RESUMEN
Aconitum coreanum (A. coreanum), a traditional Chinese medicine, has been proved to treat ischemic stroke (IS). However, the mechanisms of A. coreanum's anti-stroke is currently unknown. This study aimed to uncover the effect and mechanisms of A. coreanum. And study raw Aconitum coreanum (RA) and steamed Aconitum coreanum (SA) and Aconitum coreanum processed with ginger and Alumen (GA) on the mechanism of the pharmacological action of treating IS. Determining whether the efficacy is affected after processing. The right unilateral ligation of the carotid artery of gerbils was used to mimic IS. The neurological function score, infarct volume, oxidative stress level and inflammatory factor expression were measured in gerbils after IS. Western blot and immunofluorescence analyses were conducted to evaluate the expression of related proteins. Metabolomic analyzes IS-related metabolic pathways in urinary metabolites. RA, SA and GA significantly improved the infarct volume and behavioral score of IS gerbils, increased the expression of brain tissue superoxide dismutase (SOD), glutathione (GSH), nitric oxide (NO) and decreased the content of malondialdehyde (MDA), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α). Western blot and immunofluorescence analysis results showed that RA, SA and GA significantly increased the expression of P-Akt, PI3K, HO-1 and KEAP1. Metabolomic studies identified 112 differential metabolites, including L-Proline, Riboflavin, Leukotriene D4, and 7-Methylxanthine, as potential biomarkers of stroke, involving 14 metabolic pathways including riboflavin metabolism, pyrimidine metabolism, and purine metabolism. Our findings indicated that A. coreanum protected against cerebral ischemia injury probably via the PI3K/Akt and KEAP1/NRF2 pathway. A. coreanum before and after processing both had a protective effect against IS brain injury in gerbils. The A. coreanum efficacy was not reduced after processing. Even compared to RA, SA had better efficacy.
Asunto(s)
Aconitum , Gerbillinae , Proteína 1 Asociada A ECH Tipo Kelch , Factor 2 Relacionado con NF-E2 , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Animales , Factor 2 Relacionado con NF-E2/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Masculino , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Accidente Cerebrovascular/metabolismo , Accidente Cerebrovascular/prevención & control , Transducción de Señal/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Accidente Cerebrovascular Isquémico/metabolismo , Accidente Cerebrovascular Isquémico/prevención & controlRESUMEN
Because hydrogen sulfide (H2S) is classified as a gaseous signaling molecule, protein S-sulfhydration is known to be one of the mechanisms by which H2S signals are conducted. PTP1B, a negative regulator in insulin signaling, has been found to be S-sulfhydrated at Cys215-SH to form Cys215-SSH in response to endoplasmic reticulum (ER) stress. Therefore, we aimed to understand the change in PTP1B S-sulfhydration and cellular redox homeostasis in response to insulin stimulation. We demonstrated a feasible PEG-switch method to determine the levels of PTP1B S-sulfhydration. According to the results obtained from HEK293T and MDA-MB-231 cells, insulin induced a change in PTP1B S-sulfhydration that was similar to the change in Insulin receptor substrate 1 (IRS1) phosphorylation in both cell lines. However, insulin-induced PTP1B S-sulfhydration and IRS1 phosphorylation were only significantly affected by metformin in HEK293T cells. Insulin also induced an increase in reactive oxygen species (ROS) in both cell lines. However, the level of H2S, GSH, and GSSG was only significantly affected by insulin and metformin in HEK293T cells. HEK293T cells maintained high levels of H2S and cysteine, but low levels of GSSG and GSH in general compared to MDA-MB-231 cells. From these findings, we suggest that PTP1B activity is modulated by H2S and redox-regulated S-sulfhydration during insulin signaling.
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Sulfuro de Hidrógeno , Insulina , Humanos , Disulfuro de Glutatión/metabolismo , Células HEK293 , Sulfuro de Hidrógeno/farmacología , Sulfuro de Hidrógeno/metabolismo , Insulina/metabolismo , Oxidación-Reducción , Sulfuros/metabolismoRESUMEN
BACKGROUND: Women are vulnerable to depression during postpartum period. While several studies have shown associations between ambient air pollution exposure and depression in general population, there was few studies focused on the effect of various air pollutants on postpartum depression (PPD). OBJECTIVE: This study is designed to explore the association between prenatal exposure to air pollutants and PPD, and to reveal the potential vulnerable exposure time point. METHODS: The study enrolled 10,209 pregnant women who delivered between October 2019 and February 2021 in 5 participating hospitals from 3 cities in China. Edinburgh Postnatal Depression Scale (EPDS) was administered at 6 weeks postpartum to identify PPD symptoms. Associations between PPD symptoms and exposure levels in PM2.5, PM10, SO2, CO, NO2, and O3 averaged over the whole pregnancy and each trimester were estimated using logistic regression models after adjusting for potential confounding factors. Distributed lag models (DLMs) were used to determine the relevant associations in each gestational week. RESULTS: The risk for developing PPD symptoms was significant following a 10 µg/m3 increase in PM10 (aOR = 1.47, 95%CI:1.36-1.59), NO2 (aOR = 1.63, 95%CI:1.44-1.85), and 0.1 mg/m3 increase in CO (aOR = 2.31, 95%CI: 1.99-2.69) during the whole pregnancy. Similar results were also found in exposure during each trimester of pregnancy. Besides, SO2 exposure during the second trimester was a major risk factor for developing PPD symptoms (aOR = 1.10, 95%CI:1.03-1.18). Consistent effects were also observed in DLMs, except for PM2.5 and O3, which showed no significant sensitive windows throughout pregnancy period. CONCLUSION: Exposure to PM10, CO, NO2, and SO2 in pregnancy is associated with increased risks of developing depression at 6 weeks postpartum. Our findings reveal the importance of air pollution control for preventing maternal mental health disorders among the public.
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Contaminantes Atmosféricos , Contaminación del Aire , Contaminantes Ambientales , Efectos Tardíos de la Exposición Prenatal , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , China/epidemiología , Ciudades/epidemiología , Estudios de Cohortes , Depresión , Femenino , Humanos , Material Particulado/análisis , Material Particulado/toxicidad , Periodo Posparto , EmbarazoRESUMEN
BACKGROUND: A fish spike stuck in the throat is a common ear, nose, and throat (ENT) emergency. However, it is very rare for a fish spike to reach the thyroid tissue through the throat, which is very dangerous and can lead to pharyngeal fistula, cervical abscess, mediastinal abscess, and thyroid abscess. Proper and timely management can help reduce complications, especially in elderly patients. CASE SUMMARY: In the case presented here, the causative factor was dentures, but improper management aggravated the condition. In the case presented here, an elderly woman with a history of accidentally swallowing fish bones for 20 d had a sensation of foreign bodies in her throat. Eventually, computed tomography (CT) of the neck showed that the left side of the thyroid gland had a dense shadow in the form of a stripe. CONCLUSION: If a fishbone foreign body is not visible during endoscopic examination but the patient has significant symptoms, the surgeon should be aware that the fishbone may be lodged in the thyroid. To avoid a misdiagnosis, ultrasound, CT, and other tests can be used to clarify the diagnosis. T The first step in treating a fish bone in the thyroid gland is to determine the position of the foreign body and the extent of the infection, and to develop a personalized surgical plan for its removal. At the same time, scientific information should be made available to the general public so that people know that if a fish bone is accidentally lodged, they should not force it to be swallowed or be spit out by inducing vomiting, which are incorrect methods and may aggravate the condition or even cause it to migrate outside the cavity, leading to serious complications, as in this reported case.
RESUMEN
BACKGROUND: Antenatal depression might cause adverse pregnancy outcomes. However, previous study results were inconsistent, especially in the low- and middle- income countries. We aimed to study the association between antenatal depression and adverse perinatal outcomes in a Chinese population. METHODS: We performed a prospective cohort study and enrolled pregnant women from January 2020 to January 2021. Antenatal depressive symptoms in the third trimester of pregnancy were evaluated by the Edinburgh Postpartum Depression Scale (EPDS). Baseline characteristics and pregnancy outcomes were recorded. After adjusting for confounding factors (age, occupation, education level, and annual income), multivariate logistic regression analysis was applied to evaluate the associations between antenatal depression and pregnancy outcomes. RESULTS: Among the 5209 participants, 1448 (27.7 %) pregnant women were positive for depression. After adjusting for potential confounders, women with antenatal depressive symptoms were significantly more likely to deliver prematurely [Odds ratio (OR) = 1.404, 95 % confidence interval (CI) = 1.020-1.933, P = 0.037] and receive cesarean section (OR = 1.154, 95 % CI = 1.002-1.331, P = 0.048). LIMITATIONS: EPDS, not a structured diagnostic interview, was used for psychological assessment. In addition, we only screened the women in their third trimester in a single research center. The association between the duration of antenatal depression and perinatal outcomes was not evaluated. CONCLUSIONS: Depressive symptoms were common among Chinese women in their third trimester of pregnancy. Women with antenatal depressive symptoms had increased cesarean section and preterm delivery risks. Screening and treatment for antenatal depression are needed during the prenatal care.
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Depresión Posparto , Complicaciones del Embarazo , Recién Nacido , Embarazo , Femenino , Humanos , Depresión/epidemiología , Depresión/diagnóstico , Depresión Posparto/diagnóstico , Depresión Posparto/epidemiología , Depresión Posparto/psicología , Estudios Prospectivos , Cesárea , Complicaciones del Embarazo/psicología , PartoRESUMEN
BACKGROUND: Depression and anxiety are common among pregnant women. Internet-delivered psychological therapies such as cognitive behavioral therapy (iCBT) have been developed to increase accessibility and address common help-seeking barriers, especially during pandemic period. The objective of this trial is to evaluate the short-term and long-term effects of iCBT on reducing depressive symptoms among pregnant women during the COVID-19 pandemic with the overall goal of preventing depression recurrence in the first 12 months postpartum. METHODS: A multi-site randomized controlled trial will be conducted where 300 pregnant women early in their third trimester will be screened for depression symptoms using the Edinburgh Postnatal Depression Scale (EPDS) during a routine obstetrical visit. Eligible and consenting women with a score greater than 9 will be randomly allocated (1:1) to either intervention group or control group. ICBT involving the completion of 7 weekly online modules will be delivered via a well-designed perinatal mental healthcare app. The primary objective is to evaluate the effect of iCBT on reducing depression symptoms among pregnant Chinese women starting from their third trimester. The secondary objectives are to examine the effect of iCBT on anxiety, sleep quality, social support, parenting stress, co-parenting relationship, and infant development. DISCUSSION: This multi-center randomized controlled trial has been planned in accordance with best practices in behavioral trial design. The internet-based intervention addressed the needs of pregnant women during a major pandemic where face-to-face therapy is not preferable. The trial has a relatively large sample size with sufficient power to evaluate the efficacy of iCBT intervention for the primary and secondary outcomes. One year follow-up evaluation in the study is designed to determine the longer-term effect of the intervention on both maternal and infant outcomes. Although a limitation is the assessment of depression and anxiety using self-report measures, these easily incorporated and maternal-preferred assessments allow for real-life scalability if the intervention is proven to be effective. ETHICS AND DISSEMINATION: Ethics was approved by the institutional review board of International Peace Maternity and Child Health Hospital (GKLW2020-25). Dissemination of results will be published in peer-reviewed academic journals and presented at scientific conferences. TRIAL STATUS: The first patient was enrolled on 19 August 2020. To date, 203 participants have met eligibility requirements and been randomized to either the intervention group or control group. Data collection aims to be complete in September 2022. Date and version identifier: 2020715-version1.0. TRIAL REGISTRATION: ChiCTR2000033433. Registered 31 May 2020, http://www.chictr.org.cn/showproj.aspx?proj=54482 .
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COVID-19 , Terapia Cognitivo-Conductual , Niño , Terapia Cognitivo-Conductual/métodos , Depresión/diagnóstico , Depresión/terapia , Femenino , Humanos , Internet , Estudios Multicéntricos como Asunto , Pandemias , Embarazo , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
Osteoarthritis (OA) is the most common inflammatory joint disease that is mainly characterized by articular cartilage destruction. Forkhead box M1 (FOXM1) is a transcription factor that acts as a critical mediator of inflammatory response. However, the role of FOXM1 in OA has not been investigated. Interleukin (IL)-1ß is a major proinflammatory cytokine, which is associated with cartilage destruction in the pathophysiology of OA. In the present study, we used IL-1ß to stimulate chondrocytes for the establishment of OA in vitro model. We found that FOXM1 was up-regulated in IL-1ß-induced chondrocytes. Knockdown of FOXM1 attenuated IL-1ß-caused decrease in cell viability. Knockdown of FOXM1 suppressed the IL-1ß-induced production of inflammatory cytokines including tumor necrosis factor (TNF)-α, and IL-6. Besides, several inflammatory mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthases (iNOS), and cyclooxygenase-2 (COX-2) were also repressed by knockdown of FOXM1. FOXM1 silencing also inhibited the production of matrix metalloproteinases (MMPs) including MMP-3 and MMP-13. Furthermore, we found that knockdown of FOXM1 blocked the IL-1ß-induced NF-κB activation in chondrocytes. These findings indicated that FOXM1 might play an important role in the pathogenesis of OA, suggesting that FOXM1 might be a potential therapeutic target for the treatment of OA.
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Condrocitos/inmunología , Citocinas/inmunología , Proteína Forkhead Box M1/inmunología , Osteoartritis/inmunología , Células Cultivadas , Proteína Forkhead Box M1/genética , Silenciador del Gen , Humanos , FN-kappa B/inmunología , ARN Interferente Pequeño/genéticaRESUMEN
A quantitative relationship between power densities of blood pressure (PBP) and sympathetic nerve activity (PSNA) in a low-frequency range (LF, 0.016-0.85 Hz), expressed as PSNA=PBPxax10bx(frequency) was proposed in pentobarbital-anesthetized rats. For evaluating the general applicability of this equation, the quantitative relationship of power density ratio Hf=PBP/PSNA across frequency was tested in a conscious state. Wistar rats were chronically instrumented with a femoral artery catheter and recording electrode around the renal sympathetic nerve. The blood pressure and renal sympathetic nerve activity were monitored both under pentobarbital anesthesia and in a conscious state. Linear regression analysis of the relationship between the frequency and logarithmic magnitude of the power density ratio in the LF range revealed excellent fit in both conditions (r=-0.96+/-0.01 and -0.93+/-0.01 for anesthetized and conscious rats, respectively). Comparing the regression lines, rats under pentobarbital anesthesia had significantly larger values for the y-intercept and slope compared to rats in a conscious state (y-intercepts: 0.80+/-0.09>0.53+/-0.08; slopes: -2.86+/-0.26>-1.62+/-0.21). Our results demonstrate that it is also feasible to use the weighted PBP in LF as a quantitative index of sympathetic variability in conscious rats, but the evaluation of possible complications controlling the regression parameters is called for.
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Arterias/fisiología , Presión Sanguínea/efectos de los fármacos , Presión Sanguínea/fisiología , Pentobarbital/farmacología , Fibras Simpáticas Posganglionares/efectos de los fármacos , Fibras Simpáticas Posganglionares/fisiología , Potenciales de Acción/efectos de los fármacos , Potenciales de Acción/fisiología , Adyuvantes Anestésicos/farmacología , Animales , Arterias/inervación , Estado de Conciencia/fisiología , Análisis de Fourier , Masculino , Músculo Liso Vascular/inervación , Músculo Liso Vascular/fisiología , Ratas , Ratas Wistar , Análisis de Regresión , Arteria Renal/inervación , Arteria Renal/fisiología , Estadística como Asunto/métodos , Vasoconstricción/efectos de los fármacos , Vasoconstricción/fisiologíaRESUMEN
This paper presents a method that allows two wheeled, mobile robots to navigate unknown environments while cooperatively carrying an object. In the navigation method, a leader robot and a follower robot cooperatively perform either obstacle boundary following (OBF) or target seeking (TS) to reach a destination. The two robots are controlled by fuzzy controllers (FC) whose rules are learned through an adaptive fusion of continuous ant colony optimization and particle swarm optimization (AF-CACPSO), which avoids the time-consuming task of manually designing the controllers. The AF-CACPSO-based evolutionary fuzzy control approach is first applied to the control of a single robot to perform OBF. The learning approach is then applied to achieve cooperative OBF with two robots, where an auxiliary FC designed with the AF-CACPSO is used to control the follower robot. For cooperative TS, a rule for coordination of the two robots is developed. To navigate cooperatively, a cooperative behavior supervisor is introduced to select between cooperative OBF and cooperative TS. The performance of the AF-CACPSO is verified through comparisons with various population-based optimization algorithms for the OBF learning problem. Simulations and experiments verify the effectiveness of the approach for cooperative navigation of two robots.