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Safranal, a main component of Crocus sativus, is suggested to have neuroprotective effects. The aim of this study was to investigate the effect of safranal and nanostructured lipid vehicle (NLV) carried safranal in acute and chronic experimental mice models of epilepsy. In PILO acute seizure model, safranal dose-dependently extended latency to generalized seizure, decreased the highest seizure stages and the number of generalized seizures. Moreover, NLV carried safranal further enhanced the anti-seizure effect, which is comparable to the action of sodium valproate. Meanwhile, NLV carried safranal reduced and delayed the electroencephalogram spectra power after pilocarpine injection. In histological aspect, safranal dose-dependently reduced the loss of neurons induced by seizure and NLV system further improved this protection at the same dose. In MES acute model, safranal markedly increased the electroconvulsive threshold, where NLV further improved its effect. In PTZ chronic seizure model, NLV carried safranal significantly delayed the kindling rate of progress and the time it took to reach generalized seizures as compared to NLV control group. In conclusion, this study indicates that safranal inhibits generalized seizure in acute and chronic epilepsy models in mice and NLV can enhance this effect. So, NLV carried safranal may have potential value in treatment of generalized epilepsy.
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Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/uso terapêutico , Cicloexenos/administração & dosagem , Cicloexenos/uso terapêutico , Epilepsia Generalizada/tratamento farmacológico , Terpenos/administração & dosagem , Terpenos/uso terapêutico , Animais , Convulsivantes , Relação Dose-Resposta a Droga , Composição de Medicamentos , Eletroencefalografia , Eletrochoque , Epilepsia Generalizada/induzido quimicamente , Excitação Neurológica/efeitos dos fármacos , Lipídeos/química , Masculino , Camundongos , Tamanho da Partícula , Veículos Farmacêuticos , PilocarpinaRESUMO
AIMS: Abnormal intravesical pressure results in a series of pathological changes. We investigated the effects of hydrostatic pressure and muscarinic receptors on the release of inflammatory cytokines in rat and human bladder smooth muscle cells (HBSMCs). METHODS: Animal model of bladder outlet obstruction was induced by urethra ligation. HBSMCs were subjected to elevated hydrostatic pressure and/or acetylcholine (Ach). Macrophage infiltration in the bladder wall was determined by immunohistochemical staining. The expression of inflammatory genes was measured by RT-PCR, ELISA and immunofluorescence. RESULTS: In obstructed bladder, inflammatory genes and macrophage infiltration were remarkably induced. When HBSMCs were subjected to 200-300 cm H2 O pressure for 2-24 h in vitro, the expressions of IL-6 and RANTES were significantly increased. Hydrostatic pressure promoted the protein levels of phospho-NFκB p65 and phospho-ERK1/2 as well as muscarinic receptors. Moreover, NFκB or ERK1/2 inhibitors suppressed pressure-induced inflammatory genes mRNA. When cells were treated with 1 µM acetylcholine for 6 h, a significant increase in IL-6 mRNA expression was detected. Acetylcholine also enhanced pressure-induced phospho-NFκB p65 and IL-6 protein expression. Additionally, pressure-induced IL-6 was partially suppressed by muscarinic receptors antagonists. CONCLUSIONS: Hydrostatic pressure and muscarinic receptors were involved in the secretion of inflammatory cytokines in HBSMCs, indicating a pro-inflammatory effect of the two factors in the pathological process of BOO.
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Citocinas/metabolismo , Pressão Hidrostática , Miócitos de Músculo Liso/metabolismo , Receptores Muscarínicos/metabolismo , Obstrução do Colo da Bexiga Urinária/metabolismo , Acetilcolina/farmacologia , Animais , Doença , Feminino , Humanos , Antagonistas Muscarínicos/farmacologia , Miócitos de Músculo Liso/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Fator de Transcrição RelA/metabolismoRESUMO
Due to rapid urbanization and the scarcity of land, most of the urban parks and squares in cities are built close to major roads or industrial areas, where they are subject to many potential pollution sources, including vehicle exhaust and industrial emissions. The aims of this study were to determine the concentrations of selected metals (Pb, Cr, Cu, Ni, Zn, and Cd) in road dusts collected in urban parks and squares in Changchun, China, on June 1, 2013 (International Children's Day) and to estimate the pollution sources. The mean Pb, Cr, Cu, Ni, Zn, and Cd contents (70.89, 60.30, 43.56, 23.16, 170.80, and 0.3111 mg kg(-1) dry weight, respectively) in urban dusts were higher than their corresponding natural background values, particularly Pb, Cu, Zn, and Cd, which had about 2.5, 1.4, 1.9, and 2.6-fold higher levels, respectively. The results of principal component analysis indicated that Cr and Ni concentrations were mainly of natural origin, while Pb, Cu and Zn were derived from anthropogenic activities, and Cd tended to be from both sources. The geoaccumulation index (I geo) of these metals in the urban dusts under study indicates that they are uncontaminated with Cr and Ni; uncontaminated to moderately contaminated with Cu and Zn; and moderately contaminated with Pb and Cd. In addition, five particle sizes were analyzed separately for heavy metal concentrations. In all studied areas, there are large differences in the metal-loading percentage of different particle-size fractions among the samples, and the particles in 250-2,000-µm fraction are dominant in the total metal loading.
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Poeira/análise , Monitoramento Ambiental , Metais Pesados/análise , Logradouros Públicos/estatística & dados numéricos , Poluentes do Solo/análise , China , Cidades/estatística & dados numéricos , Poluição Ambiental/análise , Indústrias , Tamanho da Partícula , Emissões de VeículosAssuntos
Eritema/patologia , Incontinência Pigmentar/genética , Incontinência Pigmentar/patologia , Dermatopatias Vesiculobolhosas/patologia , Biópsia por Agulha , Diagnóstico Diferencial , Eritema/diagnóstico , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Incontinência Pigmentar/diagnóstico , Recém-Nascido , Monitorização Fisiológica/métodos , Dermatopatias Vesiculobolhosas/diagnóstico , Fatores de TempoRESUMO
Introduction Primary extramammary Paget's disease (EMPD) is a rare neoplasm that manifests as well-defined erythematous plaques, often misdiagnosed due to its similarity with different dermatoses. It may exhibit invasive features, involving adnexal invasions. The study aims to assess and compare the clinicopathological correlation of primary EMPD with adnexal features. Materials and methodology The monocentric observational retrospective study observed 43 confirmed primary EMPD cases in patients aged 45-95, excluding those with infectious dermatoses, pseudo-tumors, secondary lesions, or survived less than a month. Demographical, clinical and pathological observations were recorded. Expert dermatopathologists, blinded to the initial diagnosis, conducted a comprehensive histopathological evaluation yielding differential pathological diagnosis. Statistical analysis involved Pearson's Chi-square, Mann-Whitney U, and Spearman's Correlations for clinicopathological concordance and adnexal features. Recurrence was evaluated using Kaplan-Meier and log-rank tests, while multivariate recurrence analyses include Cox regression. A p-value < 0.05 was deemed significant. Results There was a significant association between adnexal involvement and the site of lesion (p < 0.05). There was a significant association (p < 0.05) between involved adnexal depth and primary EMPD subtypes. Adnexal involvement has a significant association with the concordance rates derived from clinicopathological correlations (p < 0.05). Smaller lesions and non-invasive EMPD significantly predict longer recurrence onset (p < 0.01). The primary EMPD subtype was the only independent predictor for recurrence time using the Cox regression model. Conclusion Adnexal proliferation in primary EMPD is considered vital on clinicopathological correlations and recurrence predictions, suggestive of its utility on both diagnosis and prognosis.
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This case report presents a rare instance of Eruptive Pruritic Papular Porokeratosis (EPPP) in a 71-year-old Chinese male, emerging on atypical sites (face, scalp, and ears) following a COVID-19 infection, and explores the potential link between viral infections and EPPP onset. The patient's lesions, characterized by annular brown patches with hyperkeratotic ridges, showed significant improvement following treatment with Baricitinib and Acitretin. This case underscores the need for awareness of unusual presentations of EPPP and suggests the potential efficacy of Janus Kinase (JAK) inhibitors in treatment, prompting further research into the pathophysiological connections between EPPP and viral infections. Adherence to the SCARE 2023 guidelines ensures a comprehensive and transparent case presentation.
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BACKGROUND: Lower limb deep vein thrombosis (DVT) concurrent with pulmonary embolism (PE) is perilous, particularly in the elderly, exhibiting heterogeneity with thrombophilia mutations. Tailored treatment is essential, yet sudden deaths complicate causative factor elucidation. This report emphasizes genetic testing necessity in PE patients with thrombophilia indicators, facilitating cause identification, personalized treatment guidance, and family education. CASE PRESENTATION: This study details a 75-year-old Chinese woman with DVT and PE, where genetic testing identified thrombophilia, guiding personalized treatment decisions. RESULTS: Upon admission, the patient, after over 10 days of bed rest, presented chest tightness, shortness of breath, and unilateral leg swelling. Diagnostic measures revealed DVT and a substantial PE. Genetic testing identified a PROS1 gene C200A>C mutation, reducing protein S activity. Following 2 weeks of anticoagulation and inferior vena cava filter insertion, the patient, discharged, initiated lifelong anticoagulant therapy. A 1-year follow-up showed no recurrent thrombotic events. Family members carrying the mutation received informed and educational interventions. CONCLUSION: Genetic testing for thrombophilic predisposition post-PE is crucial, elucidating etiology, guiding individualized treatment, and playing a pivotal role in family education.
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Deficiência de Proteína S , Embolia Pulmonar , Trombose , Filtros de Veia Cava , Trombose Venosa , Feminino , Humanos , Idoso , Deficiência de Proteína S/complicações , Deficiência de Proteína S/genética , Embolia Pulmonar/genética , Embolia Pulmonar/complicações , Trombose Venosa/genética , Trombose Venosa/complicações , Trombose/complicações , Mutação , Filtros de Veia Cava/efeitos adversosRESUMO
Key Clinical Message: Unlike most cases, the lesions were localized to the dorsum of the hand, lacked pruritus (itching), and did not exhibit "sperm-like blood vessels," which are typically pathognomonic to classical MF. Abstract: The study presents a rare case involving a 44-year-old woman who developed a skin condition on the base of her left thumb. Initially misdiagnosed as pigmented purpura, the need for further investigation arose to determine the nature of the condition accurately. The medical evaluation encompassed a comprehensive analysis of the patient's skin ailment. A series of diagnostic examinations were conducted to ascertain the underlying cause. Although routine blood tests yielded unremarkable results, the distinct characteristics of the rash prompted a more thorough investigation. Subsequent assessment revealed that the skin condition was not pigmented purpura, as initially presumed, but rather a manifestation of cutaneous T-cell lymphoma (CTCL) known as mycosis fungoides (MF). MF is an infrequent lymphoma predominantly affecting individuals aged 45-65, exhibiting a male-to-female sex ratio of 2:1. The annual incidence of MF ranges from 0.3 to 0.96 cases per 100,000 individuals. The woman's skin exhibited discrete patches adorned with colored dots, progressively thickening and pigmentation. Notably, the absence of pruritus did not dispel suspicion. This case underscores the significance of accurately diagnosing uncommon dermatological disorders to facilitate appropriate medical intervention. The unique appearance of the rash and its distinctive features, despite normal blood results, enabled the identification of MF. The patient's treatment encompassed a combination of steroids and narrowband UV therapy. Vigilance, continued research, and heightened awareness are paramount for early intervention and improved patient outcomes. Such efforts contribute to an enhanced understanding of the complexities of this condition.
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Quantitative estimation of groundwater recharge is crucial for limited water resources management. A combination of isotopic and chemical indicators has been used to evaluate the relationship between surface water, groundwater, and rainfall around the riparian of the Yellow River in the North China Plain (NCP). The ion molar ratio of sodium to chloride in surface- and groundwater is 0.6 and 0.9, respectively, indicating cation exchange of Ca(2+) and/or Mg(2+) for Na(+) in groundwater. The δD and δ(18)O values in rainfall varied from -64.4 to -33.4 and from -8.39 to -4.49. The groundwater samples have δD values in the range of -68.7 to -58.0 and δ(18)O from -9.29 to -6.85. The δ(18)O and δD in surface water varied from -8.51 to -7.23 and from -64.42 to -53.73. The average values of both δD and δ(18)O from surface water are 3.92 and 0.57, respectively, higher compared to groundwater. Isotopic composition indicated that the groundwater in the riparian area of the Yellow River was influenced by heavy rainfall events and seepage of surface water. The mass balance was applied for the first time to estimate the amount of recharge, which is probably 6% and 94% of the rainfall and surface water, respectively.
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Água Subterrânea , Algoritmos , China , Condutividade Elétrica , Concentração de Íons de Hidrogênio , Hidrologia , Isótopos de Oxigênio , Chuva , RiosRESUMO
For this study, 34 water samples were collected along the Wei River and its tributaries. Multivariate statistical analyses were employed to interpret the environmental data and to identify the natural and anthropogenic trace metal inputs to the surface waters of the river. Our results revealed that Zn, Se, B, Ba, Fe, Mn, Mo, Ni and V were all detected in the Wei River. Compared to drinking water guidelines, the primary trace metal pollution components (B, Ni, Zn and Mn) exceeded drinking water standard levels by 47.1, 50.0, 44.1 and 26.5%, respectively. Inter-element relationships and landscape features of trace metals conducted by hierarchical cluster analysis (HCA) identified a uniform source of trace metals for all sampling sites, excluding one site that exhibited anomalous concentrations. Based on the patterns of relative loadings of individual metals calculated by principal component analysis (PCA), the primary trace metal sources were associated with natural/geogenic contributions, agro-chemical processes and discharge from local industrial sources. These results demonstrated the impact of human activities on metal concentrations in the Wei River.
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Metais/análise , Rios/química , Poluentes Químicos da Água/análise , Poluição Química da Água/análise , China , Análise por Conglomerados , Análise MultivariadaRESUMO
We investigated whether human umbilical vein endothelial cells (HUVECs) under hypoxic conditions can suppress the production of cytokines in Hut-78 cells via the HIF-1α/PD-L1/PD-1 pathway, and the intervention effect of Nivolumab. HUVECs and HuT-78 cells were monocultured or cocultured in a tri-gas incubator with or without Nivolumab pretreatment. Real-time PCR, western blotting, and protein chips were used. Transcriptional regulation of PD-L1 and PD-1 by HIF-1α was analyzed by ChIP-qPCR and luciferase reporter gene assays. Apoptosis was assessed by flow cytometry. In HuT-78 cells, hypoxic monoculture significantly increased the expression of HIF-1α, PD-1, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, IFN-α, and Bax, decreased the expression of Bcl-2, and resulted in increased apoptosis. In comparison to hypoxic monoculture, hypoxic coculture significantly reduced the expression of IL-2, IL-4, IL-6, IL-8, IL-10, TNF-α, and IFN-α, as well as Bcl-2, in HuT-78 cells. Meanwhile, Bax expression was significantly increased with elevated apoptosis in HuT-78 cells. However, pretreatment with Nivolumab significantly antagonized the reduction in cytokines and the elevation in apoptosis in HuT-78 cells. Chip-qPCR and luciferase reporter gene assays demonstrated that hypoxia significantly increased the binding of HIF-1α to the upstream regulatory regions of PD-1 at -63 and -66 bp and PD-L1 at -571 bp, promoting their transcription. Therefore, HUVECs under hypoxia can reduce cytokine production and inhibit their own apoptosis in co-culture with HuT-78 cells via the HIF-1α/PD-L1/PD-1 pathway. These findings provide new clues for exploring the combined use of immune checkpoint inhibitors and anti-angiogenic drugs in clinical settings.
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Interleucina-10 , Receptor de Morte Celular Programada 1 , Humanos , Células Endoteliais da Veia Umbilical Humana , Interleucina-10/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Interleucina-8/metabolismo , Nivolumabe , Interleucina-2/metabolismo , Interleucina-4/metabolismo , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Proteína X Associada a bcl-2/metabolismo , Apoptose , Hipóxia Celular , Hipóxia/metabolismo , Luciferases/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismoRESUMO
Lateral retinacular release of the patella is the main surgical treatment for excessive lateral pressure syndrome. It was first described by Merchant and Mercer in 1974. The main complications of arthroscopic lateral retinacular release are hemarthrosis and medial patellar instability. The main causes of these complications are the disturbance of the synovial membrane of the joint capsule and excessive release of the lateral retinaculum. In this article, we introduce a method for arthroscopic lateral retinacular release that maintains the overall structure of the joint capsule: capsule-uncut immaculate (CUI) lateral retinacular release.
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Mid-dermal elastolysis (MDE) is a very rare and acquired skin condition. MDE has a variety of clinical manifestations that can be presented with a reticular erythematous patch with telangiectasis, perifollicular popular protrusions, or finely wrinkled skin. A biopsy is always necessary to rule out other potential elastic fiber disorders. In this case study, a 33-year-old female with an odd MDE presentation in her neck area is examined. No contributing factors, apart from exposure to sunlight, could be gleaned from the patient's history. The patient didn't benefit from the application of various types of topical agents or any other therapies to lessen the size and advancement of the lesion. In this distinct case, we discuss clinical and histological findings and the treatment plan offered, as well as include a concise review of specific past literature.
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For patients undergoing radical cystectomy with standard lymphadenectomy for bladder cancer, appropriate urinary diversion (with a pouch and conduit) improves postoperative quality of life, reduces postoperative complications, and prolongs survival. We developed a novel heterotopic ileal reservoir to achieve these goals. This report describes the methodology involved and the incidence of intraoperative and postoperative complications. Three patients who underwent novel heterotopic ileal reservoir creation following radical cystectomy and standard lymphadenectomy (for bladder cancer) were evaluated. The ileum served as a pouch in which the ureters and appendix were implanted by extramural tunnelling. The appendix served as a conduit and pelvic reperitonealization was performed. Operative times, intraoperative blood loss, time to intestinal function recovery, incidence of intestinal obstruction and ureteric reflux, and bladder volumes and continence levels were evaluated. The surgical intervention was successful with operation times ranging 410-525â min, blood loss ranging 300-700â ml, and recovery time for intestinal function ranging 3-5 days. The postoperative hospitalization time was 11-15 days. Subileus occurred in patient B, who recovered after fasting and fluid replacement. Patients B and C achieved complete continence 6 weeks after surgery, while patient A experienced umbilical urine leakage with catheterization time intervals that exceeded 4â h. At 3 months after surgery, the bladder capacities of all patients ranged 250-370â ml. Follow-up cystography suggested the presence of bilateral ureteral reflux in patient A, with mild and moderate reflux on the left right sides, respectively. All patients achieved complete continence. Patients were followed for 3-9 months postoperatively; chest and abdominal computed tomography and cystography showed absence of hydronephrosis, recurrence, or distant metastasis during this period. The novel heterotopic continent ileal reservoir described in this study may be suitable for selected patients. The surgical procedure is safe when performed by well-trained and highly experienced urologists.
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BACKGROUND: Deep brain stimulation of the subthalamic nucleus (STN-DBS) is an effective treatment for patients with advanced Parkinson's disease, the outcome of this surgery is highly dependent on the accurate placement of the electrode in the optimal target of STN. PURPOSE: In this study, we aim to develop a target localization pipeline for DBS surgery, considering that the heart of this matter is to achieve the STN and red nucleus segmentation, a deep learning-based automatic segmentation approach is proposed to tackle this issue. METHODS: To address the problems of ambiguous boundaries and variable shape of the segmentation targets, the hierarchical attention mechanism with two different attention strategies is integrated into an encoder-decoder network for mining both semantics and fine-grained details for segmentation. The hierarchical attention mechanism is utilized to suppress irrelevant regions in magnetic resonance (MR) images while build long-range dependency among segmentation targets. Specifically, the attention gate (AG) is integrated into low-level features to suppress irrelevant regions in an input image while highlighting the salient features useful for segmentation. Besides, the self-attention involved in the transformer block is integrated into high-level features to model the global context. Ninety-nine brain magnetic resonance imaging (MRI) studies were collected from 99 patients with Parkinson's disease undergoing STN-DBS surgery, among which 80 samples were randomly selected as the training datasets for deep learning training, and ground truths (segmentation masks) were manually generated by radiologists. RESULTS: We applied five-fold cross-validation on these data to train our model, the mean results on 19 test samples are used to conduct the comparison experiments, the Dice similarity coefficient (DSC), Jaccard (JA), sensitivity (SEN), and HD95 of the segmentation for STN are 88.20%, 80.32%, 90.13%, and 1.14 mm, respectively, outperforming the state-of-the-art STN segmentation method with 2.82%, 4.52%, 2.56%, and 0.02 mm respectively. The source code and trained models of this work have been released in the URL below: https://github.com/liuruiqiang/HAUNet/tree/master. CONCLUSIONS: In this study, we demonstrate the effectiveness of the hierarchical attention mechanism for building global dependency on high-level semantic features and enhancing the fine-grained details on low-level features, the experimental results show that our method has considerable superiority for STN and red nucleus segmentation, which can provide accurate target localization for STN-DBS.
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Estimulação Encefálica Profunda , Doença de Parkinson , Núcleo Subtalâmico , Humanos , Núcleo Subtalâmico/diagnóstico por imagem , Núcleo Subtalâmico/patologia , Núcleo Subtalâmico/fisiologia , Estimulação Encefálica Profunda/métodos , Doença de Parkinson/diagnóstico por imagem , Doença de Parkinson/terapia , Imageamento por Ressonância Magnética , SoftwareRESUMO
Zernike polynomials are commonly used to describe the aberration of light beams, and the beam quality of Gaussian beams with aberrations can be deduced when the order of Zernike polynomials is limited. In this paper, Hermite polynomials are utilized to reconstruct the aberrations of Gaussian beams. The beam quality factor is directly related to the coefficient and terms of Hermite polynomials and has no limit on its index. We analyzed the beam quality of a Gaussian beam with a quartic aberration and other former 11th Zernike aberrations by Hermite polynomial expansion. The result corresponds with the published research work.
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Metabolic-associated fatty liver disease (MAFLD) is becoming more common due to lifestyle changes. A long-term high-fat and high-glucose diet induces glycolipid metabolism disorders in the liver, which results in the development of MAFLD. To date, there is no specific clinically useful therapeutics for this disease. Natural products or synthetic compounds were screened and investigated to find effective agents for treating MAFLD. In this study, nootkatone (Nok), a natural sesquiterpene ketone isolated from Alpiniae oxyphyllae fructus, was explored for its potential to treat MAFLD, and underlying mechanisms were studied. Our results show that Nok dramatically ameliorated the disordered lipid and glucose metabolism in MAFLD mice, decreased fat accumulation in hepatic tissue, and improved liver injury. Inflammation, metabolic disorder, and oxidative stress were ameliorated in liver tissue based on RNA-seq transcriptome comparison between a Nok-treated group and an MAFLD model group. Furthermore, Nok significantly activated AMPK activity and inhibited MAPK activity, especially the p38 and JNK signaling pathways, in vivo based on western blot analysis. The pharmaceutical effects and potential signaling pathways impacted by Nok were also investigated in L02 cells. Nok significantly promoted the consumption of glucose and decreased the deposition of triglycerides in vitro. The p-AMPKα level was notably upregulated by Nok, indicating dramatic AMPK activation. In addition, Nok decreased the levels of p-ERK1/2, p-p38, and p-JNK. Nok also inhibited the activation of MAPK signaling and, thus, alleviated MAFLD development. Our results suggest that Nok may be useful in treating MAFLD. Nok may ameliorate MAFLD by regulating glycolipid metabolism disorders by activating AMPK and inhibiting MAPK activity. Collectively, this study suggests that Nok is an effective compound for the treatment of MAFLD.
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Nonalcoholic fatty liver disease (NAFLD) is closely related to glycolipid metabolism and liver inflammation. And there is no effective drug approved for its clinical therapy. In this study, we focused on mangiferin (Man) and explored its effects and mechanisms on NAFLD treatment based on the regulation of glycolipid metabolism and anti-inflammatory in vivo and in vitro. The results exhibited that Man can significantly attenuate liver injury, insulin resistance, and glucose tolerance in high-fat diet- (HFD-) induced NAFLD mice and significantly reduce fat accumulation and inflammation in hepatic tissue of NAFLD mice. The transcriptome level RNA-seq analysis showed that the significantly different expression genes between the Man treatment group and the HFD-induced NAFLD model group were mainly related to regulation of energy, metabolism, and inflammation in liver tissue. Furthermore, western blots, real-time PCR, and immunohistochemistry experiments confirmed that Man significantly activated the AMPK signal pathway and inhibited NLRP3 inflammasome activation and pyroptosis in NAFLD mice. In in vitro cell experiments, we further confirmed that Man can promote glucose consumption and reduce intracellular triglyceride (TG) accumulation induced by free fatty acids in HepG2 cells and further that it can be blocked by AMPK-specific inhibitors. Western blot results showed that Man upregulated p-AMPKα levels and exhibited a significant AMPK activation effect, which was blocked by compound C. At the same time, Man downregulated the expression of NLRP3 inflammasome-related proteins and inhibited the activation of NLRP3 inflammasome, alleviating cell pyroptosis and inflammation effects. These results indicate that Man anti-NAFLD activity is mediated through its regulation of glucolipid metabolism by AMPK activation and its anti-inflammatory effects by NLRP3 inflammasome inhibition. Our study indicates that Man is a promising prodrug for the therapy of NAFLD patients.
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Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Xantonas/farmacologia , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Dieta Hiperlipídica , Modelos Animais de Doenças , Células Hep G2 , Humanos , Inflamassomos/antagonistas & inibidores , Inflamassomos/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/imunologia , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/patologia , Masculino , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/patologia , Piroptose/efeitos dos fármacos , Piroptose/imunologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/imunologia , Xantonas/uso terapêuticoRESUMO
INTRODUCTION: This protocol is for a meta analysis that aims to systematically review the diagnostic value of anti-hepatitis B virus in serum tested by the enzyme linked immunosorbent assay in patients with hepatitis B. METHODS AND ANALYSIS: The following electronic databases will be searched from inception to Mar 2021: PubMed, Web of Science, ScienceDirect, EMBASE, MEDLINE, Springer, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, VIP Chinese Science and Technology Periodical Database, and Wanfang Database. All study about enzyme linked immunosorbent assay reagents have been published at home and abroad to diagnose hepatitis B virus will be included. MetaDisc 1.4 soft will used to calculate pooled effect size in sensitivity, specifi city, likelihood ratio, diagnostic odds ratio and summary receiver operating characteristic curve, and area under the curve as well. ETHICS AND DISSEMINATION: Formal ethical approval is not required, as the data are not individualized. The findings of this systematic review will be disseminated in a peer-reviewed publication and/or presented at relevant conferences. REGISTRATION NUMBER: INPLASY2020100051.
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Protocolos Clínicos , Vírus da Hepatite B/imunologia , Hepatite B/enzimologia , Ensaio de Imunoadsorção Enzimática/métodos , Vírus da Hepatite B/patogenicidade , Humanos , Metanálise como Assunto , Revisões Sistemáticas como AssuntoRESUMO
The novel coronavirus disease 2019 (COVID-19) is a global epidemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). SARS-CoV-2 has a similar structure to severe acute respiratory syndrome coronavirus-1(SARS-CoV-1). The S protein on the surface of the virus is cleaved by host proprotein convertases (PCs) to expose the active N-terminal S1 extracellular domain. Its receptors are angiotensin-converting enzyme 2 (ACE2), and the C-terminal S2 membrane anchoring protein is responsible for translocating the virus into the cell. Among patients with COVID-19, there is a higher prevalence of cardiovascular disease, and more than 7% of patients have suffered myocardial damage due to the infection, but the internal mechanism is still poorly understood. There is currently no specific and effective targeted treatment. Reduction of the patient's morbidity and mortality is an urgent problem that needs to be solved clinically. By exploring the theoretical analysis of PCs and ACE2 in COVID-19 cardiovascular susceptibility, some insights on how to prevent and alleviate adverse cardiovascular prognosis have been provided in this study.