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Background A heterogeneous radiological response is frequently observed in cancer patients and could reflect tumor heterogeneity. We investigated the prognostic impact of heterogeneous radiological responses in patients with advanced non‐small‐cell lung cancer (NSCLC) who received platinum‐based chemotherapy. Methods The treatment response according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria was evaluated in 212 patients with advanced NSCLC who received platinum‐based chemotherapy. Patients with partial response (PR) or stable disease (SD) were classified into “PR homo,” “PR hetero,” “SD homo,” and “SD hetero” by the presence of a heterogeneous radiological response, and survival was compared between groups. We also compared survival based on the presence of metabolic responses in lesions with heterogeneous radiological responses. Results Fifty‐two patients (24.5%) were classified as PR, 112 patients (52.8%) as SD, and 48 patients (22.7%) as progressive disease (PD). There was no significant difference in progression‐free survival (PFS) and overall survival (OS) between the PR homo and PR hetero groups. The SD homo group had a longer PFS and OS than the SD hetero group. In the SD hetero group, patients with increased maximum standardized uptake value (SUVmax) in lesions with heterogeneous radiological responses had a shorter PFS than those with a stable SUVmax. Conclusions The presence of lesions with radiological heterogeneity was associated with disease progression and poor prognosis in the SD group. Patients with heterogeneous radiological responses require careful monitoring., Patients with heterogeneous radiological responses in the SD group had a shorter PFS and OS. In particular, patients with increased SUVmax in lesions with heterogeneous radiological responses had a shorter PFS than patients with a stable SUVmax. The presence of lesions with radiological heterogeneity was associated with disease progression and poor prognosis in the SD group.

In a laser-plasma electron acceleration, the quality of electron beams is sensitive to the parameters of a laser and a plasma density. With a given laser, higher plasma density may be good for higher charge, while lower density is better for longer acceleration channel, generating higher peak energy at the expense of charge. The dependence of electron beam parameters on the plasma density is, therefore, crucial to find the operating condition for applications. After the target chamber is evacuated, the plasma density and the focal position of the laser beam in the plasma channel can be remotely controlled during the experiments. The plasma density can be obtained by extracting the phase information from captured interferogram, followed by numerically computing the integral derived using Abel inversion. We suggested the simple idea of FFT Filtering and Reconstructing (FR), to be processed prior to a typical computing process, which is the continuous wavelet transform (CWT) for phase shift and the Fourier–Hankel transform (FH) for the integral of Abel inversion here. The FFT filtering can suppress the errors due to the noise, while the reconstructing can select the different data points between the fringes to reduce the systematic error and improve the visibility in interferograms. We confirm the FR-CWT-FH method can provide the average plasma density in uniform region and the longitudinal channel structure with high accuracy, letting the in-situ monitoring possible. The fringe spacing in reconstruction and the wavelet frequency in CWT can be selected differently depending on the shape of plasma density, such as uniform or rising (or falling), and its length of each region to obtain the detailed structure of plasmas.

Altered energy metabolism has been implicated both in aging and the pathogenesis of late-onset Alzheimer’s disease (LOAD). However, it is unclear which anomalies are acquired phenotypes and which are inherent and predispose to disease. We report that neural progenitor cells and astrocytes differentiated from LOAD patient-derived induced pluripotent stem cells exhibit multiple inter-related bioenergetic alterations including: changes in energy production by mitochondrial respiration versus glycolysis, as a consequence of alterations in bioenergetic substrate processing and transfer of reducing agents, reduced levels of NAD/NADH, diminished glucose uptake and response rates to insulin (INS)/IGF-1 signaling, decreased INS receptor and glucose transporter 1 densities, and changes in the metabolic transcriptome. Our data confirm that LOAD is a “multi-hit” disorder and provide evidence for innate inefficient cellular energy management in LOAD that likely predisposes to neurodegenerative disease with age. These processes may guide the development and testing of diagnostic procedures or therapeutic agents.

The redox co-factor nicotinamide adenine dinucleotide (NAD) declines with age, and NAD deficits are specifically associated with dysfunctional energy metabolism in late-onset Alzheimer's disease (LOAD). Nicotinamide riboside (NR), a dietary NAD precursor, has been suggested to ameliorate the aging process or neurodegeneration. We assessed whether NR with or without caffeine, which increases nicotinamide mononucleotide transferase subtype 2 (NMNAT2), an essential enzyme in NAD production, modulates bioenergetic functions in LOAD. In LOAD patients-and young or old control individuals-derived dermal fibroblasts as well as in induced pluripotent stem cell-differentiated neural progenitors and astrocytes, NR and caffeine cell type-specifically increased the NAD pool, transiently enhanced mitochondrial respiration or glycolysis and altered the expression of genes in the NAD synthesis or consumption pathways. However, continued treatment led to reversed bioenergetic effects. Importantly, NR and caffeine did not alter the characteristics of a previously documented inherent LOAD-associated bioenergetic phenotype. Thus, although NR and caffeine can partially restore diminished NAD availability, increasing NAD alone may not be sufficient to boost or restore energy metabolism in brain aging or alter aberrant energy management in LOAD. Nicotinamide riboside might still be of value in combination with other agents in preventive or therapeutic intervention strategies to address the aging process or age-associated dementia.

The major sites of metastasis in non-small cell lung cancer (NSCLC) are bones, the brain, adrenal glands, the liver, the contralateral lung, and distant lymph nodes. Solitary metastasis in an uncommon site is very rare; therefore, it has not often been reported. Identifying whether a solitary lesion is a metastatic lesion is important because it decisively influences the stage and treatment decisions. We report a series of cases of NSCLC diagnosis with uncommon solitary metastasis. (1) A 71-year-old man was diagnosed with poorly differentiated NSCLC after a bronchoscopic biopsy of a tumor in the bronchus of the right middle lobe. A hypermetabolic lesion was observed in the tail of the pancreas using positron emission tomography/computed tomography (PET/CT), and metastasis of NSCLC was confirmed using endoscopic ultrasound fine-needle aspiration (EUS-FNA). (2) A 77-year-old man was diagnosed with squamous cell carcinoma after a bronchoscopic biopsy of a tumor in the bronchus of the left upper lobe. A hypermetabolic lesion was observed in the bilateral lobes of the thyroid gland using PET/CT, and metastasis of the squamous cell carcinoma was confirmed by FNA and cytology. (3) A 79-year-old woman was diagnosed with adenocarcinoma by brushing cytology performed on the apicoposterior segmental bronchus of the left upper lobe. Hypermetabolic lesions were observed using PET/CT in the subcutaneous layer of the right back and the left breast, and metastases of adenocarcinoma were confirmed by biopsies in each lesion. These three patients were treated with platinum-based chemotherapy for stage IV lung cancer. With this case series, we recommend that, when a solitary lesion is observed in NSCLC patients, a tissue biopsy should be performed, even if the lesion is located in an organ where lung cancer metastasis is uncommon.

The cumulative results indicate that the neutrophil to lymphocyte ratio of peripheral blood (pbNLR) is a useful prognostic factor in patients with various cancers. In contrast to peripheral blood, the bronchoalveolar lavage (BAL) fluid is in direct contact with the lung lesion. However, no study has reported on the clinical utility of the NLR of BAL fluid (bNLR) for patients with lung cancer. To investigate the clinical utility of the bNLR as a prognostic factor in patients with lung cancer, we conducted a retrospective review of the prospectively collected data. A total of 45 patients were classified into high bNLR (n = 29) and low bNLR (n = 16) groups. A high pbNLR and high bNLR were associated with a shorter overall survival (p < 0.001 and p = 0.011, respectively). A multivariable analysis confirmed that ECOG PS (p = 0.023), M stage (p = 0.035), pbNLR (p = 0.008), and bNLR (p = 0.0160) were independent predictors of overall survival. Similar to the pbNLR, a high bNLR value was associated with a poor prognosis in patients with lung cancer. Although further studies are required to apply our results clinically, this is the first study to show the clinical value of the bNLR in patients with lung cancer.

Background Defects of the nasal ala and tip have a complex three-dimensional structure that makes them challenging to reconstruct. Many reconstructive options have been described for nasal ala and tip defects, ranging from primary closure to local flaps and skin grafts. However, it is difficult to determine which method will yield the best cosmetic results in each individual case. Thus, the purpose of this study was to determine which surgical procedures for reconstructing defects of the nasal ala and tip have better cosmetic results. Methods From 2008 to 2018, 111 patients underwent surgery to reconstruct skin defects after resection of skin cancer in the nasal ala or tip. Their charts were reviewed to obtain data on age, sex, surgical location, size of the defect, surgical method, and cosmetic results using a visual analog scale (VAS). Results For nasal ala reconstruction, the most commonly used surgical technique was the nasolabial flap (n= 42). This method also had the highest VAS score (7/10). The most commonly selected surgical method for nasal tip reconstruction was the bilobed flap (n= 13), and bilobed flaps and primary closure had the highest VAS score (7/10). Conclusion Nasolabial flaps showed excellent cosmetic results for the reconstruction of nasal ala defects, while primary closure and bilobed flaps yielded excellent cosmetic results for the reconstruction of nasal tip defects.

Circulating tumor DNA (ctDNA) has been utilized to monitor the clinical course of patients of non-small-cell lung cancer (NSCLC) who receive therapies targeting druggable mutations. However, despite providing valuable information on how NSCLC would naturally progress, the clinical utility of ctDNA for clinical-course monitoring and prediction of treatment-naïve NSCLC patients without druggable mutations remain unknown. We longitudinally followed a total of 12 treatment-naïve NSCLC patients, who did not harbor EGFR and ALK mutations, by collecting clinical information, radiological data, and plasma samples. Changes in ctDNA levels and tumor burden (TB) were compared with each other. New metastasis development, volume doubling time (VDT), and overall survival (OS) were analyzed regarding ctDNA detection at diagnosis. ctDNA was detected in the plasma of seven (58.3%) patients. Changes in ctDNA levels correlated with those in TB in a substantial fraction (57.1%) of patients and was also associated with brain metastasis, tumor necrosis, or pneumonia in other patients. All patients with ctDNA detection developed new metastasis during follow-ups in the organs that had been devoid of metastasis at diagnosis. The patients without ctDNA detection did not develop new metastasis (median duration of follow-ups: 9.8 months). In addition, patients with ctDNA detection had shorter VDT (p = 0.039) and worse OS (p = 0.019) than those without ctDNA detection. The natural course of NSCLC progression can be monitored by measuring ctDNA levels. Detection of ctDNA at diagnosis can predict development of new metastasis, rapid tumor growth and poor survival of NSCLC patients.

BACKGROUND Closed reduction is the standard treatment for nasal bone fractures, which are the most common type of facial bone fractures. We investigated the effect of closed reduction on quality of life. METHODS The 15-dimensional health-related quality of life survey was administered to 120 patients who underwent closed reduction under general anesthesia for nasal bone fractures from February 2018 to December 2019, on both the day after surgery and 3 months after surgery. Three months postoperatively, the presence or absence of five nasal symptoms (nose obstruction, snoring, pain, nasal secretions, and aesthetic dissatisfaction) was also evaluated. RESULTS The quality of life items that showed significant changes between immediately after surgery and 3 months postoperatively were breathing, sleeping, speech, excretion, and discomfort. Low scores were found at 3 months for breathing, sleeping, and distress. There were 31 patients (25.83%) with nose obstruction, 25 (20.83%) with snoring, 12 (10.00%), with pain, 11 (9.17%) with nasal secretions, and 29 (24.17%) with aesthetic dissatisfaction. CONCLUSION Closed reduction affected patients' quality of life, although most aspects improved significantly after 3 months. However, it was not possible to rule out deterioration of quality of life due to complications and dissatisfaction after surgery.

Hypoxia-inducible factor-1α (HIF-1α) has been reported to be up-regulated in psoriatic epidermis, resulting in increased proliferation and abnormal differentiation of human keratinocytes (KCs). However, the role of HIF-1α in psoriatic epidermis, which is mainly composed of KCs, is poorly understood. Here, we show that morphogenic protein 6 (BMP6) is down-regulated when HIF-1α is upregulated in patients with psoriasis skin lesions. HIF-1α overexpression in primary human KCs promoted proliferation and inhibited terminal differentiation. Furthermore, HIF1-α repressed the expression of BMP6 by binding directly to the hypoxia-response element (HRE) in the BMP6 promotor region, which shows that BMP6 is a novel target gene of HIF-1α. We also found that HIF-1α-mediated BMP6 suppression could alter the proliferation status by modulating the expression levels of cell cycle regulatory proteins and also affect the early differentiation of KCs. Therefore, we suggest that HIF-1α-dependent BMP6 suppression has a critical role in the induction of hyper-proliferation and abnormal differentiation in psoriatic KCs.

Background Tight junctions (TJs) have important roles in skin barrier function. The TJ protein claudin-1 (CLDN1) is decreased in atopic dermatitis (AD). However, little is known about the mechanism of CLDN1 down-expression. Objective To elucidate the effect of IL-33 on CLDN1 expression in keratinocytes. Methods Normal human epidermal keratinocytes (NHEKs) and human skin equivalent models (HSEMs) were cultured in vitro in the presence of IL-33. Production of CLDN1, signal transducer and activator of transcription 3 (STAT3) and Mitogen-activated protein kinases (MAPK) expression were measured by real-time PCR, western blot and immunofluorescence assay. MAPK inhibitors and small interfering RNA were used to confirm the signal pathway of STAT3 and CLDN1. Barrier function was measured by transepithelial electric resistance (TEER) and FITC-dextran flux assays. Electrophoretic Mobility Shift Assay was used to detect STAT3 transcriptional activity. Results Levels of CLDN1 expression were reduced in the epidermis of AD-model mice overexpressing IL-33. IL-33 down-regulated the expression of CLDN1 mRNA and protein in NHEKs and HSEMs. IL-33 attenuated transepithelial electric resistance and induced FITC-dextran flux in NHEKs. The IL-33 suppressed CLDN1 expression was regulated by an extracellular signal-regulated kinase (ERK) and signal transducer and activator of transcription 3 (STAT3). STAT3 suppressed CLDN1 expression by direct binding to the promoters. Conclusion IL-33 may down-regulate CLDN1 expression through the ERK/STAT3 pathway in keratinocytes.

Purpose: The aim of this study was to compare the complications of flap surgery in non-smokers and smokers and to determine how the incidence of complications was affected by the abstinence period from smoking before and after flap surgery. Methods: In PubMed and Scopus, terms “smoking” and “flap survival” were used, which resulted in 113 papers and 65 papers, respectively. After excluding 6 duplicate titles, 172 titles were reviewed. Among them, 45 abstracts were excluded, 20 full papers were reviewed, and finally 15 papers were analyzed. Results: Post-operative complications such as flap necrosis ( P < .001), hematoma ( P < .001), and fat necrosis ( P = .003) occurred significantly more frequently in smokers than in non-smokers. The flap loss rate was significantly higher in smokers who were abstinent for 24 hours post-operatively than in non-smokers (n = 1464, odds ratio [OR] = 4.885, 95% confidence interval [CI] = 2.071-11.524, P < .001). The flap loss rate was significantly lower in smokers who were abstinent for 1 week post-operatively than in those who were abstinent for 24 hours post-operatively (n = 131, OR = 0.252, 95% CI = 0.074-0.851, P = .027). No significant difference in flap loss was found between non-smokers and smokers who were abstinent for 1 week preoperatively (n = 1519, OR = 1.229, 95% CI = 0.482-3.134, P = .666) or for 4 weeks preoperatively (n = 1576, OR = 1.902, 95% CI = 0.383-2.119, P = .812). Conclusion: Since smoking decreases the alveolar oxygen pressure and subcutaneous wound tissue oxygen, and nicotine causes vasoconstriction, smokers are more likely to experience flap loss, hematoma, or fat necrosis than non-smokers. Preoperative and post-operative abstinence period of at least 1 week is necessary for smokers who undergo flap operations.

The transient behavior of the fuel cladding of a sodium-cooled fast reactor (SFR) is one of the main design issues concerning the safety of a reactor. The safety margin of the cladding during transient events has been widely studied in the past. However, previously, the transient testing was conducted using as-received specimens (and not aged specimens). For ensuring safety margin of the fuel rod of an SFR, the effect of aging on the transient behavior of the fuel cladding should be considered. This study examines this effect on the transient behavior of HT9 cladding by correlating between the UTS and the result of the ramp test and proposes a modified Dorn parameter that reflects the aging effect. At 100 MPa of the hoop stress, the modified Dorn parameter, which reflects an aging effect, is 7.7266 × 10 −14 and the Dorn parameter of as-received specimen is 1.749 × 10 −12 . This results in the enhanced safety during transient event by considering aging effect.

Volatile organic compounds (VOCs) are major air pollutants known to have adverse effects on skin. Many reports have shown an association between air pollutants and skin aging. However, there is no report on VOCs association with skin aging. The aim of this study is to identify the biologic effects of VOCs on fibroblasts. We investigated the effects of chloroform on cysteine-rich 61 (CYR61) expression in human skin fibroblasts using western blot and reverse transcriptionpolymerase chain reaction. We also observed the change of type I procollagen and matrix metalloproteinase after exposure to chloroform using western blot. We explored the involvement of early growth response-1 (Egr-1) using siRNA s in the fibroblasts. Chloroform exposure increased the expression of CYR61 protein and mRNA level. Elevated CYR61 downregulates type I procollagen and upregulates MMP-1. Egr-1 overexpression upregulates CYR61 promoter activity. CYR61 promoter activity was lower in Egr-1 siRNA-transfected fibroblasts. The present study demonstrates that CYR61 is transcriptionally regulated by chloroform exposure through transcription factor Egr-1, and alters collagen homeostasis in human skin fibroblasts.

Volatile organic compounds (VOCs) can be an important environmental risk factor in the development and/or aggravation of atopic dermatitis (AD). In a several studies to evaluate the clinical effects of air pollution including VOCs on skin symptoms in AD patients. Although these accumulated data shows an association between exposure to VOCs and aggravation of AD, the molecular effects of VOCs on the aggravation of AD is still not clear. The present study demonstrates increases of thymic stromal lymphopoietin (TSLP) in keratinocytes following exposure to toluene. We further investigated the regulatory mechanisms of toluene-induced TSLP expression in human keratinocytes. Toluene induces early growth response-1 (Egr-1) protein expression in human keratinocytes. Moreover, treatment of Egr-1 siRNA abolished toluene-induced TSLP protein expression. Taken together, these findings suggest that in human keratinocytes, the up-regulation of TSLP by toluene is induced through an Egr-1 dependent mechanism.

Background Skin defects of head and neck need reconstruction using various local flaps. In some cases, surgeons should consider skin graft for large skin defect. It is important to heal skin graft and donor sites. The authors investigated wound healing mechanisms at the donor sites with split-thick-ness skin graft (STSG). In this study, the authors compared two types of immediate regraft including sheets and islands for the donor site after facial skin graft using remnant skin. Methods The author reviewed 10 patients who underwent STSG, from March 2015 to May 2017, for skin defects in the craniofacial area. The donor site was immediately covered with the two types using remnant skin after harvesting skin onto the recipient site. Depending on the size of the remnant skin, we conducted regraft with the single sheet (n= 5) and island types (n= 5). Results On postoperative day 1 and 3 months, the scar formation was evaluated using the Patient and Observer Scar Assessment Scale (POSAS) and Vancouver Scar Scale (VSS). Total POSAS and VSS scores for the island type were lower than in single sheet group after 3 months postoperatively. There was significant difference in specific categories of POSAS and VSS. Conclusion This study showed a reduction in scar formation following immediate regrafting of the remnant skin at the donor site after STSG surgery. Particularly, the island type is useful for clinical application to facilitate healing of donor sites with STSG.

A laser-induced intense Ka hard X-ray source was developed by using a novel copper film target and a 27-TW femtosecond laser system. A specially designed pinhole camera was employed to measure the X-ray photon flux, X-ray energy spectrum, and X-ray source image. By adapting a single photon counting method, we estimated the photon number in the full width at half maximum (FWHM) spectral region to be 1.74 × 109 photons/sr for 8.05-keV Cu Ka X-rays. The shape of the X-ray source was matched well with that of the focused laser beam on the target. By provision of a lengthy copper film of 50 m with a thickness of 50 µm, the novel copper film target is capable of long time operation of more than 27 hours at a repetition rate of 10 Hz. The hard X-ray source is suitable for applications in single-shot X-ray contrast imaging or in ultrafast pump-probe analyses of material structures.

Atopic dermatitis (AD) is a chronic inflammatory skin disease in which T-helper type 2 (Th2)-type immune responses are dominant. Th2 cytokine, interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP) have been suggested to have an important role in AD. IL-33 is highly expressed in AD, but its role in AD has not yet been fully understood. To further identify the role of IL-33 in AD, we investigated the expression of TSLP induced by IL-33 in keratinocytes. This study revealed that IL-33 induced TSLP expression in human keratinocytes. Early growth response protein 1 (Egr)-1, which is an inflammatory transcriptional factor, is induced by IL-33. IL-33-mediated TSLP induction in keratinocytes was suppressed by treatment with mitogen-activated protein kinase (MAPK) inhibitors or small interfering RNA against Egr-1. Chromatin immunoprecipitation (ChIP) assay indicated the direct involvement of Egr-1 in IL-33-mediated TSLP induction. Taken together, these findings indicate that IL-33 may increase TSLP expression through an Egr-1-dependent mechanism via ERK1/2, JNK and p38 activation in keratinocytes. These data suggest that the IL-33-ERK/JNK/p38/Egr-1/TSLP axis is involved in allergic skin Th2 inflammation, and it may be a novel therapeutic target.

Purpose: Gigantomastia is associated with several physical symptoms. Reduction mammaplasty can resolve discomfort, but an objective and quantitative analysis of the symptomatic relief associated with reduction mammaplasty is limited. Therefore, we evaluated the efficacy of reduction mammaplasty, as measured by the symptomatic relief using objective indicators. Methods: Between January and May 2009, patients who visited our clinic for gigantomastia were retrospectively evaluated, for neck, shoulder, and back pain. Fifteen subjects were enrolled in this study; they all underwent treatment by reduction mammaplasty, and presented neck and shoulder pain. The surface body temperature was measured at the cervical and thoracic areas, by infrared thermography (Iris-5000; Medicore, Seongnam, Korea). Infrared thermography was re-assessed in nine of 15 cases who returned for follow-up examinations 3 to 4 months after surgery. Results: The mean age of the group was 40.6±10.3 years; the mean body mass index was 24.6±2.1 kg/m. The average weight of the removed breast tissue after surgery was 616±241.8 g on the right, and 603±259.6 g on the left. On pre-, and post-operative infrared thermography, the average absolute value of the thoracic and cervical surface temperatures changed siginificantly (p

The receptor-interacting protein kinase 4 (RIP4), a serine/threonine kinase, is an important modulator of epidermal growth and cutaneous inflammation. We found that RIP4 expression was significantly increased in the lesional skin of psoriasis. However, the role and regulatory mechanism of RIP4 in psoriasis have not been characterized. After treatment with IL-17, RIP4 mRNA and protein levels were increased in HaCaT cells. IL-17 also activated the RIP4 promoter. To understand the functional role of RIP4 in keratinocyte and to investigate the genes regulated by RIP4, RNA-based microarray analysis was performed. Among immune response-related genes, CCL20 expression was significantly changed by RIP4. To identify RIP4-interacting protein, an immunoprecipitation assay was performed. As a result, STAT3 was identified as a new protein that interacts with RIP4. The interaction of RIP4 and STAT3 enhanced STAT3 phosphorylation. In addition, the transcriptional activity of STAT3 induced by RIP4 regulated IL-17-mediated CCL20 expression in HaCaT cells. Taken together, these findings indicate that IL-17 increased RIP4-mediated STAT3 phosphorylation by directly interacting with STAT3. Thus, transcriptional activation of STAT3 promotes the expression of CCL20. Thus, activations of these signalling pathways by RIP4 may contribute to epithermal inflammation in psoriatic keratinocytes.

Quantum dots (QDs) have shown great potential for biomedical use in a broad range including diagnostic agents. However, the regulatory mechanism of dermal toxicity is poorly understood. In this study, we investigated how QDs-induced apoptosis is regulated in human keratinocytes. We also examined the effect of carboxylic acid-coated QDs (QD 565 and QD 655) on reactive oxygen species (ROS) production and apoptosis-related cellular signalling. The viability of keratinocyte was inhibited by two types of QDs in a concentration-dependent manner. QDs induce ROS production and blockade of AKT phosphorylation. Moreover, the cleavage of AKT-dependent pro-apoptotic proteins such as poly (ADP-ribose) polymerase, caspases-3 and caspases-9 was significantly increased. We also found that a decrease in cellular ROS level by ROS scavenger, N-acetylcysteine (NAC), resulting in the abolishment of QDs-induced AKT de-phosphorylation and cellular apoptosis. Interestingly, QD 655 had a more cytotoxic effect including oxidative stress and AKT-dependent apoptosis than QD 565. In addition, QD 655 had the cytotoxic potential in the human skin equivalent model (HSEM). These data show that QD-induced intracellular ROS levels may be an important parameter in QD-induced apoptosis. These findings from this study indicate that intracellular ROS levels might determine the apoptotic potential of keratinocyte by QD via blockade of AKT phosphorylation.

Zinc Oxide nanoparticles (ZnO NPs) in its small size with large reactive surfaces can lead to toxicological injury by generating reactive oxygen species (ROS) and oxidative stress. Recently, ZnO NPs were shown to play a role in acute or chronic toxicities with mammalian cells, where its mechanism of toxicity is not fully characterized yet. In this study, the potential mechanisms of ZnO NPs in inducing and increasing oxidative stress for causing cellular apoptosis were investigated with human keratinocytes. Indeed, ZnO NPs induced significant intracellular ROS and mitochondrial ROS productions. And it seemed that cellular ROS levels induced by ZnO NPs led to the dissipation of the mitochondrial membrane potentials and elicited the cellular apoptosis. The induced ROS production by ZnO NPs was blocked with chelator treatment, which inhibited the ZnO ion. The present study demonstrates that increased levels of ROS by ZnO NPs cause mitochondrial dysfunction and cellular apoptosis.