ABSTRACT
Aging (senescence) is an unavoidable biological process that results in visible manifestations in all cutaneous tissues, including scalp skin and hair follicles. Previously, we evaluated the molecular function of adenosine in promoting alopecia treatment in vitro. To elucidate the differences in the molecular mechanisms between minoxidil (MNX) and adenosine, gene expression changes in dermal papilla cells were examined. The androgen receptor (AR) pathway was identified as a candidate target of adenosine for hair growth, and the anti-androgenic activity of adenosine was examined in vitro. In addition, ex vivo examination of human hair follicle organ cultures revealed that adenosine potently elongated the anagen stage. According to the severity of alopecia, the ratio of the two peaks (terminal hair area/vellus hair area) decreased continuously. We further investigated the adenosine hair growth promoting effect in vivo to examine the hair thickness growth effects of topical 5% MNX and the adenosine complex (0.75% adenosine, 1% penthenol, and 2% niacinamide; APN) in vivo. After 4 months of administration, both the MNX and APN group showed significant increases in hair density (MNX + 5.01% (p < 0.01), APN + 6.20% (p < 0.001)) and thickness (MNX + 5.14% (p < 0.001), APN + 10.32% (p < 0.001)). The inhibition of AR signaling via adenosine could have contributed to hair thickness growth. We suggest that the anti-androgenic effect of adenosine, along with the evaluation of hair thickness distribution, could help us to understand hair physiology and to investigate new approaches for drug development.
Subject(s)
Adenosine , Alopecia , Hair Follicle , Hair , Minoxidil , Receptors, Androgen , Signal Transduction , Alopecia/drug therapy , Alopecia/metabolism , Alopecia/pathology , Humans , Male , Receptors, Androgen/metabolism , Adenosine/metabolism , Adenosine/pharmacology , Hair Follicle/drug effects , Hair Follicle/metabolism , Hair Follicle/growth & development , Signal Transduction/drug effects , Minoxidil/pharmacology , Female , Animals , Hair/growth & development , Hair/drug effects , Hair/metabolismABSTRACT
Abnormal inactivation of the Wnt/ß-catenin signaling pathway is involved in skin diseases like androgenetic alopecia, vitiligo and canities, but small-molecule activators are rarely described. In this study, we investigated the stimulatory effects of escin on the canonical Wnt/ß-catenin signaling pathway in cultured human dermal papilla cells (hDPCs). Escin stimulated Wnt/ß-catenin signaling, resulting in increased ß-catenin and lymphoid enhancer-binding factor 1 (LEF1), the accumulation of nuclear ß-catenin and the enhanced expression of Wnt target genes in cultured hDPCs. Escin drastically reduced the protein level of glycogen synthase kinase (GSK)-3ß, a key regulator of the Wnt/ß-catenin signaling pathway, while the presence of the proteasome inhibitor MG-132 fully restored the GSK-3ß protein level. The treatment of secreted frizzled-related proteins (sFRPs) 1 and 2 attenuated the activity of escin in Wnt reporter assays. Our data demonstrate that escin is a natural agonist of the canonical Wnt/ß-catenin signaling pathway and downregulates GSK-3ß protein expression by facilitating the proteasomal degradation of GSK-3ß in cultured hDPCs. Our data suggest that escin likely stimulates Wnt signaling through direct interactions with frizzled receptors. This study underscores the therapeutic potential of escin for Wnt-related diseases such as androgenetic alopecia, vitiligo and canities.
ABSTRACT
INTRODUCTION: This study is to explore the long-term functional outcome of antihypertensive medication-naïve, untreated hypertension (HTN) patients with acute ischemic stroke compared to those with no prior HTN and those with treated HTN. PATIENTS AND METHODS: We analyzed a prospectively collected stroke registry of all patients with acute ischemic stroke consecutively admitted to Incheon St. Mary's Hospital. Patients who received reperfusion therapy were excluded. Long-term functional outcomes were assessed at a 3-month follow-up visit using the modified Rankin Scale. RESULTS: A total of 1044 patients was enrolled. Compared to patients with no or treated HTN, those with untreated HTN had higher odds for more favorable outcomes (adjusted odds ratio (OR): 1.7 [95% CI: 1.0-2.7, p = 0.050*] and 1.7 [95% CI: 1.0-2.8, p = 0.047*], respectively) when the stroke was large vessel atherosclerosis (LAA)/cardioembolic (CE) with large vessel occlusion/stenosis. However, no such association was observed when there was no large vessel occlusion or stenosis, in total patients, or if the index stroke was related to SVO. In untreated HTN patients with LAA/CE and large vessel occlusion/stenosis compared to patients in the lowest mean arterial pressure quartile (< 96.7 mmHg), patients in the second and third highest quartiles had higher odds of favorable outcomes. CONCLUSIONS: Patients with untreated HTN had significantly more favorable outcomes at 3 months after ischemic stroke compared to those with no or treated HTN when the stroke was LAA/CE with large vessel occlusion/stenosis. Untreated HTN patients also showed an association between higher MAP and favorable outcomes.
Subject(s)
Atherosclerosis , Brain Ischemia , Hypertension , Ischemic Stroke , Stroke , Humans , Ischemic Stroke/complications , Brain Ischemia/complications , Brain Ischemia/therapy , Constriction, Pathologic , Stroke/epidemiology , Stroke/therapy , Stroke/complications , Prognosis , Hypertension/complications , Hypertension/epidemiology , Treatment OutcomeABSTRACT
INTRODUCTION: Studies regarding multiple chronic lacunes (MCLs) and clinical outcome according to stroke etiology are scarce. We sought to evaluate the association between MCL and short-term/long-term clinical outcomes according to stroke etiology. PATIENTS AND METHODS: We analyzed a prospectively collected stroke registry of acute ischemic stroke patients over 4 years. The enrolled patients were classified as having large artery atherosclerosis (LAA), small vessel occlusion (SVO), cardioembolic (CE) stroke, and other etiology. The early neurological deterioration (END) and favorable outcome at 3 months were assessed. RESULTS: A total of 1070 patients were enrolled. Patients with MCL had significantly more END compared to those without MCL both in total population (adjusted odds ratio (OR), 1.7; 95% confidence interval [CI], 1.1-2.5; p = 0.013*) and in the LAA group (adjusted OR, 2.3; 95% CI, 1.3-4.2, p < 0.006). Patients with MCL had a significantly lower OR for favorable outcome at 3 months compared to those without MCL both in total population (adjusted OR, 0.7; 95% CI, 0.5-1.0, p = 0.035) and in the LAA group (adjusted OR, 0.6; 95% CI, 0.3-1.0, p = 0.043). However, MCL was not associated with END or long-term functional outcome in patients with SVO, CE, or other etiology. CONCLUSIONS: The presence of MCL was an independent predictive factor for END as well as long-term poor functional outcome in acute ischemic stroke patients. These associations were only observed in patients with LAA, not in those with SVO, CE, or other etiology.
Subject(s)
Atherosclerosis , Brain Ischemia , Ischemic Stroke , Stroke , Humans , Ischemic Stroke/complications , Stroke/epidemiology , Arteries , Brain Ischemia/epidemiology , Risk FactorsABSTRACT
In the present study, we investigated the molecular mechanisms of adenosine for its hair growth promoting effect. Adenosine stimulated the Wnt/ß-catenin pathway by modulating the activity of Gsk3ß in cultured human dermal papilla cells. It also activated adenosine receptor signaling, increasing intracellular cAMP level, and subsequently stimulating the cAMP mediated cellular energy metabolism. The phosphorylation of CREB, mTOR, and GSK3ß was increased. Furthermore, the expression of ß-catenin target genes such as Axin2, Lef1, and growth factors (bFGF, FGF7, IGF-1) was also enhanced. The inhibitor study data conducted in Wnt reporter cells and in cultured human dermal papilla cells demonstrated that adenosine stimulates Wnt/ß-catenin signaling through the activation of the adenosine receptor and Gsk3ß plays a critical role in transmitting the signals from the adenosine receptor to ß-catenin, possibly via the Gαs/cAMP/PKA/mTOR signaling cascade.
Subject(s)
Adenosine , beta Catenin , Adenosine/metabolism , Adenosine/pharmacology , Alopecia/metabolism , Cells, Cultured , Glycogen Synthase Kinase 3 beta/genetics , Glycogen Synthase Kinase 3 beta/metabolism , Hair Follicle/metabolism , Humans , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism , Wnt Signaling Pathway , beta Catenin/genetics , beta Catenin/metabolismABSTRACT
The androgen receptor is a hormone activated transcription factor that regulates the development and maintenance of male characteristics and represents one of the most well-established drug targets, being implicated not only in prostate cancer but also in many non-cancerous human diseases including androgenetic alopecia, acne vulgaris, and hirsutism. In this study, the antiandrogenic effects of FMN were investigated in 22Rv1 and LNCaP prostate cancer cells. FMN inhibited dihydrotestosterone (DHT)-induced protein expression of androgen receptor in 22Rv1cells. In another prostate cancer LNCaP cells, FMN decreased the protein level of DHT-induced prostate specific antigen (PSA). In addition, FMN downregulated DHT-induced mRNA expression of androgen regulated genes in both cell lines, showing less prominent inhibition in 22Rv1cells where androgen receptor had been significantly decreased by FMN. FMN was found to bind androgen receptor, demonstrating that it acted as a competitive androgen receptor antagonist. FMN increased the phosphorylation of Akt in 22Rv1 cells and this increment was abrogated by PI3K inhibitor wortmannin, resulting in a rescued androgen receptor protein level which was decreased by FMN. Additionally, FMN was found to increase the mRNA and protein level of E3 ligase mouse double minute 2. Our data suggest that the androgen receptor signaling is regulated through PI3K-Akt-MDM2 pathway in 22Rv1 cells. Together, our results indicate that FMN facilitated the degradation of androgen receptor in 22Rv1 cells and inhibited the expression of androgen regulated genes by competing the binding of DHT to androgen receptor in LNCaP cells, demonstrating its therapeutic potential as an antiandrogen.
Subject(s)
Flavin MononucleotideABSTRACT
OBJECTIVE: Acute ischemic stroke in the territory of anterior cerebral artery (ACA) is uncommon. Therefore, large population studies evaluating ACA infarction are scarce. We sought to evaluate epidemiological and etiological characteristics of ACA infarction compared to other territorial infarctions. METHODS: We analyzed a prospectively collected stroke registry of all acute ischemic stroke patients for 19 years at two tertiary hospitals. We included patients with acute ischemic stroke caused by large vessel stenosis or occlusion including ACA, middle cerebral artery (MCA), posterior cerebral artery (PCA), and vertebrobasilar artery (VBA). RESULTS: A total of 4171 patients were enrolled. Patients with ACA infarction (N = 288) were significantly older with more females than those with MCA, PCA, or VBA infarction. There were more patients with history of prior ischemic stroke in the ACA infarction group than in other groups. The etiology of the ACA infarction was similar to those of the MCA, PCA and also the total population (66.7-71.8% of LAA and 17.9-20.9% of CE). When patients had prior ischemic stroke history, ACA infarction was more likely to be caused by LAA than MCA or PCA infarction (OR = 6.2, 95% CI 2.0-19.2, p = 0.002 and OR = 4.0, 95% CI 1.1-14.6, p = 0.038, respectively). CONCLUSIONS: Patients with ACA infarction had significantly more prior ischemic stroke than those with MCA, PCA, or VBA infarction. The etiology of ACA infarction in patients with prior ischemic stroke showed significantly more LAA than that of MCA or PCA infarction.
Subject(s)
Infarction, Anterior Cerebral Artery , Infarction, Posterior Cerebral Artery , Ischemic Stroke , Stroke , Anterior Cerebral Artery/diagnostic imaging , Female , Humans , Infarction, Anterior Cerebral Artery/diagnostic imaging , Infarction, Anterior Cerebral Artery/epidemiology , Infarction, Middle Cerebral Artery/complications , Infarction, Posterior Cerebral Artery/complications , Infarction, Posterior Cerebral Artery/diagnostic imaging , Infarction, Posterior Cerebral Artery/epidemiology , Stroke/complicationsABSTRACT
This article proposes a neural-network-based adaptive asynchronous event-triggered design strategy for the distributed consensus tracking of uncertain lower triangular nonlinear multi-agent systems under a directed network. Compared with the existing event-triggered recursive consensus tracking designs using multiple neural networks for each follower and continuous communications among followers, the primary contribution of this study is the development of an asynchronous event-triggered consensus tracking methodology based on a single-neural network for each follower under event-driven intermittent communications among followers. To this end, a distributed event-triggered estimator using neighbors' triggered output information is developed to estimate a leader signal. Subsequently, the estimated leader signal is used to design local trackers. Only a triggering law and a single-neural network are used to design the local tracking law of each follower, irrespective of unmatched unknown nonlinearities. The information of each follower and its neighbors is asynchronously and intermittently communicated through a directed network. Thus, the proposed asynchronous event-triggered tracking scheme can save communicational and computational resources. From the Lyapunov stability theorem, the stability of the entire closed-loop system is analyzed and the comparative simulation results demonstrate the effectiveness of the proposed control strategy.
ABSTRACT
This study investigates a quantized feedback design problem for distributed adaptive leader-following consensus of uncertain strict-feedback nonlinear multiagent systems with state quantizers. It is assumed that all system nonlinearities of followers are unknown and heterogeneous, all state variables of each follower are quantized by a uniform state quantizer, and quantized states of followers are only communicated under a directed network. Compared with previous approximation-based distributed consensus tracking methods for uncertain lower triangular multiagent systems, the main contribution of this article is addressing the distributed quantized state communication problem in the adaptive leader-following consensus tracking field of uncertain lower triangular multiagent systems. A quantized-states-based local adaptive control law for each follower is derived by designing quantized-signals-based weight tuning laws for neural-network-based function approximators. By analyzing the boundedness of the local quantization errors, it is shown that the total closed-loop signals are uniformly ultimately bounded and the consensus tracking errors converge to a sufficiently small domain around the origin. Finally, simulation examples, including multiple ship steering systems, are considered to verify the effectiveness of the proposed theoretical approach.
Subject(s)
Neural Networks, Computer , Nonlinear Dynamics , Algorithms , Consensus , FeedbackABSTRACT
Dexpanthenol (D-panthenol) is a precursor of vitamin B5 (pantothenic acid) and is widely used for dietary supplements and topical applications. D-panthenol has long been used in hair care products for the purpose of anti-hair loss, its effects and the underlying mechanisms, however, were barely reported. In this study, the effects of D-panthenol on human hair follicle cells, including dermal papilla cells (hDPCs) and outer root sheath cells (hORSCs), were investigated. D-panthenol enhanced the cell viability, increasing the cellular proliferation marker Ki67 in cultured hDPCs. The markers for apoptosis (Caspase3/9) and cell senescence (p21/p16), reported to be expressed in aged or resting phase follicles, were significantly reduced by D-panthenol. Anagen-inducing factors (ALP; ß-catenin; versican), which trigger or elongate the anagen phase, were stimulated by D-panthenol. On the other hand, D-panthenol reduced TGF-ß1 expressions in both mRNA and protein levels. The expression of VEGF, which is important for peripheral blood vessel activation; was up-regulated by D-panthenol treatment. In cultured hORSCs, cell proliferation and viability were enhanced, while the mRNA expression of cell senescence markers (p21/p16) was significantly down-regulated. The expressions of both VEGF and its receptor (VEGFR) were up-regulated by D-panthenol. In conclusion, our data suggest that the hair growth stimulating activity of D-panthenol was exerted by increasing the cell viability, suppressing the apoptotic markers, and elongating the anagen phase in hair follicles.
Subject(s)
Apoptosis/drug effects , Cellular Senescence/drug effects , Hair Follicle/cytology , Pantothenic Acid/analogs & derivatives , Antigens, Surface/genetics , Antigens, Surface/metabolism , Apoptosis/genetics , Biomarkers , Cell Proliferation/drug effects , Cells, Cultured , Cellular Senescence/genetics , Gene Expression , Gene Expression Regulation/drug effects , Hair Follicle/drug effects , Hair Follicle/metabolism , Humans , Pantothenic Acid/pharmacology , RNA, Messenger , Vitamin B Complex/pharmacologyABSTRACT
PURPOSE: An increasing number of people are suffering from hair loss disorders. Niacinamide has long been used as an active ingredient for anti-hair loss preparations but the exact mechanism has not been clearly elucidated yet. The effects of niacinamide were investigated in cultured human dermal papilla cells (hDPCs). METHODS: To investigate the anti-hair loss effect of niacinamide and its molecular mechanisms, Western blot analysis, ELISA, quantitative RT-PCR and immunocytochemistry were performed. To study the protective effects of niacinamide against H2O2-induced oxidative stress, ROS generation and cytotoxicity were evaluated by DCF-DA assay and LDH release assay, respectively. Minoxidil was used as a positive control. RESULTS: Niacinamide decreased the protein expression level of DKK-1 which promotes regression of hair follicles by inducing catagen. The protein expression levels of cell senescence markers, p21 (CDKN1A) and p16 (CDKN2A) which are related to cell cycle arrest, were decreased. The expression of versican was increased by niacinamide treatment in cultured hDPCs. We have found that niacinamide decreased the H2O2-induced intracellular ROS production in cultured hDPCs. Moreover, niacinamide decreased the protein expression levels of H2O2-induced p21 and p16 and diminished the secretion of H2O2-induced DKK-1. CONCLUSION: Our data demonstrate that niacinamide could enhance hair growth by preventing oxidative stress-induced cell senescence and premature catagen entry of hair follicles.
ABSTRACT
Objective: Insomnia and depression are prevalent disorders that often co-occur. This study aimed to investigate the impact of clinically significant insomnia symptoms on the prevalence and clinical presentation of clinically significant depressive symptoms and vice versa. Methods: This study used data from the Korean Headache-Sleep Study (KHSS), a nationwide cross-sectional population-based survey regarding headache and sleep. Clinically significant insomnia symptoms were defined as Insomnia Severity Index (ISI) scores ≥ 10 and clinically significant depressive symptoms were defined as Patient Health Questionnaire-9 (PHQ-9) scores ≥ 10, respectively. We referred clinically significant insomnia symptoms and clinically significant depressive symptoms as insomnia symptoms and depressive symptoms, respectively. Results: Of 2,695 participants, 290 (10.8%) and 116 (4.3%) were classified as having insomnia and depressive symptoms, respectively. The prevalence of depressive symptoms was higher among participants with insomnia symptoms than in those without insomnia symptoms (25.9 vs. 1.7%, respectively, P < 0.001). Among participants with depressive symptoms, the PHQ-9 scores were not significantly different between participants with and without insomnia symptoms (P = 0.124). The prevalence of insomnia symptoms was significantly higher among participants with depressive symptoms than in those without depressive symptoms (64.7 vs. 8.3%, respectively, P < 0.001). The ISI scores were significantly higher among participants with insomnia and depressive symptoms than in participants with insomnia symptoms alone (P < 0.001). Conclusions: Participants with depressive symptoms had a higher risk of insomnia symptoms than did those without depressive symptoms. The severity of depressive symptoms did not significantly differ based on insomnia symptoms among participants with depressive symptoms; however, the severity of insomnia symptoms was significantly higher in participants with depressive symptoms than in those without depressive symptoms.
ABSTRACT
Adenosine is a cellular metabolite with diverse derivatives that possesses a wide range of physiological roles. We investigated the molecular mechanisms of adenosine and cordycepin for their promoting effects in wound-healing process. The mitochondrial energy metabolism and cell proliferation markers, cAMP responsive element binding protein 1 (CREB1) and Ki67, were enhanced by adenosine and cordycepin in cultured dermal fibroblasts. Adenosine and cordycepin stimulated adenosine receptor signaling via elevated cAMP. The phosphorylation of mitogen-activated protein kinase kinase (MEK) 1/2, mammalian target of rapamycin (mTOR) and glycogen synthase kinase 3 beta (Gsk3b) and Wnt target genes such as bone morphogenetic protein (BMP) 2/4 and lymphoid enhancer binding factor (Lef) 1 were activated. The enhanced gene expression by adenosine and cordycepin was abrogated by adenosine A2A and A2B receptor inhibitors, ZM241385 and PSH603, and protein kinase A (PKA) inhibitor H89, indicating the involvement of adenosine receptor A2A, A2B and PKA. As a result of Wnt/ß-catenin pathway activation, the secretion of growth factors such as insulin-like growth factor (IGF)-1 and transforming growth factor beta (TGFß) 3 was increased, previously reported to facilitate the wound healing process. In addition, in vitro fibroblast migration was also increased, demonstrating their possible roles in facilitating the wound healing process. In conclusion, our data strongly demonstrate that adenosine and cordycepin stimulate the Wnt/ß-catenin signaling through the activation of adenosine receptor, possibly promoting the tissue remodeling process and suggest their therapeutic potential for treating skin wounds.
Subject(s)
Adenosine/pharmacology , Deoxyadenosines/pharmacology , Fibroblasts/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , Receptor, Adenosine A2A/metabolism , Receptor, Adenosine A2B/metabolism , Wnt Signaling Pathway/drug effects , Cell Line , Fibroblasts/pathology , Humans , Skin/injuries , Skin/metabolism , Skin/pathology , Wound Healing/drug effects , beta Catenin/metabolismABSTRACT
The present study aimed to investigate the molecular mechanism of quercitrin, a major constituent of Hottuynia cordata extract, for its hair growth stimulating activities in cultured human dermal papilla cells (hDPCs). Quercitrin enhanced the cell viability and cellular energy metabolism in cultured hDPCs by stimulating the production of NAD(P)H and mitochondrial membrane potential (ΔΨ). The expression of Bcl2, an essential marker for anagen hair follicle and cell survival, was increased by quercitrin treatment. Quercitrin also increased the cell proliferation marker Ki67. The expression of growth factors-such as bFGF, KGF, PDGF-AA, and VEGF-were increased by quercitrin both in mRNA and protein levels. In addition, quercitrin was found to increase the phosphorylation of Akt, Erk, and CREB in cultured hDPCs, while inhibitors of MAPKs reversed the effects of quercitrin. Finally, quercitrin stimulated hair shaft growth in cultured human hair follicles. Our data obtained from present study are in line with those previously reported and demonstrate that quercitrin is (one of) the active compound(s) of Hottuynia cordata extract which showed hair growth promoting effects. It is strongly suggested that the hair growth stimulating activity of quercitrin was exerted by enhancing the cellular energy metabolism, increasing the production of growth factors via activation of MAPK/CREB signaling pathway.
Subject(s)
Cyclic AMP Response Element-Binding Protein/metabolism , Hair/growth & development , Intercellular Signaling Peptides and Proteins/metabolism , MAP Kinase Signaling System , Quercetin/analogs & derivatives , Apoptosis/drug effects , Butadienes/pharmacology , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Dermis/cytology , Energy Metabolism/drug effects , Extracellular Signal-Regulated MAP Kinases/metabolism , Gene Expression Regulation/drug effects , Hair/drug effects , Humans , Intercellular Signaling Peptides and Proteins/genetics , MAP Kinase Signaling System/drug effects , Nitriles/pharmacology , Phosphorylation/drug effects , Proto-Oncogene Proteins c-akt/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Quercetin/chemistry , Quercetin/pharmacology , RNA, Messenger/genetics , RNA, Messenger/metabolism , Receptors, Cell Surface/genetics , Receptors, Cell Surface/metabolismABSTRACT
A decentralized adaptive quantized feedback tracking problem is addressed for uncertain interconnected nonlinear systems in a strict-feedback form. All local state variables for each subsystem are quantized by a hysteresis quantizer. Different from the existing results in the literature, the primary contribution of this study is to establish an adaptive control design and stability analysis strategy using the local quantized state variables in the decentralized tracking field. A novel recursive design approach is presented to deal with unmatched interconnections and nonlinearities in the quantized feedback control framework, without any restrictions on virtual control laws. The total closed-loop stability is analyzed by deriving some technical lemmas on the boundedness of quantization error signals.
ABSTRACT
BACKGROUND: Dermal papilla cells (DPCs) play a key role in hair growth among the various cell types in hair follicles. Especially, DPCs determine the fate of hair follicle such as anagen to telogen transition and play a pivotal role in androgenic alopecia (AGA). This study was performed to elucidate the hair growth promoting effects of Polygonum multiflorum extract (PM extract) in cultured human DPCs and its underlying mechanisms. METHODS: The effects of PM extract on cultured DPCs were investigated. Cell viability and mitochondrial activity were measured by CCK-8 and JC-1 analysis, respectively. Western blotting, dot blotting, ELISA analysis, immunocytochemistry and real-time PCR analysis were also performed to elucidate the changes in protein and mRNA levels induced by PM extract. 3D cultured DPC spheroids were constructed for mimicking the in vivo DPs. The hair growth stimulatory effect of PM extract was evaluated using human hair follicle organ culture model. RESULTS: PM extract increased the viability and mitochondrial activity in cultured human DPCs in a dose dependent manner. The expression of Bcl2, an anti-apoptotic protein expressed dominantly in anagen was significantly increased and that of BAD, a pro-apoptotic protein expressed in early catagen was decreased by PM extract in cultured DPCs and/or 3D DPC spheroid culture. PM extract also decreased the expression of catagen inducing protein, Dkk-1. Growth factors including IGFBP2, PDGF and VEGF were increased by PM extract, revealed by dot blot protein analysis. We also have found that PM extract could reverse the androgenic effects of dihydrotestosterone (DHT), the most potent androgen. Finally, PM extract prolonged the anagen of human hair follicles by inhibiting catagen entry in human hair follicle organ culture model. CONCLUSION: Our data strongly suggest that PM extract could promote hair growth by elongating the anagen and/or delaying the catagen induction of hair follicles through activation of DPCs.
Subject(s)
Androgens/metabolism , Fallopia multiflora , Hair Follicle/drug effects , Plant Extracts/pharmacology , Cells, Cultured , Dose-Response Relationship, Drug , Hair/growth & development , Humans , Organ Culture Techniques , Republic of KoreaABSTRACT
BACKGROUND: Early consciousness recovery after cardiac arrest (CA) is one of the most explicit and self-evident prognostic factors for clinical outcomes. We aimed to evaluate the prognostic value of electroencephalography (EEG) phenotypes according to the American Clinical Neurophysiology Society's Critical Care EEG classification for predicting early recovery after CA. METHODS: Consecutive patients admitted to the ICU after CA were enrolled. We analyzed Glasgow Coma Scale (GCS) score within 10 days after CA and evaluated mortality within 28 days according to EEG pattern subtype. RESULTS: Among the total of 71 patients, 9 had periodic discharges (PDs) EEG pattern, 4 had rhythmic delta activity (RDA), 8 had spike-and-wave (SW), 22 had low voltage, 5 had burst suppression, and 23 had other EEG patterns. Initial GCS scores, GCS scores 3 days after CA (or 3 days after targeted temperature management [TTM]), and 10 days after CA (or 10 days after TTM) were significantly different among EEG subtypes (p < 0.001, respectively) (Table 2). GCS scores were significantly higher in RDA and the other EEG group compared to the PDs, SW, low voltage, and burst suppression groups (p < 0.001). Significant group × time interactions were observed for the follow-up period between EEG phenotypes (p < 0.001) demonstrating the most increase in the other EEG pattern group. CONCLUSIONS: Consciousness states were significantly worse in the PDs, SW, burst suppression, and low-voltage groups compared to the RDA and the other EEG pattern within 10 days after CA. The degree of consciousness recovery differed significantly by EEG pattern subtype within 10 days.
Subject(s)
Consciousness/physiology , Electroencephalography/methods , Heart Arrest/diagnosis , Heart Arrest/physiopathology , Adult , Aged , Aged, 80 and over , Cohort Studies , Electroencephalography/trends , Female , Humans , Male , Middle Aged , Predictive Value of Tests , Time Factors , Treatment OutcomeABSTRACT
In this study, we investigated the role and mechanism of imperatorin (IMP) in chronic inflammation and airway remodeling. The levels of TNF-α, IL-1ß, IL-6, IL-8, VEGF, α-SMA, and ROS were detected by ELISA, immunohistochemistry (IHC), immunofluorescence, and Western blot. In addition, we evaluated the effect of IMP on MAPK, PI3K/Akt, NF-κB, and Nrf2/HO-1 signaling pathways. IMP treatment obviously attenuated the production of inflammatory cytokines and inflammatory cells in bronchoalveolar lavage ï¬uid of OVA-induced airway remodeling model. Meanwhile, it significantly inhibited inflammatory cell infiltration, goblet cell hyperplasia, collagen deposition, VEGF production, α-SMA, and ROS expression. Our study has shown that IMP could regulate the signaling pathways including MAPK, PI3K/Akt, NF-κB, and Nrf2/HO-1 to release the inflammatory responses. IMP might attenuate airway remodeling by the down-regulation of Nrf2/HO-1/ROS/PI3K/Akt, Nrf2/HO-1/ROS/MAPK, and Nrf2/HO-1/ROS/NF-κB signaling pathways.
Subject(s)
Airway Remodeling/drug effects , Asthma/metabolism , Furocoumarins/pharmacology , Heme Oxygenase-1/metabolism , Membrane Proteins/metabolism , NF-E2-Related Factor 2/metabolism , Reactive Oxygen Species/metabolism , Signal Transduction/drug effects , Animals , Asthma/chemically induced , Asthma/drug therapy , Cell Line , Cytokines/metabolism , Disease Models, Animal , Female , Furocoumarins/therapeutic use , Mice , Mice, Inbred BALB C , Myocytes, Smooth Muscle/metabolism , Ovalbumin/pharmacologyABSTRACT
STUDY OBJECTIVES: Insomnia is the most common sleep disorder with significant psychiatric/physical comorbidities in the general population. The aim of this study is to investigate whether socioeconomic and demographic factors are associated with gender differences in insomnia and subtypes in Korean population. METHOD: The present study used data from the nationwide, cross-sectional study on sleep among all Koreans aged 19 to 69 years. The Insomnia Severity Index (ISI) was used to classify insomnia symptoms and their subtypes (cutoff value: 9.5). The Pittsburgh Sleep Quality Index (PSQI), Goldberg Anxiety Scale (GAS) and Patient Health Questionnaire-9 (PHQ-9) were used to measure sleep quality, anxiety and depression. RESULTS: A total of 2695 participants completed the survey. The overall prevalence of insomnia symptoms was 10.7%, including difficulty in initiating sleep (DIS) (6.8%), difficulty in maintaining sleep (DMS) (6.5%) and early morning awakening (EMA) (6.5%), and these symptoms were more prevalent in women than in men. Multivariate analysis showed that female gender, shorter sleep time and psychiatric complications were found to be independent predictors for insomnia symptoms and subtypes. After adjusting for covariates among these factors, female gender remained a significant risk factor for insomnia symptoms and their subtypes. As for men, low income was related to insomnia. CONCLUSION: Approximately one-tenth of the sample from the Korean general population had insomnia symptoms. The prevalence of insomnia symptom and the subtypes were more prevalent in women than men. Gender is an independent factor for insomnia symptoms.
Subject(s)
Anxiety/epidemiology , Depression/epidemiology , Sleep Initiation and Maintenance Disorders/epidemiology , Adult , Aged , Comorbidity , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Prevalence , Republic of Korea/epidemiology , Risk Factors , Sex Factors , Sleep , Socioeconomic Factors , Surveys and Questionnaires , Young AdultABSTRACT
BACKGROUND: Antiepileptic drug (AED) induced dyskinesia is an unusual manifestation in the medical field. In the previous case reports describing first generation-AED related involuntary movements, the authors suggested that a plausible cause is pharmacokinetic interactions between two or more AEDs. To date, development of dyskinesia after levetiracetam (LEV) has not been reported. CASE PRESENTATION: A 28-year-old woman with a history of brain metastasis from spinal cord glioblastoma presented with several generalized tonic-clonic seizures without restored consciousness. LEV was administered intravenously. Thereafter no more clinical or electroencephalographic seizures were noted on video-EEG monitoring, while chorea movement was observed in her face and bilateral upper limbs. DISCUSSION AND CONCLUSIONS: To our knowledge, there is no case report of dyskinesia after administration of LEV. Considering the temporal relationship and absence of ictal video-EEG findings, we suggest that development of choreoathetosis was closely associated with the undesirable effects of LEV. We propose that dopaminergic system dysregulation and genetic susceptibility might underlie this unusual phenomenon after LEV treatment.