Microcatheter-Directed Thrombolysis Using Recombinant Tissue Plasminogen Activator for the Treatment of Acute Superior Mesenteric Artery Embolism: A Case Report.

Background: Acute mesenteric ischemia (AMI) is a life-threatening condition, and in 50% of patients, AMI is caused by acute superior mesenteric artery (SMA) embolism. Endovascular treatment is increasingly being considered the primary modality in selected cases. Many studies have reported that percutaneous aspiration embolectomy using a guiding catheter and thrombolysis with recombinant tissue plasminogen activator (rtPA) are effective in treating SMA embolism. However, no reports on treating SMA embolism using rtPA administered via a microcatheter exist. Case presentation: A 64-year-old man with underlying atrial fibrillation presented with acute SMA embolism revealed using computed tomography (CT). rtPA (total 3 mg) was carefully administered into the occluded SMA through a microcatheter. No complications occurred, and complete revascularization of the SMA was revealed on follow-up CT. Conclusions: Compared with previous reports, this case report reveals that successful revascularization can be achieved using rtPA administered via a microcatheter, with a low dose of rtPA and a short duration of thrombolysis.

Lobar emphysema ratio of more than 1% in the lobe with lung cancer as poor predictor for recurrence and overall survival in patients with stage I non-small cell lung cancer.

BACKGROUND: The purpose of this study was to examine the relationship between the lobar emphysema ratio (LER) and tumor recurrence and survival in patients with stage I non-small cell lung cancer (NSCLC). METHODS: We enrolled 258 patients with surgically proven stage I NSCLC. These patients underwent noncontrast chest CT, and pulmonary lobe segmentation and lobar emphysema quantification were performed using commercially available software. We assessed the LER in the lobe with lung cancer. We divided the patients into two groups according to the LER, and the cut-off value was 1. Furthermore, we analyzed the disease-free survival of high LER and other clinical factors after surgical resection. RESULTS: The 258 patients were divided into two groups: low LER (n = 195) and high LER (n = 63). The right upper lobe was the most frequent location in lung cancer and the most severe location in emphysema. In the Kaplan‒Meier curve, high LER showed a significantly lower disease-free survival (8.21 ± 0.27 years vs 6.53 ± 0.60 years, p = 0.005) and overall survival (9.56 ± 0.15 years vs. 8.51 ± 0.49 years, p = 0.011) than low LER. Stage Ib (2.812 [1.661-4.762], p<0.001) and high LER (2.062 [1.191-3.571], p = 0.010) were poor predictors for disease-free survival in multivariate Cox regression analysis. Stage Ib (4.729 [1.674-13.356], p = 0.003) and high LER (3.346 [1.208-9.269], p = 0.020) were significant predictors for overall survival in multivariate Cox regression analysis. CONCLUSION: A LER of more than 1% in the lobe with lung cancer is a poor predictor for cancer recurrence and overall survival in patients with stage I NSCLC.

Toxicological Assessment of Bromochlorophene: Single and Repeated-Dose 28-Day Oral Toxicity, Genotoxicity, and Dermal Application in Sprague-Dawley Rats.

Bromochlorophene (BCP) has shown good properties in sterilization and antibacterial activity and is widely used as a household chemical. We evaluated the genotoxicity, single and repeated-dose 28-day oral toxicity, and dermal application of a BCP suspension in Sprague-Dawley (SD) rats. For the single-dose toxicity study, a dose of 25-1,000 mg per kg of bodyweight (mg/kg b.w.) of BCP was given once orally to SD rats. Mortality and clinical signs were observed and recorded for the first 30 min after treatment, at 4 h post-administration, and then at least once daily for 14 days after administration. For the repeated-dose 28-day toxicity study, the high dose was set at 1,000 mg/kg b.w. and the middle, middle-low, and low dose were set to 500, 250, and 125 mg/kg, respectively. Hematology and biochemistry parameters were examined. Gross pathologic and histopathologic examinations were performed on selected tissues from all animals. A bacterial reverse mutation assay, in vitro chromosomal aberration assay, and in vivo micronucleus assay were performed to assess genotoxicity-dermal application exposure assessment of BCP in rats. A high oral approximate lethal dose (ALD) of 1,000 mg/kg was observed in the single-dose toxicity test. During the repeated-dose 28-day time period, most animal deaths after administration occurred during the first 3 weeks. The 1,000 mg/kg b.w. oral dose caused the death of six male rats (6/7) and four female rats (4/7). At 500 mg/kg b.w., the female rats showed mortality (1/7). For the biochemistry assays, cholesterol was increased significantly compared to vehicle in both sexes in the 250 and 500 mg/kg groups. Histopathological changes with treatment-related findings were observed in the pancreas in female rats treated with a high dose of BCP compared with the vehicle group. BCP showed no genotoxic effect. These data suggested that the ALD of BCP, estimated as a non-genotoxic substance, was over 1,000 mg/kg b.w. in the single-dose toxicity study, and the NOAEL of BCP was considered to be 250 mg/kg b.w. for male and female rats after repeated oral administration for 28 days under the present study conditions.

Corrigendum: Copper and Cobalt Ions Released From Metal Oxide Nanoparticles Trigger Skin Sensitization.

[This corrects the article DOI: 10.3389/fphar.2021.627781.].

Copper and Cobalt Ions Released from Metal Oxide Nanoparticles Trigger Skin Sensitization.

Human skins are exposed to nanomaterials in everyday life from various sources such as nanomaterial-containing cosmetics, air pollutions, and industrial nanomaterials. Nanomaterials comprising metal haptens raises concerns about the skin sensitization to nanomaterials. In this study, we evaluated the skin sensitization of nanomaterials comparing metal haptens in vivo and in vitro. We selected five metal oxide NPs, containing copper oxide, cobalt monoxide, cobalt oxide, nickel oxide, or titanium oxide, and two types of metal chlorides (CoCl2 and CuCl2), to compare the skin sensitization abilities between NPs and the constituent metals. The materials were applied to KeratinoSensTM cells for imitated skin-environment setting, and luciferase induction and cytotoxicity were evaluated at 48 h post-incubation. In addition, the response of metal oxide NPs was confirmed in lymph node of BALB/C mice via an in vivo method. The results showed that CuO and CoO NPs induce a similar pattern of positive luciferase induction and cytotoxicity compared to the respective metal chlorides; Co3O4, NiO, and TiO2 induced no such response. Collectively, the results implied fast-dissolving metal oxide (CuO and CoO) NPs release their metal ion, inducing skin sensitization. However, further investigations are required to elucidate the mechanism underlying NP-induced skin sensitization. Based on ion chelation data, metal ion release was confirmed as the major "factor" for skin sensitization.

Effects of a complex mixture prepared from agrimonia, houttuynia, licorice, peony, and phellodendron on human skin cells.

Active ingredients derived from natural sources are widely utilized in many industries. Cosmetic active ingredients are largely derived from various plants. In this study, we examined whether a mixture of plant extracts obtained from agrimonia, houttuynia, licorice, peony, and phellodendron (hereafter AHLPP), which are well-known for their effects on skin, could affect skin barrier function, inflammation, and aging in human skin cells. We also determined whether AHLPP extracts sterilized using γ-irradiation (to avoid preservatives) retained their skin cell regulating activity. The AHLPP mixture could downregulate representative pro-inflammatory cytokines including IL 1-ß and IL 7. Procollagen peptide synthesis was also increased by AHLPP treatment along with mRNA upregulation of barrier proteins such as filaggrin and desmoplakin. The AHLPP mixture showed an anti-aging effect by significantly upregulating telomerase activity in human keratinocytes. We further observed TERT upregulation and CDKN1B downregulation, implying a weakening of pro-aging signal transduction. Co-cultivation of a hydrogel polymer containing the AHLPP mixture with human skin cells showed an alteration in skin-significant genes such as FLG, which encodes filaggrin. Thus, the AHLPP mixture with or without γ-irradiation can be utilized for skin protection as it alters the expression of some significant genes in human skin cells.

Prevention of Fine Dust-Induced Vascular Senescence by Humulus lupulus Extract and Its Major Bioactive Compounds.

Both short- and long-term exposure to fine dust (FD) from air pollution has been linked to various cardiovascular diseases (CVDs). Endothelial cell (EC) senescence is an important risk factor for CVDs, and recent evidence suggests that FD-induced premature EC senescence increases oxidative stress levels. Hop plant (Humulus lupulus) is a very rich source of polyphenols known to have nutritional and therapeutic properties, including antioxidant behavior. The aims of this study were to evaluate whether Humulus lupulus extract prevents FD-induced vascular senescence and dysfunction and, if so, to characterize the underlying mechanisms and active components. Porcine coronary arteries and endothelial cells were treated with FD in the presence or absence of hop extract (HOP), and the senescence-associated-beta galactosidase (SA-ß-gal) activity, cell-cycle progression, expression of senescence markers, oxidative stress level, and vascular function were evaluated. Results indicated that HOP inhibited FD-induced SA-ß-gal activity, cell-cycle arrest, and oxidative stress, suggesting that HOP prevents premature induction of senescence by FD. HOP also ameliorated FD-induced vascular dysfunction. Additionally, xanthohumol (XN) and isoxanthohumol (IX) were found to produce the protective effects of HOP. Treatment with HOP and its primary active components XN and IX downregulated the expression of p22phox, p53, and angiotensin type 1 receptor, which all are known FD-induced redox-sensitive EC senescence inducers. Taken together, HOP and its active components protect against FD-induced endothelial senescence most likely via antioxidant activity and may be a potential therapeutic agent for preventing and/or treating air-pollution-associated CVDs.

Universal evaluation of combined standard uncertainty for rotating-element spectroscopic ellipsometers.

We present for the first time a universal expression for the combined standard uncertainty for all types of rotating-element spectroscopic ellipsometers (RE-SEs). Specifically, we introduce general model functions as universal analytic expressions for the combined standard uncertainties of the ellipsometric sample parameters. The model functions are expressed as functions of influencing quantities that are not known exactly. The detailed expressions for the model functions are provided for the common RE-SEs. Our approach can be used for instrumentation, standardization, simulation, metrology, optimization of measurement conditions, and performance comparison between RE-SEs.

Universal evaluations and expressions of measuring uncertainty for rotating-element spectroscopic ellipsometers.

We obtain the universal evaluations and expressions of measuring uncertainty for all types of rotating-element spectroscopic ellipsometers. We introduce a general data-reduction process to represent the universal analytic functions of the combined standard uncertainties of the ellipsometric sample parameters. To solve the incompleteness of the analytic expressions, we formulate the estimated covariance for the Fourier coefficient means extracted from the radiant flux waveform using a new Fourier analysis. Our approach can be used for optimization of measurement conditions, instrumentation, simulation, standardization, laboratory accreditation, and metrology.

Analysis of changes in microRNA expression profiles in response to the troxerutin-mediated antioxidant effect in human dermal papilla cells.

Dermal papilla (DP) cells function as important regulators of the hair growth cycle. The loss of these cells is a primary cause of diseases characterized by hair loss, including alopecia, and evidence has revealed significantly increased levels of reactive oxygen species (ROS) in hair tissue and DP cells in the balding population. In the present study, troxerutin, a flavonoid derivative of rutin, was demonstrated to have a protective effect against H2O2-mediated cellular damage in human DP (HDP) cells. Biochemical assays revealed that pretreatment with troxerutin exerted a protective effect against H2O2-induced loss of cell viability and H2O2-induced cell death. Further experiments confirmed that troxerutin inhibited the H2O2-induced production of ROS and upregulation of senescence-associated ß-galactosidase activity. Using microRNA (miRNA) microarrays, the present study identified 24 miRNAs, which were differentially expressed in the troxerutin-pretreated, H2O2-treated HDP cells. Subsequent prediction using bioinformatics analysis revealed that the altered miRNAs were functionally involved in several cell signaling pathways, including the mitogen-activated protein kinase and WNT pathways. Overall, these results indicated that ROS-mediated cellular damage was inhibited by troxerutin and suggested that the use of troxerutin may be an effective approach in the treatment of alopecia.

LC-APCI-MS/MS Quantification and Topical Bioavailability of Chloroacetamide in Rats.

Chloroacetamide (CAA) is a preservative used in various cosmetic, personal care and household products. Due to the hazard potential for allergic reaction and reproductive toxicity, CAA is being considered a high priority for screening assessment and toxicological re-evaluation. This study describes the development of a highly specific and sensitive atmospheric pressure chemical ionization tandem mass spectrometry method for the determination of CAA in rat plasma and its application to a topical bioavailability study. Chromatographic separations were achieved on a C8 column using a highly aqueous mobile phase with a binary gradient elution. The assay was linear in the concentration range of 5-2,500 ng/mL (r ≥ 0.995) using a small sample volume (100 µL). Applicability of the assay was demonstrated in a bioavailability study in rats after i.v. injection (0.5 or 2 mg/kg) and topical application (7.02 mg/kg). Average elimination half-life and clearance ranged from 26.6 to 30.5 min and 53.9 to 57.3 mL/min/kg, respectively. Upon topical application, CAA was slowly but steadily absorbed for a prolonged time period (12 h). The topical bioavailability was 53.5 and 48.3% for emulsion and lotion, respectively. The developed assay may be useful to examine the relationship between exposure and toxic potential of CAA in risk assessment.

Arctiin blocks hydrogen peroxide-induced senescence and cell death though microRNA expression changes in human dermal papilla cells.

BACKGROUND: Accumulating evidence indicates that reactive oxygen species (ROS) are an important etiological factor for the induction of dermal papilla cell senescence and hair loss, which is also known alopecia. Arctiin is an active lignin isolated from Arctium lappa and has anti-inflammation, anti-microbial, and anti-carcinogenic effects. In the present study, we found that arctiin exerts anti-oxidative effects on human hair dermal papilla cells (HHDPCs). RESULTS: To better understand the mechanism, we analyzed the level of hydrogen peroxide (H2O2)-induced cytotoxicity, cell death, ROS production and senescence after arctiin pretreatment of HHDPCs. The results showed that arctiin pretreatment significantly inhibited the H2O2-induced reduction in cell viability. Moreover, H2O2-induced sub-G1 phase accumulation and G2 cell cycle arrest were also downregulated by arctiin pretreatment. Interestingly, the increase in intracellular ROS mediated by H2O2 was drastically decreased in HHDPCs cultured in the presence of arctiin. This effect was confirmed by senescence associated-beta galactosidase (SA-ß-gal) assay results; we found that arctiin pretreatment impaired H2O2-induced senescence in HHDPCs. Using microRNA (miRNA) microarray and bioinformatic analysis, we showed that this anti-oxidative effect of arctiin in HHDPCs was related with mitogen-activated protein kinase (MAPK) and Wnt signaling pathways. CONCLUSIONS: Taken together, our data suggest that arctiin has a protective effect on ROS-induced cell dysfunction in HHDPCs and may therefore be useful for alopecia prevention and treatment strategies.

Minimally invasive plate osteosynthesis using 3D printing for shaft fractures of clavicles: technical note.

This article describes a minimally invasive plate osteosynthesis technique for midshaft fractures of clavicles using intramedullary indirect reduction and prebent plates with 3D printing models. This technique allows for easy reduction of fractures with accurate prebent plates and minimal soft tissue injury around the fracture site.

Phytosphigosine-1-phosphate increases sensitivity of EGF-dependent cell proliferation.

The dermis is composed of dermal fibroblasts and various synthesized extracellular matrices. Proliferation of these cells is important to skin structure homeostasis. Therefore, human dermal fibroblasts (HDFs) growth factors have been previously evaluated. In the present study, we examined whether phytosphingosine-1-phosphate (PhS1P) regulates gene expression, particularly cell cycle-related genes. In addition, we investigated whether there was a synergistic effect of proliferation induced by PhS1P and epidermal growth factor (EGF) through PhS1P-regulated genes. A microarray approach was utilized to identify gene expression changes in PhS1P-treated HDFs and data were analyzed using gene ontology (GO). In addition, proliferative synergistic effects were measured using an MTT assay. The results showed that PhS1P regulates various genes, particularly cell cycle-related genes. Microarray data, followed by GO, indicated that PhS1P affected the biological processes involved in the cell cycle (cyclins A2, B1 and B2). Furthermore, these genes synergistically affected EGF-dependent proliferation. The results obtained in this study demonstrated that PhS1P altered gene expression profiles, inducing EGF-dependent cell proliferation. Therefore, PhS1p acts as a synergistic effector for EGF.

Arctiin blocks hydrogen peroxide-induced senescence and cell death though microRNA expression changes in human dermal papilla cells

BACKGROUND: Accumulating evidence indicates that reactive oxygen species (ROS) are an important etiological factor for the induction of dermal papilla cell senescence and hair loss, which is also known alopecia. Arctiin is an active lignin isolated from Arctium lappa and has anti-inflammation, anti-microbial, and anti-carcinogenic effects. In the present study, we found that arctiin exerts anti-oxidative effects on human hair dermal papilla cells (HHDPCs). RESULTS: To better understand the mechanism, we analyzed the level of hydrogen peroxide (H2O2)-induced cytotoxicity, cell death, ROS production and senescence after arctiin pretreatment of HHDPCs. The results showed that arctiin pretreatment significantly inhibited the H2O2-induced reduction in cell viability. Moreover, H2O2-induced sub-G1 phase accumulation and G2 cell cycle arrest were also downregulated by arctiin pretreatment. Interestingly, the increase in intracellular ROS mediated by H2O2 was drastically decreased in HHDPCs cultured in the presence of arctiin. This effect was confirmed by senescence associated-beta galactosidase (SA-ß-gal) assay results; we found that arctiin pretreatment impaired H2O2-induced senescence in HHDPCs. Using microRNA (miRNA) microarray and bioinformatic analysis, we showed that this anti-oxidative effect of arctiin in HHDPCs was related with mitogen-activated protein kinase (MAPK) and Wnt signaling pathways. CONCLUSIONS: Taken together, our data suggest that arctiin has a protective effect on ROS-induced cell dysfunction in HHDPCs and may therefore be useful for alopecia prevention and treatment strategies.

Optimizing the precision of a multichannel three-polarizer spectroscopic ellipsometer.

We developed a multichannel three-polarizer spectroscopic ellipsometer based on a data acquisition algorithm for achieving optimized precision. This algorithm measures unnormalized Fourier coefficients accurately and precisely. Offset angles for optical elements were obtained as wavelength-independent values using regression calibration. Derived subsets of data reduction functions were used to calculate sample parameters. Correlation coefficients of Fourier coefficients were used to calculate errors in the sample parameters. Mean standard deviations of the sample parameters for each data reduction method were compared to identify the best method. This approach could be used to identify suitable precision optimization methods for other rotating-element ellipsometers.

In situ control of oxygen vacancies in TiO2 by atomic layer deposition for resistive switching devices.

Oxygen vacancies (V(O)) have profound effects on the physical and chemical performance of devices based on oxide materials. This is particularly true in the case of oxide-based resistive random access memories, in which memory switching operation under an external electrical stimulus is closely associated with the migration and ordering of the oxygen vacancies in the oxide material. In this paper, we report on a reliable approach to in situ control of the oxygen vacancies in TiOx films. Our strategy for tight control of the oxygen vacancy is based on the utilization of plasma-enhanced atomic layer deposition of titanium oxide under precisely regulated decomposition of the precursor molecules (titanium (IV) tetraisopropoxide, Ti[OCH(CH3)2]4) by plasma-activated reactant mixture (N2+O2). From the various spectroscopic and microstructural analyses by using Rutherford backscattering spectrometry, x-ray photoelectron spectroscopy, high-resolution transmission electron microscopy, confocal Raman spectroscopy, and spectroscopic ellipsometry, we found that the precursor decomposition power (R(F)) of plasma-activated reactant mixture determines not only the oxygen vacancy concentration but also the crystallinity of the resulting TiO(x) film: nanocrystalline anatase TiO(x) with fewer oxygen vacancies under high R(F), while amorphous TiOx with more oxygen vacancies under low RF. Enabled by our controlling capability over the oxygen vacancy concentration, we were able to thoroughly elucidate the effect of oxygen vacancies on the resistive switching behavior of TiO(x)-based memory capacitors (Pt/TiO(x)/Pt). The electrical conduction behavior at the high resistance state could be explained within the framework of the trap-controlled space-charge-limited conduction with two characteristic transition voltages. One is the voltage (V(SCL)) for the transition from Ohmic conduction to space-charge-limited conduction, and the other is the voltage (V(TFL)) for transition from space-charge-limited conduction to trap-filled-limited conduction. In this work, we have disclosed for the first time the dependence of these two characteristic transition voltages (i.e., V(SCL) and V(TFL)) on the oxygen vacancy concentration.

Phytosphingosine-1-phosphate represses the hydrogen peroxide-induced activation of c-Jun N-terminal kinase in human dermal fibroblasts through the phosphatidylinositol 3-kinase/Akt pathway.

Dermal fibroblasts are differentiated mesenchymal cells that regulate the extracellular matrix through the production of dermis components. Dermal fibroblasts can be damaged by reactive oxygen species induced by ultraviolet rays and chemicals. In addition to its effects on the dermis, oxidative stress poses a major threat to organisms and is believed to play an essential role in many disease processes. In this study, we show that human dermal fibroblasts (HDFs) express sphingosine-1-phosphate (S1P) receptors S1P(1), S1P(2), and S1P(3). In addition, cell viability of HDFs is increased by phytosphingosine-1-phosphate (PhS1P) via regulation of the Jun N-terminal kinase (JNK)/Akt pathway. Interestingly, regulation of the JNK/Akt pathway by PhS1P attenuated H(2)O(2)-induced cell growth arrest. Together, our data indicate that PhS1P attenuates H(2)O(2)-induced growth arrest through regulation of the signal molecules Akt and JNK, and suggest that PhS1P may have value as an anti-aging material in cosmetics and medicine.