Microfluidized hemp protein isolate: an effective stabilizer for high-internal-phase emulsions with improved oxidative stability.

BACKGROUND: Hemp protein isolates (HPIs), which provide a well-balanced profile of essential amino acids comparable to other high-quality proteins, have recently garnered significant attention. However, the underutilized functional attributes of HPIs have constrained their potential commercial applications within the food and agriculture field. This study advocates the utilization of dynamic-high-pressure-microfluidization (DHPM) for the production of stable high-internal-phase emulsions (HIPEs), offering an efficient approach to fully exploit the potential of HPI resources. RESULTS: The findings underscore the effectiveness of DHPM in producing HPI as a stabilizing agent for HIPEs with augmented antioxidant activity. Microfluidized HPI exhibited consistent adsorption and anchoring at the oil-water interface, resulting in the formation of a dense and compact layer. Concurrently, the compression of droplets within HIPEs gave rise to a polyhedral framework, conferring viscoelastic properties and a quasi-solid behavior to the emulsion. Remarkably, HIPEs stabilized by microfluidized HPI demonstrated superior oxidative and storage stability, attributable to the establishment of an antioxidative barrier by microfluidized HPI particles. CONCLUSION: This study presents an appealing approach for transforming liquid oils into solid-like fats using HPI particles, all without the need for surfactants. HIPEs stabilized by microfluidized HPI particles hold promise as emerging food ingredients for the development of emulsion-based formulations with enhanced oxidative stability, thereby finding application in the food and agricultural industries. © 2023 Society of Chemical Industry.

Necroptosis-related subtypes are associated with bronchiectasis in pulmonary non-tuberculous mycobacteria-infected patients: a perspective based on transcriptomic analysis.

The aim of this study was to explore the potential mechanisms responsible for the different manifestations of bronchiectasis in patients with pulmonary non-tuberculous mycobacteria (pNTM) infection. We found that the necroptosis level increased significantly after NTM infection. Further, the 31 pNTM-infected patients were classified into two subtypes based on necroptosis-related genes (NRGs) by unsupervised cluster analysis. After that, we compared the differences in clinical parameters, immune cell infiltration, and gene expression between the two subtypes. We observed that the high-necroptosis subtype possessed higher CT scores for bronchiectasis extent (P = 0.008) and severity (P = 0.023). And, more neutrophil infiltration in the high-necroptosis subtype was demonstrated both by the CIBERSORT algorithm and by blood neutrophil count (P = 0.001). Next, 688 differentially expressed genes (DEGs) between two subtypes were identified. To explore the portion in DEGs that might contribute to bronchiectasis, we intersected the DEGs with two gene modules. These two gene modules were identified as the most associated with CT scores for bronchiectasis extent and severity by weighted gene co-expression network analysis (WGCNA). Ninety-three intersection genes were obtained. Finally, 7 hub genes including ACSL1, ANXA3, DYSF, HK3, SLC11A1, STX11, and TLR4 were further screened out by machine learning algorithms and protein-protein interaction network analysis. These results suggested that the differential levels of necroptosis in pNTM patients might lead to differential extent and severity of bronchiectasis on radiographic imaging. This process might be associated with neutrophil infiltration and the involvement of seven hub genes.

Influence of different processing times on the quality of Polygoni Multiflora Radix by metabolomics based on ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry.

A metabolomics method based on ultra high performance liquid chromatography with quadrupole time-of-flight mass spectrometry was developed to evaluate the influence of processing times on the quality of raw and processed Polygoni Multiflora Radix. Principal component analysis and partial least-squares discriminant analysis was used to screen the potential maker metabolites that were contributed to the quality changes. Then these marker metabolites were selected as variables in Fisher's discriminant analysis to establish the models that were used to distinguish the raw and processed Polygoni Multiflora Radix in the markets. Additionally, 36 compounds were identified. Twelve raw Polygoni Multiflora Radix samples and 23 processed Polygoni Multiflora Radix samples were distinguished. The results showed that the 12 raw Polygoni Multiflora Radix samples belonged to the group of processing time of 0 h, and two processed Polygoni Multiflora Radix samples were part of the group of processing times of 4 h, 12 samples belonged to group of processing times of 8 to 16 h, and nine samples were the group of processing times of 24 to 48 h. The results demonstrated that the method could provide scientific support for the processing standardization of Polygoni Multiflora Radix.

Effect of diosmetin on airway remodeling in a murine model of chronic asthma.

Bronchial asthma, one of the most common allergic diseases, is characterized by airway hyperresponsiveness (AHR), inflammation, and remodeling. The anti-oxidant flavone aglycone diosmetin ameliorates the inflammation in pancreatitis, but little is known about its impact on asthma. In this study, the effects of diosmetin on chronic asthma were investigated with an emphasis on the modulation of airway remodeling in BALB/c mice challenged with ovalbumin (OVA). It was found that diosmetin significantly relieved inflammatory cell infiltration, goblet cell hyperplasia, and collagen deposition in the lungs of asthmatic mice and notably reduced AHR in these animals. The OVA-induced increases in total cell and eosinophil counts in bronchoalveolar lavage fluid were reversed, and the level of OVA-specific immunoglobulin E in serum was attenuated by diosmetin administration, implying an anti-Th2 activity of diosmetin. Furthermore, diosmetin remarkably suppressed the expression of smooth muscle actin alpha chain, indicating a potent anti-proliferative effect of diosmetin on airway smooth muscle cells (ASMCs). Matrix metallopeptidase-9, transforming growth factor-ß1, and vascular endothelial growth factor levels were also alleviated by diosmetin, suggesting that the remission of airway remodeling might be attributed to the decline of these proteins. Taken together, our findings provided a novel profile of diosmetin with anti-remodeling therapeutic benefits, highlighting a new potential of diosmetin in remitting the ASMC proliferation in chronic asthma.

Ultra high performance liquid chromatography with photodiode array detector and quadrupole time-of-flight tandem mass spectrometry coupled with discriminant analysis to evaluate Angelicae pubescentis radix from different regions.

A rapid and effective method was developed for the qualitative and quantitative analysis of the major chemical constituents in Angelicae pubescentis radix by ultra high performance liquid chromatography with photodiode array detection and quadrupole time-of-flight tandem mass spectrometry. The chromatographic separation was achieved on an ACQUITY UHPLC BEH C18 column (2.1 × 100 mm, 1.7 µm). Nine phenolic acids, 30 coumarins, bisabolangelone, and adenosine were identified by quadrupole time-of-flight tandem mass spectrometry. All calibration curves exhibited good linearity (r > 0.9996) within the linear ranges. The relative standard deviation calculated for intraday and interday precision, stability, and accuracy were <5%. The mean recovery ranged from 95.8 to 106%. The overall limits of detection and quantification were 0.025-0.160 and 0.100-0.560 µg/mL, respectively. Discriminant analysis was investigated as a method for evaluating the quality of the samples with 100% correction in their classification. The results demonstrated that the developed method could successfully be used to differentiate samples from different regions and could be a helpful tool for detection and confirmation of the quality of traditional Chinese medicines.

Quality-of-Life Bronchiectasis Respiratory Symptom Scale Predicts the Risk of Exacerbations in Adults with Bronchiectasis: A Prospective Observational Study.

Rationale: The relationship between symptoms, measured using a validated disease-specific questionnaire, and longitudinal exacerbation risk has not been demonstrated in bronchiectasis. Objectives: The aim of this study is to investigate whether baseline symptoms, assessed using the Quality-of-Life Bronchiectasis Respiratory Symptom Scale (QoL-B-RSS) and its individual component scores, could predict future exacerbation risk in patients with bronchiectasis. Methods: The study included 436 adults with bronchiectasis from three tertiary hospitals. Symptoms were measured using the QoL-B-RSS, with scores ranging from 0 to 100, where lower scores indicated more severe symptoms. We examined whether symptoms as continuous measures were associated with the risk of exacerbation over 12 months. The analysis was also repeated for individual components of the QoL-B-RSS score. Results: The baseline QoL-B-RSS score was associated with an increased risk of exacerbations (rate ratio, 1.25 for each 10-point decrease; 95% confidence interval [CI], 1.15-1.35; P < 0.001), hospitalizations (rate ratio, 1.24; 95% CI, 1.05-1.43; P = 0.02), and reduced time to the first exacerbation (hazard ratio, 1.12; 95% CI, 1.03-1.21; P = 0.01) over 12 months, even after adjusting for relevant confounders, including exacerbation history. The QoL-B-RSS score was comparable to exacerbation history in its association with future frequent exacerbations (defined as three or more exacerbations per year) and hospitalization (area under the curve, 0.86 vs. 0.84; P = 0.46; and area under the curve, 0.81 vs. 0.83; P = 0.41, respectively). Moreover, patients with more severe symptoms in the majority of individual components of the QoL-B-RSS were more likely to experience exacerbations. Conclusions: Symptoms can serve as useful indicators for identifying patients at increased risk of exacerbation in bronchiectasis. Beyond relying solely on exacerbation history, a comprehensive assessment of symptoms could facilitate timely and cost-effective implementation of interventions for exacerbation prevention.

Updated severity and prognosis score of pulmonary alveolar proteinosis: A multi-center cohort study in China.

Background: The high-resolution computed tomography (HRCT) score is an important component of the severity and prognosis score of pulmonary alveolar proteinosis (SPSP). However, the HRCT score in SPSP only considers the extent of opacity, which is insufficient. Methods: We retrospectively evaluated HRCT scores for 231 patients with autoimmune pulmonary alveolar proteinosis (APAP) from three centers of the China Alliance for Rare Diseases. The SPSPII was created based on the overall density and extent, incorporating the SPSP. The severity of APAP patients was assessed using disease severity scores (DSS), SPSP, and SPSPII to determine the strengths and weaknesses of the different assessment methods. We then prospectively applied the SPSPII to patients before treatment, and the curative effect was assessed after 3 months. Results: The HRCT overall density and extent scores in our retrospective analysis were higher than the extent scores in all patients and every original extent score severity group, as well as higher related to arterial partial oxygen pressure (PaO2) than extent scores. The mild patients accounted for 61.9% based on DSS 1-2, 20.3% based on SPSP 1-3, and 20.8% based on SPSPII 1-3. Based on SPSP or SPSPII, the number of severe patients deteriorating was higher in the mild and moderate groups. When applied prospectively, arterial PaO2 differed between any two SPSPII severity groups. The alveolar-arterial gradient in PaO2 (P[A-a]O2), % predicted carbon monoxide diffusing capacity of the lung (DLCO), and HRCT score were higher in the severe group than in the mild and moderate groups. After diagnosis, mild patients received symptomatic treatment, moderate patients received pure whole lung lavage (WLL) or granulocyte-macrophage colony-stimulating factor (GM-CSF) therapy, and severe patients received WLL and GM-CSF therapy. Importantly, the SPSPII in mild and severe groups were lower than baseline after 3 months. Conclusion: The HRCT density and extent scores of patients with APAP were better than the extent score. The SPSPII score system based on smoking status, symptoms, PaO2, predicted DLCO, and overall HRCT score was better than DSS and SPSP for assessing the severity and efficacy and predicting the prognosis. Trial registration: ClinicalTrial.gov, identifier: NCT04516577.

[Stenting treatment of venous sinus stenosis for intractable pulsatile tinnitus].

OBJECTIVE: To evaluate the application, effectiveness and safety of stenting in venous sinus stenosis for intractable pulsatile tinnitus via endovascular treatment. METHODS: From January 2010 to July 2011, 12 cases with intractable pulsatile tinnitus originating from cerebral venous sinus stenosis underwent stenting treatment. All of them were diagnosed by digital subtraction angiography (DSA). There was ipsilateral stenosis in junction segment of sigmoid and transverse sinuses. The diverticulum of sigmoid sinus was found in 6 cases. Eleven patients underwent stenting placement and angioplasty for venous sinus stenosis. RESULTS: All pulsatile tinnitus symptoms disappeared immediately after stenting. No related complication was found during stenting and over a follow-up period of 3 - 22 months. There was no recurrence of pulsatile tinnitus. CONCLUSIONS: Stent placement is a safe and effective procedure for pulsatile tinnitus with cerebral venous sinus stenosis.

[Evaluation of carotid angiography and stenting for patients with contralateral carotid occlusion].

OBJECTIVE: To discuss the efficiency and safety of carotid angioplasty stenting (CAS) in patients with contralateral carotid artery occlusion. METHODS: From January 2001 to January 2010, 56 carotid artery stenosis patients with contralateral carotid artery occlusion were performed CAS and the feature and results of these cases were analyzed retrospectively. All the cases were confirmed to be carotid artery stenosis with contralateral carotid artery occlusion by digital subtraction angiography (DSA). The diameter stenosis rate was 72% ± 15%. CAS were performed with distal protection device in 56 cases. RESULTS: The technique success rate of CAS were 100% in all the 56 patients with contralateral carotid artery occlusion and post-procedure stenosis rate descended to 13% ± 8%, and the symptoms of cerebral ischemia were all improved. Only 1 case occurred remote hemorrhage in the position of previous cerebral infarction in the side of CAS after the procedure, and recovered with light neurological deficit after the craniotomy to remove the hematoma. No ischemic complications or death occurred. During the following up of 6 months to 3 years, no cerebral ischemic symptoms reoccurred. The rechecking results of color Doppler of 47 cases and DSA of 2 cases showed no restenosis in-stent. CONCLUSIONS: CAS is safe and effective for the patients with contralateral carotid artery occlusion. Critical election of the case, operation of skilled doctors and scrupulous post procedure general management can decrease the rate of complication.

[Clinical study on endovascular treatment for symptomatic atherosclerotic stenosis of basilar artery].

OBJECTIVE: To study the feasibility, safety and validity of percutaneous angioplasty and stenting (PTAS) for symptomatic atherosclerotic stenosis of basilar artery. METHODS: The results of treatment and follow-up of 40 cases with symptomatic atherosclerotic stenosis of basilar artery performed PTAS from August 2003 to December 2009 were studied retrospectively, who had either recurrent transient ischemic attacks (TIAs) or obvious ischemic symptoms and resistant to medical therapy. RESULTS: PTAS were successfully performed in all the 40 cases and the post-operative average residual stenosis descended to 14% ± 11% from pre-operative 82% ± 14%. After operation the patients were administrated with antiplatelet drugs. After procedure the clinic symptoms and signs of ischemia were improved obviously in 38 cases and deteriorated in 2 cases whose CT scanning showed that the range of infarction in brain stem enlarged. The symptoms improved after treatment but 2 patients had neurological deficit. No hemorrhagic complications occurred in the group. During the follow-up for 2 months to 7 years, transcranial doppler ultrasonography in 26 cases demonstrated the blood flow was faster than normal in 2 cases, and digital subtraction angiography (DSA) in 6 cases showed restenosis in-stent in 1 case. The second stent was implanted because of the symptomatic restenosis. In another case the follow-up DSA showed occlusion of basilar artery in-stent but there was no ischemia of post circulation because the generation of anastomoses. CONCLUSIONS: PTAS is a feasible, safe and effective therapeutic method for the patients with symptomatic atherosclerotic stenosis of basilar artery. Further study in large number of patients is needed for long-term outcome.

[Studies on photoinduced electron and proton transfer reactions of nucleic acid and aromatic ketone].

The transient absorption spectra of two aromatic ketones (benzophenone (BP), xanthone (XT)) and four nucleic acids (guanosine 5'-monophosphate (GMP), adenosine 5'-monophosphate (AMP), cytidine 5'-monophosphate (CMP), thymidine 5'-monophosphate (TMP)) were obtained in 1 : 1 CH3CN/H2O solution by using time-resolved laser flash photolysis at 355 nm. From the changes of the transient absorption spectra the authors can conclude that photoinduced proton transfer following electron transfer from GMP and AMP to excited BP and XT occurs, which is in accordance with free energy change of the reactions. For CMP and TMP, electron transfer and proton transfer do not appear because no ketyl and anion radical are generated. In addition, the rate constants for electron transfer from GMP, AMP, CMP, and TMP to the excited BP and XT were determined. As can be seen, there is a good correlation between kq and the free energy changes (deltaG) of the electron transfer reaction.

[Cause and treatment for intracranial hemorrhage during the perioperative period of carotid artery stenting].

OBJECTIVES: To discuss the possible cause of intracranial hemorrhage and treatment after carotid artery stenting (CAS) in patients with carotid artery stenosis. METHODS: From January 2003 to August 2009, 403 patients with carotid artery stenosis that were performed CAS, intracranial hemorrhage occurred in 5 cases after the procedure. We analyzed the feature of these cases and perioperative management retrospectively to summarize the possible cause of intracranial hemorrhage and preventive measure. RESULTS: Cerebral hemorrhage were found 30 min after CAS in 2 cases, 5 days in 2 cases and 3 days in 1 case. One patient was treated conservatively whose hemorrhage was about 2 ml, one was performed draining of ventricle and the other three cases were all performed craniotomy to remove the hematoma and to depress. The position of hemorrhage were all in the side of carotid artery stenosis, and in 2 cases of them the hemorrhage were at the region of previous cerebral infarction. One patient was cured conservatively, the one who was performed draining of ventricle died. Among the other three cases performed craniotomy, one recovered with light neurological deficit and two died of multiple organ failure. CONCLUSION: Intracranial hemorrhage is the most serious complication of CAS of carotid artery, and general measure should be taken to prevent it from occurring.

[Endovascular interventional treatment for symptomatic stenosis of middle cerebral artery].

OBJECTIVE: To study the feasibility, security and validity of percutaneous angioplasty (PTA) or percutaneous angioplasty and stenting (PTAS) for symptomatic stenosis of middle cerebral artery. METHODS: The results of treatment and follow-up of 39 cases with symptomatic stenosis of middle cerebral artery who had either recurrent transient ischemic attacks (TIAs) or resistant to medical therapy and were performed PTA or PTAS were studied retrospectively. RESULTS: Among the 39 cases with stenosis of middle cerebral artery (23 in left, 13 in right, 3 in bilateral side and 5 cases combining with stenosis of carotid artery) PTA were successfully performed in 9 cases and PTAS in 30 (whose post-operative residual stenosis were less than 10%). After operation the patients were administrated with antiplatelet drugs. The clinic symptom and sign of ischemia were improved obviously after operation. During the procedure the contrast could be seen outside the vessel in 2 cases, the patients had no obvious symptom of hemorrhage and got well rapidly. But in another case her consciousness changed 1 h after PTAS and the limbs could not move in right side. Emergency CT scan showed cerebral hemorrhage in left basic node area. The patient suffered language barrier and incomplete hemiplegy in right side. No complication was occurred in the others. During 5 to 60 months follow-up, the symptom of weakness in right arm reoccurred but lighter than before in only one case. TCD rechecked in 26 cases and demonstrated the blood beam speed was faster than normal in two case. DSA rechecked in 14 cases showed restenosis in-stent in the 2 cases and they were treated by medicine. CONCLUSIONS: PTA and PTAS is a feasible, safe and effective therapeutic method for the patients with symptomatic stenosis of middle cerebral artery. Further study in large number of patients is needed for long-term outcome.

Aquaporin-4 knockout mice exhibit increased hypnotic susceptibility to ketamine.

PURPOSE: This study examines anesthetic/hypnotic effects of ketamine in AQP4 knockout (KO) and wild-type (WT) mice with the particular focus on neurotransmission. MATERIALS AND METHODS: Ketamine (100 mg/kg) was intraperitoneally injected in 16 WT and 16 KO mice. The hypnotic potencies were evaluated by the loss of the righting reflex (LORR). The amino acids neurotransmitter levels in prefrontal cortex were measured by microdialysis. RESULTS: This study demonstrated that AQP4 knockout significantly shortened the latency compared with WT mice (98.0 ± 4.2 vs. 138.1 ± 15.0 s, p < .05) and prolonged duration of LORR (884.7 ± 58.6 vs. 562.0 ± 51.7 s, p < .05) compared with WT mice in LORR induced by ketamine. Microdialysis showed that lack of AQP4 markedly decreased glutamate level within 20 min (p < .05) and increased γ-aminobutyric acid (GABA) level within 30-40 min (p < .05) after use of ketamine. Moreover, the levels of taurine were remarkably higher in KO mice than in WT mice, but no obvious differences in aspartate were observed between two genotypes. CONCLUSION: AQP4 deficiency led to more susceptibility of mice to ketamine, which is probably due to the modulation of specific neurotransmitters, hinting an essential maintenance of synaptic activity mediated by AQP4 in the action of ketamine.

The role of microRNA-93 regulating angiopoietin2 in the formation of malignant pleural effusion.

The biological roles of miRNAs in the development of malignant pleural effusion (MPE) are unclear. In this study, the miRNA microarray analysis was performed in two different prognosis groups of lung adenocarcinoma patients. Expression profiles of miRNAs in MPEs were identified. With the help of quantification PCR, we confirmed the expression differences of miRNAs and further analyzed their biological functions and relative target genes in vitro. The target gene of miR-93 was estimated by online database, and also, the protein was tested. The target gene and the binding sites of specific miRNA were estimated by online database. The combining capacity of binding sites was verified by luciferase reporter gene assay, and the target gene protein was tested by western blot. We detected 107 miRNAs with expression differences (n = 10) and confirmed significant expression differences in miR-93 and miR-146a in two groups of patients (n = 84). By manipulating miR-93 expression of human lymphatic endothelial cells (HLEC) and human umbilical vein endothelial cells (HUVEC), we discovered that high expression of miR-93 inhibited migration, proliferation, and angiogenesis. And also, miR-93 increased not only apoptosis, but also G1 phase cell block. By using luciferase reporter gene assay and western blot, we confirmed that angiopoietin2 (Ang2) was the target of miR-93. The data showed that miR-93 has an inhibiting effect on pleural effusion. By targeting Ang2, miR-93 regulates angiogenesis and lymphangiogenesis and plays a role in pathogenetic mechanism of MPE. MiR-93/Ang2 may shed light on potential new targets in cancer treatment.

Application of parallel stent placement in the treatment of unruptured vertebrobasilar fusiform aneurysms.

OBJECTIVE Large vertebrobasilar fusiform aneurysms (VFAs) represent a small subset of intracranial aneurysms and are often among the most difficult to treat. Current surgical and endovascular techniques fail to achieve a complete or acceptable result because of complications, including late-onset basilar artery thrombosis and perforator infarction. The parallel-stent placement technique was established in the authors' department, and this study reports the application of this technique in the treatment of unruptured VFAs. METHODS Eight patients with 8 unruptured VFAs who underwent parallel stent placement between April 2011 and August 2012 were included. The diameters of the VFAs ranged from 7.9 to 14.0 mm, and the lengths from 27.5 to 54.4 mm. Of the 8 patients with unruptured VFAs, 3 received double or triple parallel stents and 5 patients received a series-connected stent with another 1 or 2 stents deployed parallel to them. Outcomes for these patients were tabulated, based on the modified Rankin Scale (mRS) score and angiographic results. RESULTS All of the 25 stents were successfully placed without any treatment-related complications. During follow-up, 5 patients had decreased mRS scores, 2 were unchanged, and 1 was increased for subarachnoid hemorrhage. Immediate and follow-up clinical outcome was completely or partially recovered in most patients. Follow-up angiograms revealed 2 aneurysms were reduced in size and 6 were unchanged after stent placement. No in-stent stenosis, occlusion of the posterior inferior cerebellar artery, or perforators jailed by the stent occurred in any of the aneurysms. CONCLUSIONS These results provide encouraging support for the parallel-stent placement technique, which can be envisaged as an alternative strategy against unruptured VFAs. However, testing in more patients is needed.

A Bioactivity-Based Method for Screening, Identification of Lipase Inhibitors, and Clarifying the Effects of Processing Time on Lipase Inhibitory Activity of Polygonum Multiflorum.

Traditional Chinese medicine (TCM) has been used for the treatment of many complex diseases. However, the bioactive components are always undefined. In this study, a bioactivity-based method was developed and validated to screen lipase inhibitors and evaluate the effects of processing on the lipase inhibitory activity of TCM by ultrahigh performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry and fraction collector (UHPLC/Q-TOF-MS-FC). The results showed that both Polygonum multiflorum and processed P. multiflorum extracts had inhibitory effect against lipase with IC50 values of 38.84 µg/mL and 190.6 µg/mL, respectively. Stilbenes, phenolic acid, flavonoids, and anthraquinones were considered to be the potential lipase inhibitors. Eleven potential lipase inhibitors were simultaneously determined by UHPLC. Principal component analysis (PCA) was employed in exploring the effects of processing time on lipase inhibitory activity of P. multiflorum. Compared with conventional methods, a bioactivity-based method could quantitatively analyze lipase inhibitory activity of individual constituent and provide the total lipase inhibitory activity of the samples. The results demonstrated that the activity integrated UHPLC/Q-TOF-MS-FC method was an effective and powerful tool for screening and identifying lipase inhibitors from traditional Chinese medicines.

Morin Attenuates Ovalbumin-Induced Airway Inflammation by Modulating Oxidative Stress-Responsive MAPK Signaling.

Asthma is one of the most common inflammatory diseases characterized by airway hyperresponsiveness, inflammation, and remodeling. Morin, an active ingredient obtained from Moraceae plants, has been demonstrated to have promising anti-inflammatory activities in a range of disorders. However, its impacts on pulmonary diseases, particularly on asthma, have not been clarified. This study was designed to investigate whether morin alleviates airway inflammation in chronic asthma with an emphasis on oxidative stress modulation. In vivo, ovalbumin- (OVA-) sensitized mice were administered with morin or dexamethasone before challenge. Bronchoalveolar lavage fluid (BALF) and lung tissues were obtained to perform cell counts, histological analysis, and enzyme-linked immunosorbent assay. In vitro, human bronchial epithelial cells (BECs) were challenged by tumor necrosis factor alpha (TNF-α). The supernatant was collected for the detection of the proinflammatory proteins, and the cells were collected for reactive oxygen species (ROS)/mitogen-activated protein kinase (MAPK) evaluations. Severe inflammatory responses and remodeling were observed in the airways of the OVA-sensitized mice. Treatment with morin dramatically attenuated the extensive trafficking of inflammatory cells into the BALF and inhibited their infiltration around the respiratory tracts and vessels. Morin administration also significantly suppressed goblet cell hyperplasia and collagen deposition/fibrosis and dose-dependently inhibited the OVA-induced increases in IgE, TNF-α, interleukin- (IL-) 4, IL-13, matrix metalloproteinase-9, and malondialdehyde. In human BECs challenged by TNF-α, the levels of proteins such as eotaxin-1, monocyte chemoattractant protein-1, IL-8 and intercellular adhesion molecule-1, were consistently significantly decreased by morin. Western blotting and the 2',7'-dichlorofluorescein assay revealed that the increases in intracellular ROS and MAPK phosphorylation were abolished by morin, implying that ROS/MAPK signaling contributes to the relief of airway inflammation. Our findings indicate for the first time that morin alleviates airway inflammation in chronic asthma, which probably occurs via the oxidative stress-responsive MAPK pathway, highlighting a novel profile of morin as a potent agent for asthma management.

Diosmetin prevents TGF-ß1-induced epithelial-mesenchymal transition via ROS/MAPK signaling pathways.

AIMS: Epithelial-mesenchymal transition (EMT) plays a critical role in airway repair and remodeling in many respiratory diseases such as asthma and pulmonary fibrosis. The flavone aglycone, diosmetin, possesses anti-remodeling activity in a murine model of chronic asthma, but little is known about its effects on EMT. Herein, we investigated whether diosmetin inhibits transforming growth factor-ß1 (TGF-ß1)-induced EMT with underlying mechanisms in human bronchial epithelial (HBE) cells. MAIN METHODS: HBE cells were incubated with TGF-ß1 (10ng/ml), either alone or in combination with diosmetin for indicated times. We measured reactive oxygen species (ROS) levels using FACScan and immunofluorescent assays. We assessed protein expression of NADPH oxidase 4 (NOX4), superoxide dismutase (SOD), catalase, Akt, Erk, p38, and phosphorylation levels of Akt, Erk and p38 by Western blot analysis. KEY FINDINGS: TGF-ß1 promoted EMT and ROS generation in HBE cells. Diosmetin significantly suppressed TGF-ß1-induced increases in cell migration and altered N-cadherin, E-cadherin, and α-smooth muscle actin expression. In addition, diosmetin prevented TGF-ß1-induced intracellular ROS generation, down-regulated NOX4, and up-regulated SOD and catalase expression. Furthermore, diosmetin remarkably inhibited TGF-ß1-induced phosphorylation of phosphoinositide 3-kinase (PI3K)/Akt and mitogen activated protein kinase (MAPK) pathways in HBE cells. SIGNIFICANCE: Our results demonstrate for the first time that diosmetin alleviates TGF-ß1-induced EMT by inhibiting ROS generation and inactivating PI3K/Akt and MAPK pathways. Our findings revealed a new role for diosmetin in reducing airway remodeling and fibrogenesis.