-six patients scheduled for lumbar spine surgery in the prone position were enrolled in this prospective, randomized clinical trial. The patients were randomly assigned to receive VCV or PCV-VG. Hemodynamic variables, respiratory variables, and arterial blood gases were measured in the supine position 15 min after the induction of anesthesia, 15 min after placement in the prone position, 30 min after placement in the prone position, and 15 min after placement in the supine position at the end of anesthesia. RESULTS: The hemodynamic variables and arterial blood gas results did not differ significantly between the two groups. Lower Ppeak values were observed in the PCV-VG group than in the VCV group (p = 0.045). The Cdyn values in the VCV group were lower than those in the PCV-VG group (p = 0.040). CONCLUSION: PCV-VG led to lower Ppeak and improved Cdyn values compared with VCV, showing that it may be a favorable alternative mode of mechanical ventilation for patients in the prone position during lumbar spine surgery. TRIAL REGISTRATION: The study was retrospectively registered at ClinicalTrials.gov (NCT03571854). The initial registration date was 6/18/2018.

Salicylideneamino-2-thiophenol modulates nuclear factor-κB through redox regulation during the aging process.

AIM: Many intracellular components have been implicated in the regulation of redox homeostasis, but homeostasis can be unbalanced by reactive species (RS), which also probably contribute to underlying inflammatory processes. Nuclear factor-κB (NF-κB) is a well-known redox-sensitive transcription factor that controls the genes responsible for regulating inflammation. METHODS: In the present study, the authors investigated the effect of short-term salicylideneamino-2-thiophenol (SAL-2) administration on the modulation of pro-inflammatory NF-κB through redox regulation in aged rats. In addition, we compared the effects of SAL-2 and caloric restriction (CR) on inflammation and redox balance. The subjects were 24-month-old (old) Fischer 344 rats administered SAL-2 (10 mg/kg/day) by dietary supplementation or placed on a 30% restricted diet for 10 days, and 6-month-old (young) rats fed ad libitum for 10 days. RESULTS: We found that NF-κB activation and the expressions of its related genes (vascular cell adhesion molecule-1, intercellular adhesion molecule-1, cyclooxygenase-2 and inducible nitric oxide synthase) were suppressed by SAL-2 supplementation in old CR rats to the levels observed in young rats. In addition, our molecular studies showed that the inhibitory effect of SAL-2 on the activation of NF-κB was mediated by the ability of SAL-2 to block the nuclear translocations of cytosolic thioredoxin and redox factor-1. CONCLUSION: These findings strongly indicate that SAL-2 stabilizes age-related redox imbalance and modulates the signal transduction pathway involved in the age-associated molecular inflammatory process.

Modulation of oxidative stress by proanthocyanidin in H2O2-exposed human diploid fibroblast cells.

Proanthocyanidin (a persimmon-peel extract) is known to have potent antioxidative effects, but its protective action specifically against cellular damage has not been fully explored. In this work, we investigated the protective property of proanthocyanidin against cellular oxidative stress with an experimental model, H2O2-exposed human diploid fibroblasts (HDFs). To investigate the proposed underlying beneficial actions of proanthocyanidin as to cellular injury induced by H2O2, several major biochemical parameters were determined, including estimation of total reactive species (RS) generation, antioxidant enzyme activities, reduced glutathione (GSH)/oxidized glulathione (GSSG) ratio, and mitochondrial membrane potential. The results indicate that proanthocyanidin reduced total RS generation while enhancing the activities of catalase and glutathione reductase and the GSH/GSSG ratio. Additionally, proanthocyanidin was found to protect against mitochondrial membrane damage in HDFs treated H2O2. Based on these results, we conclude that proanthocyanidin has strong protective effects against cellular damage to several key cellular functions by suppressing oxidative stress in H2O2-treated HDFs.

Rhamnetin attenuates melanogenesis by suppressing oxidative stress and pro-inflammatory mediators.

Rhamnetin is a naturally occurring polyphenolic compound. In this report, experimental evidence is presented on the suppression of melanogenesis by rhamnetin using B16 murine melanoma cells (B16 cells). To document the underlying anti-melanogenic action of rhamnetin, several key biochemical mediators were quantified: superoxide (O2(•-)), nitric oxide (·NO) and peroxynitrite (ONOO(-)) in vitro, and total reactive species (RS) generation, O2(•-), ·NO and ONOO(-), reduced glutathione (GSH)/GSH-to-oxidized glutathione (GSSG) ratio, prostaglandin E2 (PGE2) and thromboxane B2 (TXB2) in B16 cells. Results revealed that rhamnetin inhibited murine tyrosinase activity, suppressed melanin content and oxidative stress, reducing O2(•-),·NO and ONOO(-) in vitro and total RS generation, O2(•-), ·NO and ONOO(-) in B16 cells, while maintaining a well-balanced GSH/GSSG ratio in B16 cells. Results further revealed that rhamnetin suppressed key pro-inflammatory mediators such as PGE2 and TXB2. Thus, these results strongly indicate that rhamnetin has powerful anti-melanogenic properties through its anti-oxidative and anti-inflammatory actions.

Ginsenoside Rd inhibits the expressions of iNOS and COX-2 by suppressing NF-κB in LPS-stimulated RAW264.7 cells and mouse liver.

Ginsenoside Rd is a primary constituent of the ginseng rhizome and has been shown to participate in the regulation of diabetes and in tumor formation. Reports also show that ginsenoside Rd exerts anti-oxidative effects by activating anti-oxidant enzymes. Treatment with ginsenoside Rd decreased nitric oxide and prostaglandin E2 (PGE2) in lipopolysaccharides (LPS)-challenged RAW264.7 cells and in ICR mouse livers (5 mg/kg LPS; LPS + ginsenoside Rd [2, 10, and 50 mg/kg]). Furthermore, these decreases were associated with the down-regulations of inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 and of nuclear factor (NF)-κB activity in vitro and in vivo. Our results indicate that ginsenoside Rd treatment decreases; 1) nitric oxide production (40% inhibition); 2) PGE2 synthesis (69% to 93% inhibition); 3) NF-κB activity; and 4) the NF-κB-regulated expressions of iNOS and COX-2. Taken together, our results suggest that the anti-inflammatory effects of ginsenoside Rd are due to the down-regulation of NF-κB and the consequent expressional suppressions of iNOS and COX-2.

Hyperin and quercetin modulate oxidative stress-induced melanogenesis.

Hyperin and quercetin are phenolic compounds present in fruits and vegetables that have been reported to possess strong anti-oxidative properties. Although increasing evidence strongly suggests that antioxidants suppress the melanin synthesis that is causally associated with oxidative stress, the protective actions of hyperin and quercetin against oxidative stress-induced melanogenesis have not been fully explored. To elucidate the suppressive effects of hyperin and quercetin on oxidative stress and melanin synthesis, peroxynitrite (ONOO(-)) scavenging activity was measured in vitro as were quantifications of melanin content, intracellular total RS, ONOO(-), superoxide ((•)O(2)), nitric oxide (NO(•)), catalase activity and the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio. Results showed that in vitro, hyperin and quercetin reduced ONOO(-). Additionally, hyperin and quercetin suppressed total RS, ONOO(-), (•)O(2), and NO(•), catalase activity, and melanin synthesis, while they boosted the GSH/GSSG ratio in B16F10 melanoma cells (B16 cells). Therefore, I propose that hyperin and quercetin have a powerful capacity to modulate oxidative stress-induced melanogenesis.

Hypersensitivity reactions to oxaliplatin: clinical features and risk factors in Koreans.

BACKGROUND AND AIM: Oxaliplatin hypersensitivity is a well-known adverse reaction but the prevalence varies and data for frequency and clinical features have not been reported for Korea. Here we evaluates the prevalence and risk factors for hypersensitivity reactions to oxaliplatin after chemotherapy. METHODS: Clinical information on all patients treated with oxaliplatin was retrospectively reviewed in electronic medical records between August 2009 and July 2010 in Seoul National University Bundang Hospital. Patients who experienced hypersensitivity reactions to oxaliplatin were compared with those who did not. RESULTS: A total of 393 patients received oxaliplatin, with 42 (10.7%) experiencing hypersensitivity reactions including three cases of anaphylaxis. Median cycle of the first hypersensitivity reaction was 8. Reactions correlated with lower dexamethasone doses. Other variables were not significant. CONCLUSIONS: The prevalence of hypersensitivity reactions was 10.7%, symptoms being mostly mild and cutaneous. Lower dexamethasone doses could be a predictor for hypersensitivity reactions to oxaliplatin.

Pycnogenol modulates apoptosis by suppressing oxidative stress and inflammation in high glucose-treated renal tubular cells.

Compelling evidence indicates that polyphenolic antioxidants protect against diabetic nephropathy. Pycnogenol is made up of flavonoids, mainly procyanidins and phenolic compounds, and is a known powerful antioxidant. Hyperglycemia is characteristic of diabetic nephropathy and induces renal tubular cell apoptosis. Thus, in this study, we used high glucose-treated renal tubular cells to investigate the protective action of pycnogenol against high glucose-induced apoptosis and diabetic nephropathy. We also sought to further delineate the underlying mechanisms elicited by oxidative stress and inflammation and suppressed by pycnogenol. Results show that pycnogenol significantly suppressed the high glucose-induced morphological changes and the reduction in cell viability associated with cytotoxicity. Bcl2/Bax protein levels indicated pycnogenol's anti-apoptotic effect against high glucose-induced apoptotic cell death. In addition, several key markers of oxidative stress and inflammation were measured for pycnogenol's beneficial effects. Results indicate pycnogenol's anti-oxidative and anti-inflammatory efficacy in suppressing lipid peroxidation, total reactive species (RS), superoxide ((·)O(2)), nitric oxide (NO(·)), peroxynitrite (ONOO(-)), pro-inflammatory inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), and nuclear factor-kappa B (NF-κB) nuclear translocation. Based on these results, we conclude that pycnogenol's anti-oxidative and anti-inflammatory properties underlie its anti-apoptotic effects, suggesting further investigation of pycnogenol as a promising treatment against diabetic nephropathy.

Preparation and characterization of Rh catalyst supported on nanoporous alumina for the ethylene hydroformylation.

Nanoporous gamma-aluminas were prepared by a sol-gel method with and without surfactant, and characterized by nitrogen adsorption-desorption, transmission electron microscopy (TEM), X-ray diffraction (XRD) and temperature programmed reduction (TPR). The resulting materials were applied to Rh catalyst supports for the ethylene hydroformylation. The ordered nanoporous alumina (A-1) which was prepared using surfactant, showed well-developed pore structures with high surface area. Rh catalyst supported on A-1 alumina (Rh/A-1) exhibited higher catalytic activity in the ethylene hydroformylation than other Rh catalysts. It is believed that the high catalytic performance of Rh/A-1 resulted from the well-developed pore structure with high surface area of ordered nanoporous A-1 and consequently finely dispersed Rh particle on the surface of gamma-alumina support.

Attenuation of oxidative stress and inflammation by gravinol in high glucose-exposed renal tubular epithelial cells.

Gravinol, a proanthocyanidin from grape seeds, has polyphenolic properties with powerful anti-oxidative effects. Although, increasing evidence strongly suggests that polyphenolic antioxidants suppress diabetic nephropathy that is causally associated with oxidative stress and inflammation, gravinol's protective action against diabetic nephropathy has not been fully explored to date. In the current study, we investigated the protective action of gravinol against oxidative stress and inflammation using the experimental diabetic nephropathy cell model, high glucose-exposed renal tubular epithelial cells. To elucidate the underlying actions of gravinol, several oxidative and inflammatory markers were estimated. Included are measurements of lipid peroxidation, total reactive species (RS), superoxide (O(2)), nitric oxide (NO), and peroxynitrite (ONOO(-)), as well as nuclear factor-kappa B (NF-kappaB) nuclear translocation. Results indicate that gravinol had a potent inhibitory action against lipid peroxidation, total RS, O(2), NO, ONOO(-), the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio and more importantly, against NF-kappaB nuclear translocation. We propose that gravinol's strong protective effect against high glucose-induced renal tubular epithelial cell damage attenuates diabetic nephropathy by suppressing oxidative stress and inflammation.

Protection against oxidative stress, inflammation, and apoptosis of high-glucose-exposed proximal tubular epithelial cells by astaxanthin.

Astaxanthin is a carotenoid with powerful antioxidant properties that exists naturally in various plants, algae, and seafood. The purpose of the present study is to examine the protective action of astaxanthin against high-glucose-induced oxidative stress, inflammation, and apoptosis in proximal tubular epithelial cells (PTECs). To assess the efficacy of astaxanthin, several key markers and activities were measured, including lipid peroxidation, total reactive species (RS), superoxide (*O(2)), nitric oxide (NO*), and peroxynitrite (ONOO(-)), as well as expressions of inflammatory proteins, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), nuclear factor-kappa B (NF-kappaB) nuclear translocation, and levels of Bcl2/Bax protein. Results showed that astaxanthin effectively suppressed lipid peroxidation, total RS, *O(2), NO*, ONOO(-), iNOS and COX-2 protein levels, NF-kappaB nuclear translocation, and pro-apototic Bax, whereas it increased anti-apoptotic Bcl2 protein levels. On the basis of these findings, it was concluded that in PTECs, astaxanthin has a protective efficacy against several deleterious effects caused by high glucose exposure and proposed that astaxanthin should be explored further as a potential antidiabetic remedy for the treatment of diabetic nephropathy.

BatchGenAna: a batch platform for large-scale genomic analysis of mammalian small RNAs.

UNLABELLED: An increasing number of small RNAs have been discovered in mammals. However, their primary transcripts and upstream regulatory networks remain largely to be determined. Genomic analysis of small RNAs facilitates identification of their primary transcripts, and hence contributes to researches of their upstream regulatory networks. We here report a batch platform, BatchGenAna, which is specifically designed for large-scale genomic analysis of mammalian small RNAs. It can map and annotate for as many as 1000 small RNAs or 10,000 genomic loci of small RNAs at a time. It provides genomic features including RefSeq genes, mRNAs, ESTs and repeat elements in tabular and graphical results. It also allows extracting flanking sequences of submitted queries, specified genomic regions and host transcripts, which facilitates subsequent analysis such as scanning transcription factor binding sites in upstream sequences and poly(A) signals in downstream sequences. Besides small RNA fields, BatchGenAna can also be applied to other research fields, e.g. in silico analysis of target genes of transcription factors. AVAILABILITY: The The platform is freely available at http://biosrv1.bmi.ac.cn/BatchGenAna.

Modulation of oxidative stress and melanogenesis by proanthocyanidins.

Proanthocyanidins (PAs) are polymer chains of flavonoids known to have a high free radical scavenging capacity. However, their efficacy for use in dermatological health has not been fully explored. In the present study, we investigated the inhibitory property of PAs on melanogenesis and oxidative stress of cultured B16F10 melanoma cells (B16 cells) utilizing both oligomer and polymer PAs that were isolated from freshly crushed persimmon peel. To assess the suppressive effects of PAs against oxidative insults, lipid peroxidation, total reactive species (RS), peroxynitrite (ONOO(-)), superoxide ( O(2)), and nitric oxide (NO ) were quantitated. In addition, the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio was measured to evaluate the cellular oxidative status. Results showed that the PAs studied had a strong inhibitory effect on the murine tyrosinase and melanin synthesis that was correlated with the modulation of oxidative stress. Thus, our present work produced evidence that in B16 cells, the anti-melanogenic capacity of PAs as shown by the inhibition of tyrosinase and melanin synthesis likely occurs through the suppression of oxidative stress by the ability of PAs to modulate total RS, O(2), NO , ONOO(-), lipid peroxidation, and redox balance.