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A series of x%Ho3+, 5 %Tm3+, y%Yb3+:Bi2WO6 (x = 0, 0.5, 1, 3, 5; y = 0.5, 1, 3) luminescent materials was prepared using a high-temperature solid-phase method. The microstructure, up-conversion luminescence, and temperature sensing properties of the synthesized powders were analyzed. X-ray diffraction patterns revealed that doping with Ho3+, Tm3+, and Yb3+ ions at certain concentrations did not affect the orthorhombic crystal structure of the Bi2WO6 host. Scanning electron microscopy revealed that the morphology of the sample consisted of lumpy particles with a particle size range of 1-5 µm and agglomeration. SEM mapping and energy-dispersive X-ray spectroscopy analyses revealed that each element was relatively uniformly distributed on the particle surface. Under 980 nm excitation (380 mW), the strongest luminescence of the sample was obtained when both Ho3+ and Yb3+ doping concentrations were 1 %. Compared with the luminescence of the 5 %Tm3+ and 1 %Yb3+:Bi2WO6 sample, with increasing Ho3+ concentrations, the luminescence intensity of Tm3+ was first enhanced and subsequently weakened, whereas the luminescence of Ho3+ was significantly weakened, which indicates the positive energy transfer from Ho3+ â Tm3+. At 980 nm (80-380 mW), for the 1 %Ho3+, 5 %Tm3+, and 1 %Yb3+:Bi2WO6 sample, the 538 nm, 545 nm, 660 nm, and 804 nm emission peaks originated from the two-photon absorption. FIR660 nm/804 nm, FIR545 nm/804 nm, and FIR538 nm/804 nm were used to characterize the temperature and corresponded to temperature sensitivities Sr of 0.0046 K-1, 0.022 K-1 and 0.024 K-1 at 573 K, respectively. At 498 K, the minimum temperature resolution δT values were 0.03384 K, 0.03203 K and 0.04373 K. When the temperature increased from 298 K to 573 K, the powder sample luminescence gradually shifted from the yellow-green region to the red region. The results of environmental discoloration and thermochromic performance tests indicate that this sample has potential application in optical anti-counterfeiting. FIR804 nm /660 nm and FIR804 nm /538 nm were obtained for the 40 NTU turbidity suspension under identical excitation conditions. At 298 K, for the 40 NTU turbidity sample, the maximum Sr values were 0.0197 K-1 and 0.0405 K-1; at 340 K, the minimum temperature resolutions δT values were 0.54037 K and 0.66237 K. When the temperature decreased from 340 K to 298 K, the luminescence of the 40 NTU suspension samples gradually shifted from the yellow region to the green region.
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Fungal keratitis (FK) is a blinding corneal infectious disease. The prognosis is frequently unfavorable due to fungal invasion and an excessive host inflammatory response. Licochalcone A (Lico A) exhibits a broad spectrum of pharmacological activities, encompassing antifungal, anti-inflammatory, antioxidation, and antitumor properties. However, the role of Lico A has not yet been studied in FK. In this study, we discovered that Lico A could disrupt Aspergillus fumigatus (A. fumigatus) biofilms, inhibit fungal growth and adhesion to host cells, induce alterations of hyphal morphology, and impair the cell membrane and cell wall integrity and mitochondrial structure of A. fumigatus. Lico A can alleviate the severity of FK in mice, reduce neutrophil infiltration and fungal load, and significantly decrease the pro-inflammatory cytokines in mouse corneas infected with A. fumigatus. In vitro, we also demonstrated that Lico A increased the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) around the nucleus in human corneal epithelial cells (HCECs) stimulated with A. fumigatus. We verified that the anti-inflammatory effect of Lico A is associated with the activation of the Nrf2/HO-1 axis. These results indicated that Lico A could provide a protective role in A. fumigatus keratitis through its anti-inflammatory and antifungal activities.
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PURPOSE: This study aims to assess stone-free rates after flexible ureterorenoscopy (fURS) using the T.O.HO. (Tallness, Occupied lesion, Hounsfield unit evaluation) scoring system and Ito's nomogram. MATERIALS AND METHODS: In the study conducted with 484 patients, the following parameters were analyzed: age, sex, comorbidities, hospitalization, affected side, extracorporeal shock wave lithotripsy (ESWL) history, stone length, stone density, number of stones, location, and presence of hydronephrosis. RESULTS: Multivariate logistic regression analysis revealed that stone length, stone number, and lower pole stone location were associated with the prediction of stone-free status. The cut-off value for Ito's score was determined to be 13.5 points, with an AUC of 0.792 (sensitivity, 0.609; specificity, 0.821) and a 95% confidence interval of (0.752-0.832) (Fig. 1). The cutoff for the T.O.HO. score was 6.5 points, with an AUC of 0.744 (sensitivity 0.738, specificity 0.602) and a 95% confidence interval of (0.699-0.789). CONCLUSION: In conclusion, T.O.HO. scoring system and the Ito's nomogram are promising tools to predict stone-free status (SFS) after fURS in preoperative evaluation. In addition, the success of scoring systems in predicting SFS preoperatively appears promising and offers a potentially valuable approach.
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Cálculos Renales , Nomogramas , Ureteroscopía , Humanos , Ureteroscopía/métodos , Femenino , Masculino , Persona de Mediana Edad , Cálculos Renales/cirugía , Adulto , Anciano , Estudios Retrospectivos , UreteroscopiosRESUMEN
Liver ischemia-reperfusion (I/R) injury is a detrimental complication of organ transplantation, shock, and sepsis. However, the available drugs to mitigate I/R injury remain limited. Jujuboside A (JuA) is renowned for its antioxidant, anti-inflammatory, and anti-apoptotic properties; nevertheless, its potential in liver I/R injury remains unknown. Thus, this study aimed to explore the role and underlying mechanisms of JuA in liver I/R injury. Mouse models of I/R and AML12 cell models of hypoxia/reoxygenation (H/R) were constructed. Haematoxylin and eosin staining, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) detection, and cell viability analysis were used to assess liver injury. To evaluate oxidative stress, inflammation, apoptosis, and mitochondrial damage, immunofluorescence staining, transmission electron microscopy analysis, enzyme-linked immunosorbent assay, and flow cytometry were conducted. Moreover, molecular docking techniques and western blot were employed to identify downstream target molecules and pathways affected by JuA. The results showed that JuA pretreatment effectively attenuated liver necrosis and ALT and AST level elevations induced by I/R while enhancing AML12 cell viability following H/R. Furthermore, JuA pretreatment suppressed oxidative stress triggered by I/R and H/R, thereby inhibiting the level of pro-inflammatory factors and NLRP3 inflammasome activation. Notably, JuA pretreatment alleviated mitochondrial damage and apoptosis. Mechanistically, JuA pretreatment resulted in the activation of the AKT/NRF2/HO-1 signalling pathways, whereas MK2206, the inhibitor of AKT, partially reversed the hepatoprotective effects of JuA during liver I/R. Collectively, our findings illustrated that JuA mitigated oxidative stress, inflammation, apoptosis, and mitochondrial damage by facilitating the AKT/NRF2/HO-1 signalling pathway, thereby alleviating liver I/R injury.
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Apoptosis , Hígado , Factor 2 Relacionado con NF-E2 , Proteínas Proto-Oncogénicas c-akt , Daño por Reperfusión , Transducción de Señal , Animales , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Daño por Reperfusión/tratamiento farmacológico , Factor 2 Relacionado con NF-E2/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratones , Transducción de Señal/efectos de los fármacos , Masculino , Hígado/patología , Hígado/metabolismo , Hígado/efectos de los fármacos , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Ratones Endogámicos C57BL , Hemo-Oxigenasa 1/metabolismo , Línea Celular , Proteínas de la Membrana/metabolismo , Hemo Oxigenasa (Desciclizante)/metabolismoRESUMEN
BACKGROUND: Bone loss caused by microgravity exposure presents a serious threat to the health of astronauts, but existing treatment strategies have specific restrictions. This research aimed to investigate whether salidroside (SAL) can mitigate microgravity-induced bone loss and its underlying mechanism. METHODS: In this research, we used hindlimb unloading (HLU) and the Rotary Cell Culture System (RCCS) to imitate microgravity in vivo and in vitro. RESULTS: The results showed that salidroside primarily enhances bone density, microstructure, and biomechanical properties by stimulating bone formation and suppressing bone resorption, thereby preserving bone mass in HLU rats. In MC3T3-E1 cells cultured under simulated microgravity in rotary wall vessel bioreactors, the expression of osteogenic genes significantly increased after salidroside administration, indicating that salidroside can promote osteoblast differentiation under microgravity conditions. Furthermore, the Nrf2 inhibitor ML385 diminished the therapeutic impact of salidroside on microgravity-induced bone loss. Overall, this research provides the first evidence that salidroside can mitigate bone loss induced by microgravity exposure through stimulating the Nrf2/HO-1 pathway. CONCLUSION: These findings indicate that salidroside has great potential for treating space-related bone loss in astronauts and suggest that Nrf2/HO-1 is a viable target for counteracting microgravity-induced bone damage.
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Glucósidos , Factor 2 Relacionado con NF-E2 , Fenoles , Simulación de Ingravidez , Glucósidos/farmacología , Glucósidos/uso terapéutico , Animales , Fenoles/farmacología , Fenoles/uso terapéutico , Factor 2 Relacionado con NF-E2/metabolismo , Ratones , Simulación de Ingravidez/efectos adversos , Ratas , Masculino , Hemo-Oxigenasa 1/metabolismo , Ratas Sprague-Dawley , Transducción de Señal/efectos de los fármacos , Ingravidez/efectos adversos , Osteogénesis/efectos de los fármacos , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Suspensión Trasera , Resorción Ósea/prevención & control , Resorción Ósea/etiología , Resorción Ósea/metabolismo , Densidad Ósea/efectos de los fármacos , Proteínas de la MembranaRESUMEN
OBJECTIVE: Rheumatoid arthritis (RA) is a common chronic autoimmune inflammatory disease. The pathogenesis of RA is complex, and RA lacks effective therapeutic drugs. Heme oxygenase 1 (HO-1) is found to be reduced in RA. However, the role of HO-1 in RA and related mechanisms have not been elucidated. METHODS: RA rat model was established. The expression of HO-1 was upregulated by hemin. The increase weight rate, the degree of toe swelling, and the arthritis index were analyzed to evaluate the therapeutic effect of HO-1 on RA. In vitro RAW264.7 inflammatory cell model was established using 5 ng/mL IL-1. SnPP or hemin were used to inhibit or upregulate HO-1 expression. Tetrazolium salt colorimetric assay (MTT) was selected to test cell proliferation. ELISA was used to determine the concentrations of cellular inflammatory factors IL-1 and IL-6. Reactive oxygen species (ROS) activity was assessed. Western blot was performed to analyze NF-[Formula: see text]B and MMP-3 expressions. RESULTS: The expression of HO-1 was decreased in RA rats, and hemin increased HO-1 level in arthritic rats, which elevated the increase weight rate and decreased toe swelling degree and arthritis index (P<0.05). Hemin significantly upregulated HO-1 expression, inhibited inflammatory cell proliferation, decreased IL-1 and IL-6 expressions, declined ROS level, restrained NF-[Formula: see text]B expression, and enhanced MMP-3 expression in Raw264.7 cells induced by LPS (P<0.05). SnPP obviously inhibited the expression of HO-1, promoted cell proliferation, elevated IL-1 and IL-6 secretions, increased ROS level, promoted NF-[Formula: see text]B expression, and decreased MMP-3 level compared with LPS group (P<0.05). CONCLUSION: Upregulation of HO-1 can improve arthritis symptoms by reducing ROS expression, inhibiting NF-[Formula: see text]B signaling pathway, elevating MMP-3 expression, attenuating inflammatory factor secretion, and suppressing inflammatory cell proliferation.
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Artritis Reumatoide , Hemo-Oxigenasa 1 , Hemina , Especies Reactivas de Oxígeno , Animales , Artritis Reumatoide/patología , Artritis Reumatoide/metabolismo , Ratones , Células RAW 264.7 , Ratas , Hemo-Oxigenasa 1/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Hemina/farmacología , Interleucina-1/metabolismo , Modelos Animales de Enfermedad , Inflamación/patología , Inflamación/metabolismo , Masculino , Proliferación Celular/efectos de los fármacos , FN-kappa B/metabolismo , Metaloproteinasa 3 de la Matriz/metabolismo , Interleucina-6/metabolismo , Ratas Sprague-Dawley , Protoporfirinas/farmacología , Hemo Oxigenasa (Desciclizante)RESUMEN
Myocardial infarction (MI) is the primary source of death in cardiovascular diseases. Myricitrin (MYR) is a phenolic compound known for its antioxidant properties. This study aimed to investigate the impact of MYR alone or combined with exercise on a rat model of MI and its underlying mechanism. Sprague-Dawley rats were randomized into 5 groups: sham-operated (Sham), MI-sedentary (MI-Sed), MI-exercise (MI-Ex), MI-sedentary + MYR (MI-Sed-MYR) and MI-exercise + MYR (MI-Ex-MYR). MI was induced through ligation of left anterior descending coronary artery. The treatment with exercise or MYR (30 mg/kg/d) gavage began one week after surgery, either individually or in combination. After 8 weeks, the rats were assessed for cardiac function. Myocardial injuries were estimated using triphenyltetrazolium chloride, sirius red and Masson staining. Changes in reactive oxygen species (ROS) levels, mitochondrial membrane potential (ΔΨm), apoptosis and Nrf2/HO-1 pathway were analyzed by ROS kit, JC-1 kit, TUNEL assay, Western blot and immunohistochemistry. Both MYR and exercise treatments improved cardiac function, reduced infarct size, suppressed collagen deposition, and decreased myocardial fibrosis. Additionally, both MYR and exercise treatments lowered ROS production induced by MI, restored ΔΨm, and attenuated oxidative stress and apoptosis in cardiomyocytes. Importantly, the combination of MYR and exercise showed greater efficacy compared to individual treatments. Mechanistically, the combined intervention activated the Nrf2/HO-1 signaling pathway. These findings suggest that the synergistic effect of MYR and exercise may offer a promising therapeutic approach for alleviating MI.
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Irritable bowel syndrome (IBS) is a prevalent gastrointestinal dysfunction. Cimifugin is an active component of Radix saposhnikoviae which is effective for maintaining intestinal barrier integrity and intestinal function. This study aimed to investigate the treatment efficacy of Cimifugin on intestinal barrier dysfunction and to unveil the relevant mechanism through network pharmacology and experimental verification as well as molecular docking. Through SuperPred and Pubchem databases, the targets of Cimifugin were obtained. The disease targets were screened using Disgenet and GEO databases. With STRING database and Cytoscape software, the analysis of PPI network was performed. In DAVID database, the hub genes of Cimifugin were analyzed using GO and Pathway enrichment analyses. To validate the binding of Cimifugin with core targets, molecular docking was performed. The in vitro cellular model of intestinal barrier was established via the induction of Caco2 cells with LPS. TEER was used to detect epithelial barrier function and permeability was measured using FITC-dextran (FD4). Western blotting was used to measure the expressions of SIRT1, tight junction proteins, and NRF2/HO-1 signaling pathway-related proteins. The fluorescence intensity of ZO-1, Occludin, and Claudin-1 was detected using immunofluorescence staining. ELISA was used to detect the expression levels of inflammatory cytokines. Through the integration of all targets of IBS and Cimifugin, 94 frequent drug-disease-related targets were identified. These targets were enriched in some signaling pathways, like cellular responses to stress, cellular responses to stimuli, and VEGFA-VEGFR2. Ten hub genes including PTGS2, ANPRP, TGFB1, ACACA, SIRT1, NEF2L2, APEX1, IL6, AKT1, and HSP90AB1 were obtained. Cimifugin showed strong affinity with four key genes, including AKT1, SIRT1, IL6, and NFE2L2 (NRF2), which were obtained through the intersection of hug genes with cellular responses to stimuli. In vitro experiments showed that Cimifugin ameliorated LPS-induced intestinal barrier injury in Caco2 cells via upregulating SIRT1 to modulate NRF2/HO-1 signaling pathway. Cimifugin could alleviate intestinal barrier dysfunction in IBS by upregulating SIRT1 to regulate the NRF2/HO-1 signaling pathway.
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Pyroptosis induced by oxidative stress is a significant contributor to mental health disorders, including depression (+)-Catechin (CA), a polyphenolic compound prevalent in various food sources, has been substantiated by prior research to exhibit potent antioxidant properties and potential antidepressant effects. Nonetheless, the precise antidepressive mechanisms and effects of CA remain incompletely elucidated. In this study, we employed corticosterone (CORT) and PC12 cells to develop a cellular model of depression, aiming to investigate the protective effects of CA against CORT-induced cellular damage. Our objective was to elucidate the underlying mechanisms of protective action. We utilized transcriptomic analysis to identify differentially expressed genes and employed bioinformatics approaches to predict the potential mechanisms of CA's protective effects in PC12 cells. These transcriptomic predictions were subsequently validated through western blot analysis. The findings indicated that CA possesses the capacity to mitigate oxidative stress and suppress pyroptosis in PC12 cells via the activation of the PI3K/AKT signaling pathway. This activation subsequently modulates the Nrf2/HO1/NF-κB pathways, thereby providing protection to PC12 cells against damage induced by CORT. Furthermore, we investigated the interaction between CA and the Keap1 protein employing molecular docking and protein thermal shift assays. We propose that CA can activate Nrf2 through two mechanisms to decrease reactive oxygen species (ROS) levels and inhibit pyroptosis: one mechanism involves the activation of the PI3K/AKT signaling pathway, and the other involves direct binding to Keap1, leading to an increase in p-Nrf2.
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Retinal neovascular disease is a leading cause of vision loss and blindness globally. It occurs when abnormal new blood vessels form in the retina. In this study, we utilized tetrahedral framework nucleic acids (tFNAs) as vehicles to load quercetin (QUE), a small-molecule flavonoid, forming a deoxyribonucleic acid (DNA) nanocomplex, tFNAs-QUE. Our data show this nanocomplex inhibits pathological neovascularization, reduces the area of retinal nonperfusion area, protects retinal neurons, and preserves the visual function. Further, we discovered that tFNAs-QUE selectively upregulates the AKT/Nrf2/HO-1 signaling pathway, which can suppress pathological vascular growth and exert antioxidative effects. Therefore, this study presents a promising small-molecule-loading mechanism for the treatment of ischemic retinal diseases.
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This study investigates the composition characteristics and anti-inflammatory activity mechanisms of the essential oil from the leaves of Crossostephium chinense. C. chinense is a perennial herb commonly found in East Asia, traditionally used to treat various ailments. The essential oil extracted through water distillation, primarily contains 1,8-cineole (13.73%), santolina triene (13.53%), and germacrene D (10.67%). Three compounds were identified from the essential oil, namely 1-acetoxy-2-(2-hydroxypropyl)-5-methylhex-3,5-diene, 1-acetoxy-isopyliden-hex-5-en-4-one, and chrysanthemyl acetate, with the first two being newly discovered compounds. Then, the essential oil of C. chinense exhibits significant anti-inflammatory effects on RAW264.7 macrophages, effectively inhibiting the production of NO and ROS, with the IC50 value of 10.3 µg/mL. Furthermore, the essential oil reduces the expression of pro-inflammatory cytokines such as TNF-α, IL-6, and IL-1ß. Mechanistic studies indicate that the essential oil affects the inflammatory response by inhibiting the expression of iNOS but has no significant impact on COX-2. Further analysis suggests that the essential oil may regulate the inflammatory response through the ERK protein in the MAPK pathway and IκBα in the NF-κB pathway, while also promoting the activity of the NRF2/HO-1 antioxidant pathway, enhancing the cell's antioxidant capacity, thereby achieving an effect of inhibiting the inflammatory response. These results highlight the potential application value of C. chinense leaf essential oil in the medical and healthcare fields.
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Prostate cancer (PC) is a significant cause of mortality in men worldwide, hence the need for a comprehensive understanding of the molecular mechanisms underlying its progression and resistance to treatment. Heme oxygenase-1 (HO-1), an inducible enzyme involved in heme catabolism, has emerged as a critical player in cancer biology, including PC. This review explores the multifaceted role of HO-1 in PC, encompassing its function, regulation, and implications in cancer therapy. HO-1 influences cell proliferation, anti-apoptotic pathways, angiogenesis, and the tumor microenvironment, thereby influencing tumor growth and metastasis. HO-1 has also been associated with therapy resistance, affecting response to standard treatments. Moreover, HO-1 plays a significant role in immune modulation, affecting the tumor immune microenvironment and potentially influencing therapy outcomes. Understanding the intricate balance of HO-1 in PC is vital for developing effective therapeutic strategies. This review further explores the potential of targeting HO-1 as a therapeutic approach, highlighting challenges and opportunities. Additionally, clinical implications are discussed, focusing on the prognostic value of HO-1 expression and the development of novel combined therapies to augment PC sensitivity to standard treatment strategies. Ultimately, unraveling the complexities of HO-1 in PC biology will provide critical insights into personalized treatment approaches for PC patients.
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Hemo-Oxigenasa 1 , Neoplasias de la Próstata , Microambiente Tumoral , Humanos , Hemo-Oxigenasa 1/metabolismo , Hemo-Oxigenasa 1/genética , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/terapia , Neoplasias de la Próstata/genética , Masculino , Regulación Neoplásica de la Expresión Génica , Animales , Proliferación CelularRESUMEN
BACKGROUND AND PURPOSE: Skin flaps are among the most important means of wound repair in clinical settings. However, partial or even total distal necrosis may occur after a flap operation, with severe consequences for both patients and doctors. This study investigated whether tert-butylhydroquinone (TBHQ), a known agonist of the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), and an antioxidant, could promote skin flap survival. EXPERIMENTAL APPROACH: McFarlane skin flap models were established in male Sprague-Dawley rats and then randomly divided into control, low-dose TBHQ, and high-dose TBHQ treatment groups. On postoperative day 7, the survival and blood flow of the skin flaps were assessed. Using flap tissue samples, angiogenesis, inflammation, apoptosis, autophagy, and Nrf2/haem oxygenase 1 (HO-1) signalling pathway activity were measured with immunohistochemical techniques and western blotting. KEY RESULTS: TBHQ dose-dependently stimulated the Nrf2/HO-1 signalling pathway, inducing autophagy through the up-regulation of LC3B and beclin 1 and concurrently suppressing p62 expression. Additionally, TBHQ hindered apoptosis by enhancing Bcl-2 expression while inhibiting the expression of Bax. It suppressed inflammation by inhibiting the expression of interleukin 1ß, interleukin 6, and tumour necrosis factor-α and enhanced angiogenesis by promoting the expression of vascular endothelial growth factor. CONCLUSION AND IMPLICATIONS: In summary, TBHQ promoted flap survival in rats by up-regulating the Nrf2/HO-1 signalling pathway. As TBHQ is already widely used as a food additive, it could offer an acceptable means of improving clinical outcomes following skin flap surgery in patients.
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Objectives: Hepatic ischemia-reperfusion (HIR) is a severe process in pathophysiology that occurs clinically in hepatectomy, and hepatic transplantations. The present study aimed to investigate the effect of PKC θ deletion against HIR injury and elucidate its mechanism in pathophysiology. Materials and Methods: HIR injury was induced in wild-type and PKC θ deletion mice treated with or without heme. The ALT and AST levels were determined to evaluate liver function. HIR injury was observed via histological examination. Oxidative stress and inflammatory response markers, and their signaling pathways were detected. Results: The study found that PKC θ knockout decreased serum AST and ALT levels when compared to the WT mice. Furthermore, heme treatment significantly reduced the ALT and AST levels of the PKC θ deletion mice compared with the untreated PKC θ deletion mice. PKC θ deletion markedly elevated superoxide dismutase activity in the liver tissue, reduced malondialdehyde content in the tissue, and the serum TNF-α and IL-6 levels compared with the WT mice. Heme treatment was observed to elevate the activity of SOD and reduced MDA content and serum of TNF-α and IL 6 in the PKC θ deletion animals. Meanwhile, heme treatment increased HO-1 and Nrf 2 protein expression, and reduced the levels of TLR4, phosphorylated NF-κB, and IKB-α. Conclusion: These findings suggested that PKC θ deletion ameliorates HIR, and heme treatment further improves HIR, which is related to regulation of PKC θ deletion on Nrf 2/HO-1 and TLR4/NF-κB/IKB α pathway.
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Diabetic foot ulcers (DFUs) represent a severe complication of diabetes mellitus. Ramulus Mori (Sangzhi) alkaloids (SZ-A), an approved oral medication for type 2 diabetes, have not been explored for their potential to enhance the processes involved in diabetic wound healing. This study aims to investigate SZ-A's role in diabetic wound healing mechanisms. The in vivo experimentation involves dividing the subjects into NC and SZ-A groups, with SZ-A dosed at 200 and 400 mg/kg, to assess the therapeutic efficacy of SZ-A. The results of the animal studies show that SZ-A intervention accelerates the processes of diabetic angiogenesis and wound healing in a manner dependent on its concentration. Additionally, a pathological model using advanced glycation end products (AGEs) in HUVECs demonstrates SZ-A's cytoprotective effect. In vitro, SZ-A intervention significantly increases cell proliferation, migration and tube formation, protecting HUVECs from oxidative stress injury induced by AGEs. Mechanistically, SZ-A exerts a protective effect on HUVECs from oxidative stress damage through the activation of the NRF2/HO-1/eNOS signaling pathway. The findings suggest that SZ-A exhibits considerable potential as a promising candidate for treating DFUs, which will aid in more effectively integrating plant-based therapies into clinical settings.
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Ganweikang tablet (GWK) is a traditional Chinese prescription and has been clinically used in treating liver diseases for decades. Although GWK has been shown to exert potential therapeutic effect for hepatotoxicity protection, the underlying biological mechanisms are still not well clarified. In the present study, the compositional analysis of GWK was performed by HPLC analysis, and the hepato-protective effects of GWK were assessed in H2O2-stimulated acute oxidative injured HL-7702 hepatocytes in vitro. As a result, 7 components in GWK were quantified to be 0.06 ± 0.01% (calycosin), 0.46 ± 0.02% (calycosin-7-glucoside), 0.13 ± 0.01% (liquiritin), 0.17 ± 0.02% (glycyrrhizic acid), 0.45 ± 0.02% (forsythoside A), 0.07 ± 0.01% (5-O-methylvisammioside) and 0.45 ± 0.02% (forsythin), respectively. Furthermore, GWK (100, 200 and 400 µg/mL, 24 h) dose-dependently alleviated HL-7702 hepatocytes from H2O2 (200 µM, 2 h)-induced cell apoptosis by decreasing the intracellular reactive oxygen species (ROS) generation and malondialdehyde (MDA) level, as well as the cellular aminotransferases (ALT and AST) activities. GWK increased the expressions of HO-1, NQO1 and Nrf2, while suppressing the expression of KEAP1 in H2O2-stimulated HL-7702 cells. A specific Nrf2 inhibitor, ML385, was further employed to investigate the regulation of Nrf2 in HL-7702 cells stimulated by H2O2. In addition, the activation of MAPKs (JUN, ERK and p38) was simultaneously detected in H2O2-stimulated HL-7702 cells. In conclusion, GWK exerted potential therapeutic effect to protect hepatocytes from acute oxidative injury through activating the Nrf2/HO-1 and MAPKs pathways.
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Medicamentos Herbarios Chinos , Hemo-Oxigenasa 1 , Hepatocitos , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Factor 2 Relacionado con NF-E2/metabolismo , Hepatocitos/efectos de los fármacos , Humanos , Medicamentos Herbarios Chinos/farmacología , Estrés Oxidativo/efectos de los fármacos , Hemo-Oxigenasa 1/metabolismo , Línea Celular , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sustancias Protectoras/farmacología , Peróxido de Hidrógeno/toxicidadRESUMEN
An effective method was developed for preparing galloylated procyanidins (GPCs) using galloyl-attached nucleophilic degradation. Under degradation conditions optimized through Box-Behnken design and single-factor experiments, two dimeric and three tetrameric GPCs were produced, with the yield of procyanidin B2-3'-O-gallate (B2-3'-G) reaching up to 232 mg/g (PPCs). The structure of B2-3'-G was identified by UV, FTIR, NMR, CD, MS, and phloroglucinolysis. Furthermore, the protective effect of B2-3'-G against alcohol-induced liver injury (ALI) was investigated. Compared with the parent compounds, B2-3'-G exhibited a stronger capacity for inhibiting ALI, attributed to its polymerization degree and galloyl group. Subsequent experiments revealed that the pretreatment of BRL-3A cells with B2-3'-G prior to ethanol improved ALI through activation of the Nrf2-HO-1/NQO1 pathway and initiation of enzymatic antioxidant systems. These findings suggest that GPC B2-3'-G is a potential hepatoprotective agent, which provides a new perspective for functional development of GPCs.
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Biflavonoides , Catequina , Proantocianidinas , Sustancias Protectoras , Vitis , Proantocianidinas/química , Proantocianidinas/farmacología , Biflavonoides/química , Biflavonoides/farmacología , Catequina/química , Catequina/farmacología , Catequina/análogos & derivados , Sustancias Protectoras/farmacología , Sustancias Protectoras/química , Animales , Vitis/química , Ratas , Semillas/química , Humanos , Extracto de Semillas de Uva/química , Extracto de Semillas de Uva/farmacología , Hígado/efectos de los fármacos , Hígado/metabolismo , Línea Celular , Hemo-Oxigenasa 1/metabolismo , Hemo-Oxigenasa 1/genética , Polímeros/química , Polímeros/farmacologíaRESUMEN
BACKGROUND: Depression is a serious and complex mental disease that has attracted worldwide attention because of its high incidence rate, high disability rate and high mortality. Excitotoxicity is one of the most important mechanisms involved in the pathophysiological process of depression. In our previous studies, n-butanol extract from maize roots was found to have good neuroprotective effects due to its antioxidative activity. However, the antidepressive effective constituents, efficacy in vivo and mechanism of action of maize root extracts have not been determined. PURPOSE: This study aimed to determine the main active neuroprotective compound in maize root extract and investigate its antidepressant effects and possible underlying mechanism in vitro and in vivo. METHODS: Sixteen extracts were isolated and purified from maize roots. The active components of the most active extracts of maize roots (hereafter referred to as EM 2) were identified using UF-HPLC-QTOF/MS. In vitro cell models of NMDA-induced excitotoxicity in SH-SY5Y cells were used to analyze the anti-excitatory activity of the extracts. The MTT assay and Annexin V-FITC/PI Apoptosis Detection were used to evaluate cell viability. Several network pharmacological strategies have been employed to investigate the potential mechanism of action of EM 2. The effects of EM 2 on depressive-like behaviors were evaluated in CUMS mice. Changes in the levels of related proteins were detected via western blotting. RESULTS: Among the 16 extracts extracted by n-butanol, EM 2 was determined to be the most active extract against NMDA-induced excitotoxicity by n-butanol extraction. Meanwhile, seventeen compounds were further identified as the main active components of EM 2. Mechanistically, EM 2 inhibited NMDA-induced excitatory injury in SH-SY5Y cells and alleviated the depressive-like behaviors of CUMS mice by suppressing NR2B and subsequently mediating the downstream CREB/TRKB/BDNF, PI3K/Akt and MAPK pathways, as well as the Nrf2/HO-1 antioxidant signaling pathway. CONCLUSION: The study indicated that EM 2 could potentially be developed as a potential therapeutic candidate to cure depression in NMDA-induced excitatory damage.
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Antidepresivos , Apoptosis , Depresión , Fármacos Neuroprotectores , Extractos Vegetales , Raíces de Plantas , Zea mays , Animales , Antidepresivos/farmacología , Zea mays/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Raíces de Plantas/química , Humanos , Ratones , Depresión/tratamiento farmacológico , Fármacos Neuroprotectores/farmacología , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Masculino , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Supervivencia Celular/efectos de los fármacos , Receptores de N-Metil-D-Aspartato/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Acute kidney injury (AKI) is a syndrome characterized by the rapid loss of the renal function and has high morbidity and mortality worldwide, yet there is no satisfactory means of prevention and treatment at present. Dioscin, a natural steroidal saponin, has been found to have antioxidant, anti-inflammatory and anti-apoptotic effects. In this experiment, we pretreated cisplatin-induced AKI rats with dioscin and found that dioscin significantly enhanced renal function and reduced renal pathological injury in AKI rats. We also found that dioscin improved renal antioxidant capacity by suppressing the accumulation of oxides such as ROS, MDA and H2O2, and increasing the levels of antioxidant enzymes SOD and CAT. In addition, dioscin down-regulated the expression of inflammation-related proteins (IL-1ß, TNF-α, NF-κB) and necroptosis-critical proteins RIP1/RIP3, whereas up-regulated Caspase-8 protein levels in the kidney of AKI rats. Mechanistically, dioscin promoted the nuclear transcription of Nrf2 and activated Nrf2/HO-1 signaling axis to play a positive role in the kidney of AKI rats, while the reno-protective effect of dioscin was significantly attenuated after inhibiting Nrf2. In conclusion, our data indicate that dioscin decreases cisplatin-induced renal oxidative stress and thwarts necroptosis induced inflammation via regulating the Nrf2/HO-1pathway. Our study provides more data and theoretical support for the study of natural drugs to improve AKI.
Asunto(s)
Lesión Renal Aguda , Antiinflamatorios , Cisplatino , Diosgenina , Riñón , Necroptosis , Estrés Oxidativo , Ratas Sprague-Dawley , Animales , Diosgenina/análogos & derivados , Diosgenina/farmacología , Diosgenina/uso terapéutico , Estrés Oxidativo/efectos de los fármacos , Masculino , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/patología , Lesión Renal Aguda/metabolismo , Cisplatino/efectos adversos , Necroptosis/efectos de los fármacos , Riñón/efectos de los fármacos , Riñón/patología , Riñón/metabolismo , Ratas , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Factor 2 Relacionado con NF-E2/metabolismo , Transducción de Señal/efectos de los fármacos , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Inflamación/tratamiento farmacológico , Humanos , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: Ulcerative colitis (UC), a chronic idiopathic inflammatory bowel disease (IBD), presents with limited current drug treatment options. Consequently, the search for safe and effective drug for UC prevention and treatment is imperative. Our prior studies have demonstrated that the phenolic compound p-Hydroxybenzaldehyde (HD) from Nostoc commune, effectively mitigates intestinal inflammation. However, the mechanisms underlying HD's anti-inflammatory effects remain unclear. PURPOSE: This study delved into the pharmacodynamics of HD and its underlying anti-inflammation mechanisms. METHODS: For in vivo experiments, dextran sodium sulfate (DSS)-induced colitis mouse model was established. In vitro inflammation model was established using lipopolysaccharide (LPS)-induced RAW264.7 and bone marrow-derived macrophages (BMDMs). The protective effect of HD against colitis was determined by monitoring clinical symptoms and histological morphology in mice. The levels of inflammatory factors and oxidative stress markers were subsequently analyzed with enzyme-linked immunosorbent assay (ELISA) and biochemical kits. Furthermore, western blotting (WB), immunofluorescence (IF), luciferase reporter gene, drug affinity reaction target stability (DARTS) assay, molecular docking, and molecular dynamics (MD) simulation were used to determine the potential target and molecular mechanism of HD. RESULTS: Our findings indicate that HD significantly alleviated the clinical symptoms and histological morphology of colitis in mice, and curtailed the production of pro-inflammatory cytokines, including TNF-α, IL-6, IFN-γ, COX-2, and iNOS. Furthermore, HD stimulated the production of SOD, CAT, and GSH-px, enhanced total antioxidant capacity (T-AOC), and reduced MDA levels. Mechanically, HD augmented the expression of Nrf2, HO-1, and NQO-1, while concurrently downregulating the phosphorylation of p65, IκBα, c-Jun, and c-Fos. ML385 and siNrf2 largely attenuated the protective effect of HD in enteritis mice and RAW 264.7 cells, as well as the promotion of HO-1 expression levels. ZnPP-mediated HO-1 knockdown reversed HD-induced inhibition of colonic inflammation. Luciferase reporter assay and IF assay confirmed the transcriptional activation of Nrf2 by HD. DARTS analysis, molecular docking, and MD results showed high binding strength, interaction efficiency and remarkable stability between Nrf2 and HD. CONCLUSION: These outcomes extend our previous research results that HD can combat oxidative stress through the Nrf2/HO-1/NQO-1/NF-κB/AP-1 pathways, effectively alleviating colitis, and propose new targets for HD to protect against intestinal barrier damage.