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Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer, caused by mutagenesis resulting from excess ultraviolet radiation or other types of oxidative stress. These stressors also upregulate production of a cutaneous innate immune element, cathelicidin antimicrobial peptide (CAMP), via endoplasmic reticulum (ER) stress-initiated, sphingosine-1-phosphate (S1P) signaling pathway. While CAMP has beneficial antimicrobial activities, it also can be pro-inflammatory and pro-carcinogenic. We addressed whether and how S1P-induced CAMP production leads to cSCC development. Our study demonstrated that: 1) CAMP expression is increased in cSCC cells and skin from cSCC patients; 2) S1P levels are elevated in cSCC cells, while inhibition of S1P production attenuates CAMP-stimulated cSCC growth; 3) exogenous CAMP stimulates cSCC, but not normal human keratinocyte growth; 4) blockade of formyl peptide receptor-like (FPRL) 1 protein, a CAMP receptor, attenuates cSCC growth as well as the growth and invasion of cSCC cells mediated by CAMP into an extracellular matrix-containing fibroblast substrate; 5) Foxp3+ regulatory T cell (which decreases anti-tumor immunity) levels increase in cSCC skin; and 6) CAMP induces ER stress in cSCC cells. Together, the ER stress-S1P-CAMP axis forms a vicious circle, creating a favorable environment for cSCC development, i.e., cSCC growth and invasion impedes anti-cancer immunity.
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Asarum chungbuensis, a species endemic to Korea, has a limited distribution across the Korean Peninsula and is used in traditional medicine. Despite its importance, the genome structure, genetic composition, and phylogenetic relationships based on its chloroplast genome have not been documented. In this study, the complete chloroplast genome of A. chungbuensis was newly assembled. The chloroplast genome is 190,179 base pairs (bp) long, and the overall GC content (%) of the plastid was 36.8%. The chloroplast genome size of A. chungbuensis is longer than that of the normal chloroplast genome (160 kb) because of an inverted small single-copy (SSC) duplication that incorporates the SSC into an inverted repeat (IR) region. By extension, this duplication event causes this chloroplast genome to lack an SSC, unlike other formal structures. The chloroplast genome, with a tripartite structure, consisted of a single-copy region of 93,351 bp with a 34.6% GC content and two IR regions, each with a length of 48,414 bp and a 38.8% GC content. Additionally, it was found to have 113 genes, including 79 PCG genes, 30 tRNA genes, and four rRNA genes. Phylogenetic analysis revealed that A. chungbuensis was grouped with A. heterotropoides var. seoulense, which diverged from the clade comprising A. koreanum and A. patens. The newly sequenced A. chungbuensis chloroplast genome could provide valuable genomic information for determining unique genome structures, especially for the assessment of genetic diversity, phylogenetic relationships, species conservation, and biogeographic studies of the genus Asarum.
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INTRODUCTION: Diesel particulate matter (DPM) emitted from diesel engines is a major source of air pollutants. DPM is composed of elemental carbon, which adsorbs organic compounds including toxic polycyclic aromatic hydrocarbons (PAHs). The skin, as well as airways, is directly exposed to DPM, and association of atopic dermatitis, psoriasis flares, and premature skin aging with air pollutant levels has been documented. In skin, the permeation of DPM and DPM-adsorbed compounds is primarily blocked by the epidermal permeability barrier deployed in the stratum corneum. Depending upon the integrity of this barrier, certain amounts of DPM and DPM-adsorbed compounds can permeate into the skin. However, this permeation into human skin has not been completely elucidated. METHODS: We assessed the permeation of PAHs (adsorbed to DPM) into skin using ex vivo normal (barrier-competent) organ-cultured human skin after application of DPM. Two major PAHs, 2-methylnaphthalene and triphenylene, and a carcinogenic PAH, benzo(a)pyrene, all found in DPM, were measured in the epidermis and dermis using liquid chromatography electrospray ionization tandem mass spectrometry. In addition, we investigated whether a topical formulation can attenuate the permeation of DPM into skin. RESULTS: 2-Methylnaphthalene, triphenylene, and benzo(a)pyrene were recovered from the epidermis. Although these PAHs were also detected in the dermis after DPM application, these PAH levels were significantly lower than those found in the epidermis. We also demonstrated that a topical formulation that has the ability to form more uniform membrane structures can significantly suppress the permeation of PAHs adsorbed to DPM into the skin. CONCLUSION: Toxic compounds adsorbed by DPM can permeate even barrier-competent skin. Hence, barrier-compromised skin, such as in atopic dermatitis, psoriasis, and xerosis, is even more vulnerable to air pollutants. A properly formulated topical mixture that forms certain membrane structures on the skin surface can effectively prevent permeation of exogenous substances, including DPM, into skin.
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Eremurus zoae Vved. 1971 is a perennial herbaceous plant in the family Asphodelaceae and an endemic species of the Kyrgyz Republic; however, its complete chloroplast genome sequence has not been reported. Here, we investigated the complete chloroplast (cp) genome of E. zoae using next-generation sequencing. The cp genome was 153,744 bp long, with a large single copy (84,020 bp), a small single copy (16,766 bp), and a pair of inverted repeats (26,479 bp). The genome encodes 132 genes, including 86 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. Phylogenetic analysis revealed that the genus Eremurus forms a monophyletic group and E. zoae is closely related to E. chinensis. This study provides a molecular foundation for future phylogenetic studies of Eremurus.
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OBJECTIVES: Accumulating evidence suggests that physical activity (PA) is an efficient intervention to maintain functional capabilities and mitigate physiological changes in the older population. However, an attempt has yet to be made to comprehensively investigate the published landscape on the subject. METHODS: This study had two aims. The first aim was to perform a bibliometric analysis for two keywords, "aging" and "PA", to analyze the research trend. Since "frailty" was the most noticeable co-occurring keyword with the two keywords, the second aim was to investigate the effects of PA, particularly, resistance training (RT), on frailty using a meta-analysis to provide a summary of the current evidence base. RESULTS: The bibliometric analysis revealed that the number of publications on this research topic has gradually increased, highlighting the importance of understanding the role of PA in aging. The meta-analysis found that RT had significant beneficial effects on physical frailty factors, including handgrip strength, lower limb strength, balance, gait speed, and stair-climbing ability. CONCLUSION: These findings demonstrate that RT is an effective intervention for improving physical function in frail populations; thus, it has important implications for the development of PA programs for older adults with frailty. Future research is warranted to explore the optimal dose, frequency, and duration of RT programs for older adults, as well as the potential benefits of combining RT with other forms of PA, such as aerobic or balance exercises.
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Xerosis is a common sign of both type 1 and type 2 diabetes mellitus (DM), and patients with DM and mouse models for DM show a compromised epidermal permeability barrier. Barrier defects then allow the entry of foreign substances into the skin, triggering inflammation, infection, and worsening skin symptoms. Characterizing how barrier abnormalities develop in DM could suggest treatments for xerosis and other skin disease traits. Because the proper ratio, as well as proper bulk amounts, of heterogeneous ceramide species are keys to forming a competent barrier, we investigated how ceramide metabolism is affected in type 1 DM using a mouse model (induced by streptozotocin). Chronic inflammation, evident in the skin of mice with DM, leads to (i) decreased de novo ceramide production through serine racemase activation-mediated attenuation of serine palmitoyl transferase activity by D-serine; (ii) changes in ceramide synthase activities and expression that modify the ratio of ceramide molecular species; and (iii) increased ceramide-1-phosphate, a proinflammatory lipid mediator, that stimulates inflammatory cytokine expression (TNFα and IFN-γ). Together, chronic inflammation affects ceramide metabolism, which attenuates epidermal permeability barrier formation, and ceramide-1-phosphate could amplify this inflammation. Alleviation of chronic inflammation is a credible approach for normalizing barrier function and ameliorating diverse skin abnormalities in DM.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Humanos , Ceramidas , Inflamação/metabolismo , Serina , FosfatosRESUMO
INTRODUCTION: The outermost layer of the skin, the epidermis, is directly exposed to external stress (e.g., irradiation, allergens, and chemicals). Changes in epidermal conditions/environment in response to this stress could also influence conditions of the dermis, located directly beneath the epidermis. Yet, whether/how any epidermal environment changes in response to external stress affect dermal functions has not been completely clarified. METHODS: We employed ultraviolet irradiation B (UVB) (which hardly reaches the dermis) as a model of external stress. Human keratinocytes and human dermal fibroblasts were treated with UVB and conditioned medium of keratinocytes exposed to UVB (UVB-keratinocyte-M), respectively. We assessed (1) inflammatory cytokines and lipid mediators in keratinocytes; (2) matrix metalloprotease (MMP) levels and collagen degradation in fibroblasts; (3) ex vivo organ-cultured human skin was treated with UVB. MMP levels and collagen degradation were examined; (4) test whether the mixture of agent (agent cocktail) consisting of dihydroceramide, niacin amide, resveratrol, glucosyl hesperidin, and phytosterol ester that has been shown to improve skin barrier integrity can mitigate influence of UVB in skin; and (5) a pilot one-arm human clinical test to assess efficacy of formulation containing agent cocktail on stratum corneum hydration, skin elasticity, and wrinkle index. RESULTS: Inflammatory-cytokine and -lipid mediator production were increased in cultured keratinocytes treated with UVB, while matrix MMP-1, -3, and -9 production and collagen degradation were increased in fibroblasts incubated with UVB-keratinocyte-M. mRNA expression of COL1A1 (that codes type 1 collagen) levels was decreased in fibroblasts incubated with UVB-keratinocyte-M. The study using ex vivo organ-cultured human skin showed both MMP-1 and MMP-9 expression were increased in both epidermis and dermis and increased dermal collagen degradation following UVB irradiation. Increased MMP production and collagen degradation were attenuated by application of an agent cocktail. Finally, a pilot clinical study demonstrated that the formulation containing our agent cocktail likely has the ability to improve skin hydration, increase skin elasticity, and reduce the appearance of wrinkles. CONCLUSION: Epidermal changes in epidermal environment and conditions in response to external stress affect dermal conditions, and these negative effects of external stress on various skin layers can be pharmacologically mitigated.
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Metaloproteinase 1 da Matriz , Envelhecimento da Pele , Humanos , Metaloproteinase 1 da Matriz/genética , Metaloproteinase 1 da Matriz/metabolismo , Derme/metabolismo , Epiderme/metabolismo , Colágeno Tipo I , Citocinas/metabolismo , Lipídeos , Raios Ultravioleta , FibroblastosRESUMO
As unmanned aerial vehicles have become popular, the number of accidents caused by an operator's inattention have increased. To prevent such accidents, the operator should maintain an attention status. However, limited research has been conducted on the brain-computer interface (BCI)-based system with an alerting module for the operator's attention recovery of unmanned aerial vehicles. Therefore, we introduce a detection and alerting system that prevents an unmanned aerial vehicle operator from falling into inattention status by using the operator's electroencephalogram signal. The proposed system consists of the following three components: a signal processing module, which collects and preprocesses an electroencephalogram signal of an operator, an inattention detection module, which determines whether an inattention status occurred based on the preprocessed signal, and, lastly, an alert providing module that presents stimulus to an operator when inattention is detected. As a result of evaluating the performance with a real-world dataset, it was shown that the proposed system successfully contributed to the recovery of operator attention in the evaluating dataset, although statistical significance could not be established due to the small number of subjects.
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Eletroencefalografia , Processamento de Sinais Assistido por Computador , Cognição , HumanosRESUMO
The safety of children has always been an important issue, and several studies have been conducted to determine the stress state of a child to ensure the safety. Audio signals and biological signals including heart rate are known to be effective for stress state detection. However, collecting those data requires specialized equipment, which is not appropriate for the constant monitoring of children, and advanced data analysis is required for accurate detection. In this regard, we propose a stress state detection framework which utilizes both audio signal and heart rate collected from wearable devices, and adopted machine learning methods for the detection. Experiments using real-world data were conducted to compare detection performances across various machine learning methods and noise levels of audio signal. Adopting the proposed framework in the real-world will contribute to the enhancement of child safety.
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Dispositivos Eletrônicos Vestíveis , Criança , Frequência Cardíaca , Humanos , Aprendizado de Máquina , Estresse FisiológicoRESUMO
With the advance of military technology, the number of unmanned combat aerial vehicles (UCAVs) has rapidly increased. However, it has been reported that the accident rate of UCAVs is much higher than that of manned combat aerial vehicles. One of the main reasons for the high accident rate of UCAVs is the hypovigilance problem which refers to the decrease in vigilance levels of UCAV operators while maneuvering. In this paper, we propose hypovigilance detection models for UCAV operators based on EEG signal to minimize the number of occurrences of hypovigilance. To enable detection, we have applied hidden Markov models (HMMs), two of which are used to indicate the operators' dual states, normal vigilance and hypovigilance, and, for each operator, the HMMs are trained as a detection model. To evaluate the efficacy and effectiveness of the proposed models, we conducted two experiments on the real-world data obtained by using EEG-signal acquisition devices, and they yielded satisfactory results. By utilizing the proposed detection models, the problem of hypovigilance of UCAV operators and the problem of high accident rate of UCAVs can be addressed.