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Autosomal dominant polycystic kidney disease is caused by mutations in the membrane receptor PKD1 or the cation channel PKD2. TACAN (also termed TMEM120A), recently reported as an ion channel in neurons for mechanosensing and pain sensing, is also distributed in diverse non-neuronal tissues, such as kidney, heart and intestine, suggesting its involvement in other functions. In this study, we found that TACAN is in a complex with PKD2 in native renal cell lines. Using the two-electrode voltage clamp in Xenopus oocytes, we found that TACAN inhibits the channel activity of PKD2 gain-of-function mutant F604P. TACAN fragments containing the first and last transmembrane domains interacted with the PKD2 C- and N-terminal fragments, respectively. The TACAN N-terminus acted as a blocking peptide, and TACAN inhibited the function of PKD2 by the binding of PKD2 with TACAN. By patch clamping in mammalian cells, we found that TACAN inhibits both the single-channel conductance and the open probability of PKD2 and mutant F604P. PKD2 co-expressed with TACAN, but not PKD2 alone, exhibited pressure sensitivity. Furthermore, we found that TACAN aggravates PKD2-dependent tail curvature and pronephric cysts in larval zebrafish. In summary, this study revealed that TACAN acts as a PKD2 inhibitor and mediates mechanosensitivity of the PKD2-TACAN channel complex. KEY POINTS: TACAN inhibits the function of PKD2 in vitro and in vivo. TACAN N-terminal S1-containing fragment T160X interacts with the PKD2 C-terminal fragment N580-L700, and its C-terminal S6-containing fragment L296-D343 interacts with the PKD2 N-terminal A594X. TACAN inhibits the function of the PKD2 channel by physical interaction. The complex of PKD2 with TACAN, but not PKD2 alone, confers mechanosensitivity.
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Rim Policístico Autossômico Dominante , Peixe-Zebra , Animais , Canais de Cátion TRPP/genética , Canais de Cátion TRPP/metabolismo , Canais Iônicos/genética , Rim Policístico Autossômico Dominante/genética , Rim Policístico Autossômico Dominante/metabolismo , Rim/metabolismo , Mamíferos/metabolismoRESUMO
BACKGROUND: Water shortage caused by global warming seriously affects the yield and quality of vegetable crops. ß-carotene, the lipid-soluble natural product with important pharmacological value, is abundant in celery. Transcription factor MYB family extensively disperses in plants and plays regulatory roles in carotenoid metabolism and water scarcity response. RESULTS: Here, the AgMYB5 gene encoding 196 amino acids was amplified from celery cv. 'Jinnanshiqin'. In celery, the expression of AgMYB5 exhibited transactivation activity, tissue specificity, and drought-condition responsiveness. Further analysis proved that ectopic expression of AgMYB5 increased ß-carotene content and promoted drought tolerance in transgenic Arabidopsis thaliana. Moreover, AgMYB5 expression promoted ß-carotene biosynthesis by triggering the expression of AtCRTISO and AtLCYB, which in turn increased antioxidant enzyme activities, and led to the decreased contents of H2O2 and MDA, and the inhibition of O2- generation. Meanwhile, ß-carotene accumulation promoted endogenous ABA biosynthesis of transgenic Arabidopsis, which resulted in ABA-induced stomatal closing and delayed water loss. In addition, ectopic expression of AgMYB5 increased expression levels of AtERD1, AtP5CS1, AtRD22, and AtRD29. CONCLUSIONS: The findings indicated that AgMYB5 up-regulated ß-carotene biosynthesis and drought tolerance of Arabidopsis.
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Apium , Arabidopsis , Arabidopsis/metabolismo , beta Caroteno , Apium/genética , Apium/metabolismo , Resistência à Seca , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Verduras/genética , Verduras/metabolismo , Peróxido de Hidrogênio/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Plantas Geneticamente Modificadas/metabolismo , Estresse Fisiológico/genética , Antioxidantes/metabolismo , Secas , Água/metabolismo , Regulação da Expressão Gênica de Plantas , Ácido Abscísico/metabolismoRESUMO
Climate Change related concerns affect multiple international and national policy forefronts. Globally, conflicts over renewables industry between the developed and emerging economies have affected the provision of green goods-thus slowing the overall welfare of global environmental governance. This article argues that the above phenomenon is a new form of green dilemma which arises from the long-lasting issue of balancing environmental protection and economic gains. It further tracks the historical evolutionary change of green dilemma, from version 1.0 to 2.0 to the current avatar of Green Dilemma 3.0. By developing the Green Dilemma Framework, the article aims to uncover the logic underlying the industrial policies and trade conflicts between the developed and emerging economies in their energy transitions. Utilizing the US vs China and US vs India conflicts in the solar PV industries as the two group of cases, the key feature of Green Dilemma 3.0 is illustrated as the conflict over status and control of the global division of labor in the new energy industry. This article offers a novel perspective on global inequality by deconstructing the unequal global production system that can act to restrict the optimization of energy use and production in tackling climate change and thus successively hindering global environmental governance in its realization of optimal results. Underneath global climate change governance, there is an unequal global production network and political system, and both these follow a core, semi-periphery, and periphery distribution of power structure. We argue that the inequality of global production system suppresses the effects of subsidy competition and erodes the economic foundation of global climate governance.
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Conservação dos Recursos Naturais , Política Ambiental , China , Índia , Energia Renovável , Fatores SocioeconômicosRESUMO
Aim: The objective of this study was to assess whether an elderly patient's frailty was associated with acute kidney injury (AKI) and to examine whether severe frailty group had an increased risk of AKI than mild-moderate group.Methods: We searched The Cochrane Library, PubMed, and EMBASE for relevant studies without language limitations before 1 March 2019 with a priori defined inclusion and exclusion criteria. Five population-based cohort studies were included for systematic review and meta-analysis.Results: Compared with the control group, the frailty group is significantly associated AKI (Odds Ratio = 2.05; 95% CI: 1.23-3.43). The moderate-severe frailty group has an increased risk of AKI than mild frailty group (Hazard Ratio = 2.87; 95% CI: 1.60-5.17.Conclusion: In conclusion, the available best evidence support an association between frailty and AKI among elder patients, thus relevant interventions should be taken among elderly under potential risk of AKI.
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Injúria Renal Aguda , Idoso Fragilizado , Idoso , Humanos , Medição de RiscoRESUMO
PURPOSE: To investigate the changes of cerebral hemodynamics pre- and post-ventricular drainage in patients with posttraumatic acute diffuse brain swelling. METHODS: Twenty-four cases of traumatic diffuse brain swelling were analyzed retrospectively. Patients in nonsurgical group were treated by medicine therapy. Patients in surgical group were treated by external ventricular drainage plus medicine therapy. The first CT perfusion scan was completed within 4-5 h after trauma and scanned again after 7 days. The changes of perfusion parameters in area-of-interest in two groups were analyzed and compared before and after treatment. RESULTS: Compared with the nonsurgical group, the value of cerebral blood volume, cerebral blood flow and mean transit time in bilateral frontal temporoparietal grey matter, basal ganglia, cerebellum, and brain stem at pre- and post-therapy were increased significantly (p < 0.05) in surgical group, and consequently the prognosis of patients undergoing surgery was also better than that of nonsurgical group. CONCLUSION: External ventricular drainage can improve cerebral perfusion and increase survival quality for the patients with posttraumatic acute diffuse brain swelling.
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Edema Encefálico/fisiopatologia , Lesões Encefálicas/complicações , Encéfalo/fisiopatologia , Drenagem , Hemodinâmica , Adulto , Idoso , Edema Encefálico/terapia , Circulação Cerebrovascular , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Transient receptor potential (TRP) polycystin-3 (TRPP3) is a non-selective cation channel activated by Ca2+ and protons and is involved in regulating ciliary Ca2+ concentration, hedgehog signaling and sour tasting. The TRPP3 channel function and regulation are still not well understood. Here we investigated regulation of TRPP3 by calmodulin (CaM) by means of electrophysiology and Xenopus oocytes as an expression model. We found that TRPP3 channel function is enhanced by calmidazolium, a CaM antagonist, and inhibited by CaM through binding of the CaM N-lobe to a TRPP3 C-terminal domain not overlapped with the EF-hand. We further revealed that the TRPP3/CaM interaction promotes phosphorylation of TRPP3 at threonine 591 by Ca2+/CaM-dependent protein kinase II, which mediates the inhibition of TRPP3 by CaM.
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METHODS: The databases Pubmed, and the National Library of Medicine were searched for literature. All papers on celebral stroke and transient receptor potential ion channels were considered. RESULTS: Stroke is the second leading cause of death and disability, with an increasing incidence in developing countries. About 75 per cent of strokes are caused by occlusion of cerebral arteries, and substantial advances have been made in elucidating mechanisms how stroke affects the brain. Transient receptor potential (TRP) ion channels are calcium-permeable channels highly expressed in brain that drives Ca2+ entry into multiple cellular compartments. TRPC1/3/4/6, TRPV1/2/4, and TRPM2/4/7 channels have been implicated in stroke pathophysiology. CONCLUSIONS: Although the precise mechanism of transient receptor potential ion channels in cerebral stroke is still unclear, it has the potential to be a therapeutic target for patients with stroke if developed appropriately. Hence, more research is needed to prove its efficacy in this context.
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Acidente Vascular Cerebral , Canais de Cátion TRPM , Canais de Potencial de Receptor Transitório , Humanos , Encéfalo/metabolismo , Cálcio/metabolismo , Canais de Cátion TRPM/metabolismoRESUMO
PURPOSE: Stroke is an acute cerebrovascular disease. Astragaloside IV (AS-IV) is an active ingredient extracted from Astragalus membranaceus with an established therapeutic effect on central nervous system diseases. This study examined the neuroprotective properties and possible mechanisms of AS-IV in stroke-triggered early brain injury (EBI) in a rat transient middle cerebral artery occlusion (MCAO) model. METHODS: The neurological scores and brain water content were analyzed. 2,3,5-triphenyl tetrazolium chloride (TTC) staining was utilized to determine the infarct volume, neuroinflammatory cytokine levels, and ferroptosis-related genes and proteins, and neuronal damage and molecular mechanisms were evaluated by terminal deoxynucleotidyl transferase dutp nick-end labeling (TUNEL) staining, western blotting, and real-time polymerase chain reaction. RESULTS: AS-IV administration decreased the infarct volume, brain edema, neurological deficits, and inflammatory cytokines TNF-α, interleukin-1ß (IL-1ß), IL-6, and NF-κB, increased the levels of SLC7A11 and glutathione peroxidase 4 (GPX4), decreased lipid reactive oxygen species (ROS) levels, and prevented neuronal ferroptosis. Meanwhile, AS-IV triggered the Nrf2/HO-1 signaling pathway and alleviated ferroptosis due to the induction of stroke. CONCLUSIONS: Hence, the findings of this research illustrate that AS-IV administration can improve delayed ischemic neurological deficits and decrease neuronal death by modulating nuroinflammation and ferroptosis via the Nrf2/HO-1 signaling pathway.
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Lesões Encefálicas , Ferroptose , Acidente Vascular Cerebral , Ratos , Animais , Fator 2 Relacionado a NF-E2/metabolismo , Doenças Neuroinflamatórias , Ratos Sprague-Dawley , Acidente Vascular Cerebral/tratamento farmacológico , Transdução de Sinais , Citocinas/metabolismo , InfartoRESUMO
Introduction: Spontaneous subarachnoid hemorrhage (SAH), is a disorder that may be fatal and is primarily caused by a ruptured brain aneurysm. Despite significant leaps forward in the methods to produce aneurysms, the long-term outcomes did not much improve. Pioglitazone is a medication that has been authorized by the FDA as an agonist for the peroxisome proliferator-activated receptor-gamma (PPARγ). Pioglitazone or PPARγ has neuroprotective benefits in animal experiments both during and after traumatic brain injury (TBI) and SAH. Nevertheless, the treatment impact of Pioglitazone on humans is still unknown at this time. As a result, we will conduct a randomized, double-blind, placebo-controlled trial to explore the impact of pioglitazone on SAH. Methods/Design: This trial will recruit 400 patients with SAH from four Chinese hospitals. These patients will be equally and randomly assigned to Pioglitazone and placebo control groups for up to 30 days. Scores on the modified Rankin scale (mRS) are the primary outcomes. The secondary outcomes are a 30-day all-cause mortality rate, 6 months of Montreal cognitive assessment (Mo-CA), delayed cerebral ischemia, the requirement for intensive care, the incidence of sepsis, etc. All serious adverse events (SAEs) were recorded during the hospital. Every primary and safety analysis was conducted based on the intention-to-treat technique. The participants were given either a matching placebo or 15 mg of pioglitazone, with dose titrated to a target of 45 mg daily. Data on the therapeutic use of pioglitazone after SAH will be provided as a consequence of the findings of this experiment. In addition, this pilot trial is the first to prospectively investigate the effectiveness and safety of pioglitazone in patients with SAH. Ethics and dissemination: Ethics approval was obtained from the Medical Ethics Committee of 904th Hospital of Joint Logistic Support Force of PLA (Wuxi Taihu Hospital, approval No. 20220701). The findings of the trial will be presented at conferences, discussed in relevant patient groups, and published in peer-reviewed journals. Clinical Trial Registration: clinicaltrials.gov, identifier ChiCTR2200062954.
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OBJECTIVE: To investigate the clinical features and treatment strategy of dissymmetric bilateral frontal contusion, and to summarize our experience in treating these patients by minimally invasive surgery. METHODS: Over the past 3 years, we have treated a total of 31 patients with dissymmetric bilateral frontal contusion using endoscopy-assisted unilateral cerebral falx incision. Other 30 patients treated by routine bilateral approaches within the same period were taken as control. RESULTS: Seventeen cases (54.8%) in the unilateral operation group survived and were in good condition, 8 (25.8%) had moderate disability, 4 (12.9%) had severe disability, 1 (3.2%) was in vegetative state, and 1 (3.2%) died. Compared with the control group, the Glasgow Outcome Scale score was not significantly different in the unilateral operation group, but the operation time, blood transfusion volume, the length of hospital stay, the incidences of mental disorder and olfactory nerve injury were greatly reduced in the unilateral operation group. CONCLUSIONS: Endoscopy-assisted unilateral cerebral falx incision can shorten the operation time, reduce surgical trauma and complications in treatment of patients with dissymmetric bilateral frontal contusion. It can obviously diminish the chance of delayed intracerebral hematoma and subsequently minimize the incidences of subfalcial and centrencephalic herniation.
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Contusões , Endoscopia , Lesões Encefálicas , Dura-Máter , Humanos , Resultado do TratamentoRESUMO
Recently, the robotic arm control system based on a brain-computer interface (BCI) has been employed to help the disabilities to improve their interaction abilities without body movement. However, it's the main challenge to implement the desired task by a robotic arm in a three-dimensional (3D) space because of the instability of electroencephalogram (EEG) signals and the interference by the spontaneous EEG activities. Moreover, the free motion control of a manipulator in 3D space is a complicated operation that requires more output commands and higher accuracy for brain activity recognition. Based on the above, a steady-state visual evoked potential (SSVEP)-based synchronous BCI system with six stimulus targets was designed to realize the motion control function of the seven degrees of freedom (7-DOF) robotic arm. Meanwhile, a novel template-based method, which builds the optimized common templates (OCTs) from various subjects and learns spatial filters from the common templates and the multichannel EEG signal, was applied to enhance the SSVEP recognition accuracy, called OCT-based canonical correlation analysis (OCT-CCA). The comparison results of offline experimental based on a public benchmark dataset indicated that the proposed OCT-CCA method achieved significant improvement of detection accuracy in contrast to CCA and individual template-based CCA (IT-CCA), especially using a short data length. In the end, online experiments with five healthy subjects were implemented for achieving the manipulator real-time control system. The results showed that all five subjects can accomplish the tasks of controlling the manipulator to reach the designated position in the 3D space independently.
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OBJECTIVE: As the reproduction season's effect on the mental health status is unknown, this study aims to explore the association between seasons and postpartum depression. METHODS: A comprehensive search in databases, including PubMed, Cochrane Library, and EMBASE, was performed to identify studies reporting the relationship between reproduction season and postpartum depression. The latter was assessed using certain methods. Moreover, the study design and duration, sample size, the definition of four seasons, outcome assessment, method, and conclusion were extracted. Two independent authors screened the studies independently, and PRISMA 2020 was used as the reporting standard (PRISMA registration ID is 284524). RESULTS: A total of five studies including 103,986 participants met our criteria. In the sensitivity analysis, the result of the meta-analysis shows that women who gave birth in spring, summer, or autumn had a lower risk of postpartum depression compared to those who gave birth in winter (RR: 0.83; 95% confidence interval [CI]: 0.78-0.88). CONCLUSION: Women who gave birth in the other seasons were less likely to have postpartum depression compared to those who gave birth in winter. This result could help couples make overall decisions and help the puerpera take preventive measures against postpartum depression.
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Depressão Pós-Parto , Estudos de Coortes , Depressão Pós-Parto/epidemiologia , Feminino , Humanos , Parto , Gravidez , Estações do AnoRESUMO
In plants, NO has been proved the function of improving abiotic stress resistance. However, the role of NO in the lignin metabolism of okra under cold stress has not been clarified. Here, histochemical staining and lignin content analysis showed that cold stress promoted the lignin accumulation of cold stored okra pods, and NO inhibited the lignin accumulation and delayed lignification process. To better understand the roles of NO in okra cold stress resistance mechanism, the full-length transcriptome data of 'Hokkaido' was analyzed. The SNP-treated okra transcriptome and cPTIO-treated okra transcriptome were obtained. A total of 41957 unigenes were screened out from three groups at 10 d, among which, 33, 78 and 18 DEGs were found in ddH2O-treat, SNP-treat and cPTIO-treat group, respectively. Transcriptomic data suggested that the genes involved in lignin biosynthesis showed downregulation under SNP treatment. Transcriptomic data and enzyme activity showed that exogenous NO significantly promoted the biosynthesis of endogenous NO by enhancing NOS activity. Transcriptomic data and plant hormone data showed that NO played an important role in the process of inhibiting the ethylene and ABA synthesis mechanism of okra and thereby reducing the endogenous ethylene and ABA content under chilling stress. Relevant physiological data showed that NO helped to the protection of ROS scavenging system and removed the MDA and H2O2 induced by cold stress. These results provided a reference for studying the molecular mechanism of nitric oxide delaying the lignification of okra, and also provided a theoretical basis for postharvest storage of vegetables.
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Abelmoschus , Perfilação da Expressão Gênica , Peróxido de Hidrogênio , Lignina , Óxido Nítrico , TranscriptomaRESUMO
P-glycoprotein (P-gp) acts as a pump to transport cytotoxic drugs out of cells and is upregulated in cancer cells. Suppressing the expression of P-gp is an effective strategy to overcome multidrug resistance in cancer chemotherapy. Temozolomide (TMZ) is the recommended drug for the standard treatment of patients with glioblastoma, but its clinical application is restricted due to drug resistance. Transient receptor potential channel-5 (TRPC5), a Ca2+-permeable channel, has been attributed to a different drug resistance mechanism except DNA repair system; therefore, we aimed to elucidate the mechanism regarding the role of TRPC5 in TMZ resistance. TRPC5 and P-glycoprotein (P-gp) are upregulated in TMZ-resistant glioblastoma cell lines. The downregulation of TRPC5 inhibited P-gp expression and led to a significant reversal of TMZ resistance in TMZ-resistant cell lines. TRPC5-siRNA restricted the growth of tumour xenografts in an athymic nude mouse model of TMZ-resistant cells. In specimens from patients with recurrent glioblastoma, TRPC5 was found to be highly expressed, accompanied by the upregulation of P-gp expression. The nuclear factor of activated T cell isoform c3 (NFATc3), which acts as a transcriptional factor, bridges TRPC5 activity to P-gp induction. In conclusion, these results demonstrate the functional role of the TRPC5-NFATc3-P-gp signalling pathway in TMZ resistance in glioblastoma cells.
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OBJECTIVE: To study the effect and indications of intracranial pressure (ICP) monitoring for frontal lobe contusion patients. METHODS: During January 2005-December 2008, 34 cases of frontal lobe contusion received ICP monitoring in our department (monitoring group). Different treatment protocols were adopted according to the results of ICP. Meanwhile 46 cases of same type of head-injured patients who did not undergo ICP monitoring served as control group. RESULTS: We found that ICP elevated dramatically within 24 hours after head injury if the contusions were located in frontal longitudinal dehiscence, bilateral undersurface of frontal lobe or dispersed in bilateral lobe. After half a year follow-up and on the basis of Glasgow Coma Scale assessment, the monitoring group showed better outcome than the control group with good recovery in 24 cases (70.6%) , moderate disability in 7 cases (20.6%), severe disability in 2 (5.88%) and death in 1 (2.94%). The outcome of control group displayed good condition in 25 cases (54.3%), moderate disabilities in 8 (17.4%), severe disability in 7 (15.2%), and death in 6 (13.0%). CONCLUSIONS: Frontal lobe contusions are vulnerable and complex head injuries, especially when the contusions are located in frontal longitudinal dehiscence, bilateral undersurface of frontal lobe or diffused in bilateral lobes. These patients should undergo ICP monitoring regardless of their consciousness status. If ICP elevates over 25 mm Hg, the craniotomy is mandatory and will markedly reduce the mortality and disability of these patients.
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Contusões/fisiopatologia , Traumatismos Craniocerebrais/fisiopatologia , Lobo Frontal/lesões , Pressão Intracraniana , Adolescente , Adulto , Idoso , Feminino , Escala de Coma de Glasgow , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND Traumatic torcular herophili epidural hematoma is a rare and specific type of traumatic brain injury that is technically difficult to treat and, more critically, can lead to malignant encephalocele during the operation. CASE REPORT A 40-year-old man presented to our hospital 2 h after a motor vehicle crash. Emergency cranial CT showed a frontotemporal subdural hematoma; 3 h after the patient was admitted, the GCS score decreased to 8 and cranial CT re-examination showed that the frontotemporal subdural hematoma was significantly larger than before. We surgically evacuated the hematoma and the patient experienced acute encephalocele 1 h later. An intra-operative cranial CT re-examination showed a large epidural torcular herophili hematoma. Then, via a posterior fossa craniotomy at the torcular herophili, the source of the hemorrhage was identified as the torcular herophili and diploic veins. We used Gelfoam for compression to establish hemostasis and the occipital fascia to repair the broken dura of the torcular herophili and maintain appropriate tension. One month after the injury, CT scans showed absorption of the brain contusion and intracerebral hematoma and reduced cerebral edema, and the patient showed complete resolution of the injury, without neurological dysfunction. CONCLUSIONS If the first CT scan shows no hematoma in the brain, it can be easy to ignore this complication during the operation. Attention should be paid to confirming a diagnosis as quickly as possible to improve the prognosis of patients with traumatic brain injuries.
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Encefalocele/diagnóstico por imagem , Hematoma Epidural Craniano/diagnóstico por imagem , Hematoma Subdural/diagnóstico por imagem , Adulto , Lesões Encefálicas Traumáticas/complicações , Encefalocele/etiologia , Hematoma Epidural Craniano/complicações , Hematoma Subdural/etiologia , Humanos , Masculino , Tomografia Computadorizada por Raios XRESUMO
Purpose: Stroke is an acute cerebrovascular disease. Astragaloside IV (AS-IV) is an active ingredient extracted from Astragalus membranaceus with an established therapeutic effect on central nervous system diseases. This study examined the neuroprotective properties and possible mechanisms of AS-IV in stroke-triggered early brain injury (EBI) in a rat transient middle cerebral artery occlusion (MCAO) model. Methods: The neurological scores and brain water content were analyzed. 2,3,5-triphenyl tetrazolium chloride (TTC) staining was utilized to determine the infarct volume, neuroinflammatory cytokine levels, and ferroptosis-related genes and proteins, and neuronal damage and molecular mechanisms were evaluated by terminal deoxynucleotidyl transferase dutp nickend labeling (TUNEL) staining, western blotting, and real-time polymerase chain reaction. Results: AS-IV administration decreased the infarct volume, brain edema, neurological deficits, and inflammatory cytokines TNF-α, interleukin-1ß (IL-1ß), IL-6, and NF-κB, increased the levels of SLC7A11 and glutathione peroxidase 4 (GPX4), decreased lipid reactive oxygen species (ROS) levels, and prevented neuronal ferroptosis. Meanwhile, AS-IV triggered the Nrf2/HO-1 signaling pathway and alleviated ferroptosis due to the induction of stroke. Conclusion: Hence, the findings of this research illustrate that AS-IV administration can improve delayed ischemic neurological deficits and decrease neuronal death by modulating nuroinflammation and ferroptosis via the Nrf2/HO-1 signaling pathway.
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Animais , Ratos , Saponinas , Lesões Encefálicas/terapia , Extratos Vegetais/administração & dosagem , Astrágalo/química , Fator 2 Relacionado a NF-E2/análise , Neuroimunomodulação , Acidente Vascular Cerebral/complicações , FerroptoseRESUMO
Bile acid metabolism was reported to be involved in glucose metabolism homeostasis. However, the exact relationship between bile acid and glucose metabolism as well as insulin sensitivity is not clarified. Therefore, we sought to investigate the association between insulin sensitivity and hyperbileacidemia in type 2 diabetic and nondiabetic population.This community-based cross-sectional study included 9603 residents from Jiading, Shanghai, China, who were 40 years and older. Standardized questionnaire, anthropometric measurements and laboratory tests were conducted. Homeostasis model assessment of insulin resistance (HOMA-IR) ≥ 2.7 was defined as insulin resistance and fasting TBA ≥ 10 mmol/L was defined as hyperbileacidemia.Multivariate stepwise regression analysis revealed that HOMA-IR, age, and male sex were positively associated with hyperbileacidemia in both nondiabetic and diabetic participants. In multivariate logistic models, participants with insulin resistance had significantly higher risk of hyperbileacidemia compared to those who have no insulin resistance, in both nondiabetic and diabetic population (nondiabetic: ORâ=â1.76; 95% CI 1.42-2.19; Pâ<â0.001; diabetic: ORâ=â1.56; 95% CI 1.06 - 2.31; Pâ=â0.025, respectively). Further adjustment for the HbA1c level in diabetic population did not change the significant association (ORâ=â1.59; 95% CI 1.06 - 2.40; Pâ=â0.024). In nondiabetic participants, each 1-unit increment of HOMA-IR conferred an 18% higher risk of hyperbileacidemia (95% CI 1.04-1.35; Pâ=â0.013), whereas in diabetic participants, this association was similar but not significant (95% CI 0.95-1.59; Pâ=â0.117).Insulin resistance was positively associated with hyperbileacidemia in both nondiabetic and diabetic population. The increase in the bile acid level in insulin-resistant population regardless of status of diabetes and glucose level indicated the important role of insulin resistance in the regulation of bile acid metabolism in human.
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Ácidos e Sais Biliares/sangue , Glicemia , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Adulto , Fatores Etários , Glicemia/análise , Glicemia/metabolismo , China/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Distribuição Aleatória , Fatores Sexuais , Estatística como AssuntoRESUMO
Studying publication volumes at the country level is key to understanding and improving a country's research system. PubMed is a public search engine of publications in all life sciences areas. Here, we show how this search engine can be used to assess the outputs of life science-related research by country. We have measured the numbers of publications during different time periods based on the country of affiliation of the first authors. Moreover, we have designed scores, which we have named Attraction Scores, to appraise the relative focus either toward particular types of studies, such as clinical trials or reviews, or toward specific research areas, such as public health and pharmacogenomics, or toward specific topics, for instance embryonic stem cells; we have also investigated a possible use of these Attraction Scores in connection with regulatory policies. We have weighed the statistics against general indicators such as country populations and gross domestic products (GDP). During the 5-year period 2008-2012, the United States was the country with the highest number of publications and Denmark the one with the highest number of publications per capita. Among the 40 countries with the highest GDPs, Israel had the highest publications-to-GDP ratio. Among the 20 countries with the most publications, Japan had the highest Attraction Score for induced pluripotent stem (iPS) cells and Italy the highest proportion of review publications. More than 50% of publications in English were from countries in which English is not the primary language. We show an assorted and extensive collection of rankings and charts that will inform scholars and policymakers in studying and improving the research systems both at the national and international level.