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Dampness-heat syndrome diarrhea (DHSD) is a common clinical disease with a high prevalence but still has no satisfactory therapeutic medicine, so the search for a safe and effective drug candidate is ongoing. This study aims to explore the efficacy and mechanisms of Lianweng granules (LWG) in the treatment of DHSD and to identify the blood transport components of LWG. We assessed the efficacy of LWG in DHSD by various in vivo metrics such as body weight, disease activity index (DAI), histopathologic examination, intestinal barrier function, levels of inflammatory, apoptotic biomarkers, and oxidative stress. We identified the blood components of LWG using ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UHPLC-MS/MS), and the resolved key components were used to explore the relevant targets. We next predicted the potential mechanisms of LWG in treating DHSD using network pharmacology and molecular docking based on the relevant targets. Finally, the mechanisms were validated in vivo using RT-qPCR, Western blotting, ELISA, and immunofluorescence and evaluated in vitro using Cell Counting Kit-8 (CCK-8), small interfering RNA, cellular enthusiasm transfer assay (CETSA), and drug affinity response target stability (DARTS). Ninety-one pharmacodynamic components of LWG enter the bloodstream and exert possible therapeutic effects. In vivo, LWG treatment improved body weight, reduced colonic injury and DAI scores, lowered inflammation, oxidative stress, and apoptosis markers, and partially restored intestinal barrier function in DHSD mice. Guided by network pharmacology and molecular docking, it is suggested that LWG may exert therapeutic effects by inhibiting IL-6/STAT3/PI3K/AKT signaling. LWG significantly decreased the expression of IL-6, p-STAT3, p-PI3K, p-AKT, and other proteins. These findings were supported by in vitro experiments, where CETSA, DARTS, and siRNA evidenced LWG's targeting of STAT3. LWG targeted STAT3 to inhibit inflammation, oxidative stress, and apoptosis in the colon, thereby restoring the intestinal barrier function to some extent and exerting a therapeutic effect on DHSD.
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In the study of surface-enhanced Raman scattering (SERS) processes, a simple and fast approach is needed to ensure the large-scale preparation of SERS substrates. This article uses anodic aluminum oxide (AAO) as a template to assemble gold nanoparticles (Au NPs) into an ordered array. By changing the pore size of AAO and silanizing the pores, the number and density of Au NPs entering the pores through liquid-liquid two-phase self-assembly (LLSA) can be effectively regulated. Using Rh6G (Rhodamine 6G) and CV (Crystal Violet) molecules as probe molecules, substrate sensitivity was evaluated with an enhancement factor of up to 6.34 × 107. In addition, the uniformity of the substrate is good, with a relative standard deviation (RSD) of 9.94%, and the logarithmic concentration and the Raman signal presented significant linear correlations R2 was 0.997 and 0.985, respectively. The detection limit of the substrate for APM (aspartame) as a solvent is as low as 0.0078 g/L. Finally, the substrate was subjected to high sensitivity testing on two types of beverages containing APM sold, proving the practicality of the substrate. It is expected to achieve simple and rapid detection in food additive trace detection in the future.
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Heat-treated adzuki bean protein hydrolysates exhibit lipid-reducing properties; however, few studies have reported pancreatic lipase (PL) and cholesterol esterase (CE) inhibitory effects and elucidated the underlying mechanisms. In this study, we accomplished the identification of antiobesity peptides through peptide sequencing, virtual screening, and in vitro experiments. Furthermore, the mechanisms were investigated via molecular docking. The findings reveal that the action of pepsin and pancreatin resulted in the transformation of intact adzuki bean protein into smaller peptide fragments. The < 3 kDa fraction exhibited a high proportion of hydrophobic amino acids and displayed superior inhibitory properties for both PL and CE. Five novel antiobesity peptides (LLGGLDSSLLPH, FDTGSSFYNKPAG, IWVGGSGMDM, YLQGFGKNIL, and IFNNDPNNHP) were identified as PL and CE inhibitors. Particularly, IFNNDPNNHP exhibited the most robust biological activity. These peptides exerted their inhibitory action on PL and CE by occupying catalytic or substrate-binding sites through hydrogen bonds, hydrophobic interactions, salt bridges, and π-π stacking.
Subject(s)
Vigna , Vigna/genetics , Vigna/metabolism , Sterol Esterase , Protein Hydrolysates/chemistry , Molecular Docking Simulation , Hot Temperature , Lipase/chemistry , Peptides/chemistryABSTRACT
ETHNOPHARMACOLOGICAL RELEVANCE: Diarrhea is a frequently encountered gastrointestinal complication in clinical practice, and E. coli is one of the main causative agents. Although Qingjie decoction (QJD) has been shown to be highly effective in treating diarrhea by eliminating heat-toxin, the underlying molecular mechanisms and pathways of QJD remain unclear. AIM OF REVIEW: The aim of this research was to explore the effects and fundamental mechanism of QJD on diarrhea induced by E.coli in rats. MATERIALS AND METHODS: Initially, we used UHPLC-MS/MS analysis to identify the chemical composition of QJD. Then, we constructed a visualization network using network pharmacology. Next, we utilized metabolomics to identify differentially expressed metabolites of QJD that are effective in treating diarrhea. RESULTS: The chemical composition of QJD was analyzed using UHPLC-MS/MS, which identified a total of 292 components. Using a network pharmacology approach, 127 bioactive compounds of QJD were screened, targeting 171 potential diarrhea treatment targets. TNF-α, IL-6, IL-1ß, and CAT were identified as important targets through visualizing the PPI network. Enrichment analysis demonstrated significant enrichment in the TNF signaling pathway, IL-17 signaling pathway, and PI3K-Akt signaling pathway. QJD showed beneficial effects, such as increased body weight, decreased fecal water content, and reduced inflammatory cell infiltration in the duodenum and colon, as well as maintaining the structure of the duodenum and colon. Metabolomic analysis revealed 32 differentially expressed metabolites in the control, model and QJD-H groups, including glucose, valine, and cysteine. Functional analysis indicated that differential metabolites were related to energy metabolism, including glucose metabolism, TCA cycle, and amino acid metabolism. CONCLUSION: QJD significantly increased body weight, decreased water content in feces, relieved inflammatory cell infiltration, maintained the structure of duodenum and colon. Combining network analysis and metabolomics, QJD exerted therapeutic effects by inhibiting inflammation and oxidative stress, regulating glucose metabolism, tricarboxylic acid metabolism, and amino acid metabolism.
Subject(s)
Drugs, Chinese Herbal , Animals , Rats , Escherichia coli , Phosphatidylinositol 3-Kinases , Tandem Mass Spectrometry , Metabolomics , Energy Metabolism , Diarrhea/chemically induced , Diarrhea/drug therapy , Cysteine , Glucose , Inflammation , Body Weight , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic useABSTRACT
AIM: To determine the 15-year outcomes of laser dacryoplasty (LDP) in patients with lacrimal duct obstruction; and to evaluate LDP combined with intubation using a new silicone tube to treat complicated cases. METHODS: Patients with lacrimal duct obstruction and treated with LDP between April 2000 and April 2005 were investigated retrospectively. Totally 116 eyes with completed 15-year follow-up records were included in this study. For complicated cases (52 eyes of 52 patients), both LDP and intubation using a self-made silicon tube were performed. For patients with uncomplicated obstruction (64 eyes of 61 patients), only LDP was performed. Outcomes were assessed based on results of lacrimal irrigation and degree of symptoms during follow-up. RESULTS: At the follow-up time of 15y, 81 eyes achieved full success (69.8%); 21 eyes got improved (18.1%); and 14 eyes were considered failure (12.1%). The success rate was 71.2% (37/52 eyes) for complicated cases; and 68.8% (44/64 eyes) for uncomplicated cases. No statistically significant difference between two groups was observed (P=0.961). No postoperative complication was observed. CONCLUSION: LDP is a well-tolerated, simple, and effective procedure with satisfactory long-term outcomes in selected patients, which make it a good alternative to conventional dacryocystorhinostomy. In addition, intubation with the self-made mono-canalicular silicone tube facilitates the management of complicated cases with few complications.
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Portulaca oleracea L. (PO) is an edible and medicinal plant used for treating gastrointestinal diseases. However, the effects of PO on ulcerative colitis (UC) and underlying mechanisms remain unclear. This study investigated the effects of PO aqueous extract (POE) and PO juice (PJ) on dextran sulfate sodium (DSS)-induced UC in a mouse model and attempted to unravel their underlying mechanisms. The results revealed that PJ contains more bioactive compounds and has more overlapping targets with UC than POE. Both POE and PJ effectively reduced Disease Activity Index scores and inflammatory cell infiltration in the UC mouse model, but PJ had a better effect than POE. Furthermore, PJ inhibited pyroptosis by decreasing the expression of the NLRP3 inflammasome, while also repairing the dysfunction of the intestinal barrier by upregulating the expression of tight junction proteins. Therefore, based on the study findings, we concluded that PJ can improve DSS-induced UC and may suppress pyroptosis by interfering with the activation of the NLRP3 inflammasome.
Subject(s)
Colitis, Ulcerative , Colitis , Portulaca , Animals , Mice , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Inflammasomes/toxicity , Inflammasomes/metabolism , Colitis/chemically induced , Colitis/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Disease Models, Animal , Mice, Inbred C57BLABSTRACT
BACKGROUND: Artificial intelligence (AI) can improve the health and well-being of older adults and has the potential to assist and improve nursing care. In recent years, research in this area has been increasing. Therefore, it is necessary to understand the status of development and main research hotspots and identify the main contributors and their relationships in the application of AI in geriatric care via bibliometric analysis. OBJECTIVE: Using bibliometric analysis, this study aims to examine the current research hotspots and collaborative networks in the application of AI in geriatric care over the past 23 years. METHODS: The Web of Science Core Collection database was used as a source. All publications from inception to August 2022 were downloaded. The external characteristics of the publications were summarized through HistCite and the Web of Science. Keywords and collaborative networks were analyzed using VOSviewers and Citespace. RESULTS: We obtained a total of 230 publications. The works originated in 499 institutions in 39 countries, were published in 124 journals, and were written by 1216 authors. Publications increased sharply from 2014 to 2022, accounting for 90.87% (209/230) of all publications. The United States and the International Journal of Social Robotics had the highest number of publications on this topic. The 1216 authors were divided into 5 main clusters. Among the 230 publications, 4 clusters were modeled, including Alzheimer disease, aged care, acceptance, and the surveillance and treatment of diseases. Machine learning, deep learning, and rehabilitation had also become recent research hotspots. CONCLUSIONS: Research on the application of AI in geriatric care has developed rapidly. The development of research and cooperation among countries/regions and institutions are limited. In the future, strengthening the cooperation and communication between different countries/regions and institutions may further drive this field's development. This study provides researchers with the information necessary to understand the current state, collaborative networks, and main research hotspots of the field. In addition, our results suggest a series of recommendations for future research.
Subject(s)
Alzheimer Disease , Artificial Intelligence , Humans , Aged , Machine Learning , Bibliometrics , CommunicationABSTRACT
Accuracy of planned corneal stromal thickness (CST) reduction is essential to the safety of laser vision correction. This study was to compare the accuracy of the planned central CST reduction in small incision lenticule extraction (SMILE) and femtosecond laser-assisted in situ keratomileusis (FS-LASIK). A total of 77 patients (43 for SMILE, 34 for FS-LASIK using Custom-Q algorithm) were included in this retrospective study. At postoperative 6-18 months, the central CST reduction was overestimated by 18.49 ± 6.42 µm in the SMILE group (P < 0.001) and underestimated by 2.56 ± 7.79 µm in the FS-LASIK group (P = 0.064). The planned-achieved difference (PAD) of central CST reduction was positively correlated with preoperative manifest refraction spherical equivalent (MRSE) and with planned central CST reduction in both groups. When calculated by manifest refraction (MR) without nomogram adjustment, the central CST reduction was overestimated by 11.14 ± 6.53 µm in the SMILE group and underestimated by 2.83 ± 7.39 µm in the FS-LASIK group. The PAD of central CST reduction without nomogram was significantly narrowed in SMILE and maintained in FS-LASIK, suggesting estimation using MR without nomogram adjustment may be feasible for SMILE and FS-LASIK in clinical practice.
Subject(s)
Keratomileusis, Laser In Situ , Myopia , Surgical Wound , Humans , Retrospective Studies , Visual Acuity , Lasers, Excimer , Myopia/surgery , Prospective Studies , Corneal Stroma/surgery , Surgical Wound/surgeryABSTRACT
Pingwei San (PWS) has been used for more than a thousand years as a traditional Chinese medicine prescription for treating spleen-deficiency diarrhea (SDD). Nevertheless, the exact mechanism by which it exerts its antidiarrheal effects remains unclear. The objective of this investigation was to explore the antidiarrheal efficacy of PWS and its mechanism of action in SDD induced by Rhubarb. To this end, UHPLC-MS/MS was used to identify the chemical composition of PWS, while the body weight, fecal moisture content, and colon pathological alterations were used to evaluate the effects of PWS on the Rhubarb-induced rat model of SDD. Additionally, quantitative polymerase chain reaction (qPCR) and immunohistochemistry were employed to assess the expression of inflammatory factors, aquaporins (AQPs), and tight junction markers in the colon tissues. Furthermore, 16S rRNA was utilized to determine the impact of PWS on the intestinal flora of SDD rats. The findings revealed that PWS increased body weight, reduced fecal water content, and decreased inflammatory cell infiltration in the colon. It also promoted the expression of AQPs and tight junction markers and prevented the loss of colonic cup cells in SDD rats. In addition, PWS significantly increased the abundance of Prevotellaceae, Eubacterium_ruminantium_group, and Tuzzerella, while decreasing the abundance of Ruminococcus and Frisingicoccus in the feces of SDD rats. The LEfSe analysis revealed that Prevotella, Eubacterium_ruminantium_group, and Pantoea were relatively enriched in the PWS group. Overall, the findings of this study indicate that PWS exerted a therapeutic effect on Rhubarb-induced SDD in rats by both protecting the intestinal barrier and modulating the imbalanced intestinal microbiota.
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Inflammatory bowel disease (IBD) represents a highly recurrent gastrointestinal disorder and global public health issue. However, it lacks effective and safe strategies for its control. Although Ginkgo biloba extract (GBE) has been suggested to exhibit preventive and therapeutic activity for the control of IBD, whether its activity is associated with its ability to modulate intestinal microbiota remains to be addressed. To investigate the effect of GBE on controlling IBD, a Citrobacter Rodentium (CR)-induced mouse colitis model was used, and then histopathological examinations, biochemical assays, immunohistochemistry, and immunoblotting were performed to detect histological changes, cytokines, and tight junction (TJ) proteins in the intestine samples. We also studied 16s rRNA to detect changes in intestinal microbiota and used GC-MS to determine the microbiota-related metabolites short chain fatty acids (SCFAs). The results of our studies revealed that pre-treatment with GBE was sufficient for protecting the animals from CR-induced colitis. As a mechanism for GBE activity, GBE treatment was able to modulate the intestinal microbiota and increase the SCFAs capable of decreasing the pro-inflammatory factors and up-regulating the anti-inflammatory factors while elevating the intestinal-barrier-associated proteins to maintain the integrity of the intestines. Accordingly, our results led to a strong suggestion that GBE should be seriously considered in the preventive control of CR-induced colitis and in the development of effective and safe therapeutic strategies for controlling IBD.
Subject(s)
Colitis , Inflammatory Bowel Diseases , Mice , Animals , Citrobacter rodentium , RNA, Ribosomal, 16S , Colitis/chemically induced , Colitis/drug therapy , Colitis/prevention & control , Ginkgo biloba , Mice, Inbred C57BL , Disease Models, AnimalABSTRACT
The aims of this study were to evaluated the effect and underlying mechanism of Gandankang (GDK) aqueous extract in alleviating the acute liver injury induced by carbon tetrachloride (CCl4) in vivo and in vitro. Mice were divided into 5 groups (n = 8) for acute (Groups: control, 0.3 % CCl4, BD (Bifendate), 1.17, 2.34 and 4.68 mg/kg GDK) liver injury study. 10 µL/g CCl4 with corn oil were injected interperitoneally (i.p) expect the control group. HepG2 cells were used in vitro study. The results showed GDK can effectively inhibit liver damage and restore the structure and function of the liver. In mechanism, GDK inhibited CCl4-induced liver fibrosis and blocked the NF-κB pathway to effectively inhibit the hepatic inflammatory response; and inhibited CCl4-induced oxidative stress by upregulating the Keap1/Nrf2 pathway-related proteins and promoting the synthesis of several antioxidants. Additionally, it inhibited ferroptosis in the liver by regulating the expression of ACSl4 and GPX4. GDK reduced lipid peroxide generation in vitro by downregulating the production of reactive oxygen species and Fe2+ aggregation, thereby inhibiting ferroptosis and alleviating CCl4-induced hepatocyte injury. In conclusion, we describe the potential complex mechanism underlying the effect of GDK against acute liver injury.
Subject(s)
Carbon Tetrachloride , Chemical and Drug Induced Liver Injury , Mice , Animals , Carbon Tetrachloride/toxicity , Carbon Tetrachloride/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , NF-E2-Related Factor 2/metabolism , Liver , Antioxidants/metabolism , Oxidative Stress , Signal Transduction , Chemical and Drug Induced Liver Injury/metabolismABSTRACT
Mori fructus aqueous extracts (MFAEs) have been used as a traditional Chinese medicine for thousands of years with the function of strengthening the liver and tonifying the kidney. However, its inner mechanism to alleviative renal injury is unclear. To investigate the attenuation of MFAEs on nephrotoxicity and uncover its potential molecular mechanism, we established a nephrotoxicity model induced by carbon tetrachloride (CCl4). The mice were randomly divided into control group, CCl4 model group (10% CCl4), CCl4 + low and high MFAEs groups (10% CCl4 + 100 mg/kg and 200 mg/kg MFAEs). We found that MFAEs decreased the kidney index of mice, restored the pathological changes of renal structure induced by CCl4, reduced cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (Kim-1) blood urea nitrogen and creatinine contents in serum, promoted the nuclear transportation of Nrf2 (nuclear factor erythroid derived 2 like 2), elevated the expression of HO-1 (heme oxygenase 1), GPX4 (glutathione peroxidase 4), SLC7A11 (solute carrier family 7 member 11), ZO-1 (zonula occludens-1) and Occludin, suppressed the expression of Keap1 (kelch-like ECH-associated protein 1), HMGB1 (High Mobility Group Protein 1), ACSL4 (acyl-CoA synthetase long chain family member 4) and TXNIP (thioredoxin interacting protein), upregulated the flora of Akkermansia, Anaerotruncus, Clostridium_sensu_stricto, Ihubacter, Alcaligenes, Dysosmobacter, and downregulated the flora of Clostridium_XlVa, Helicobacter, Paramuribaculum. Overlapped with Disbiome database, Clostridium_XlVa, Akkermansia and Anaerotruncus may be the potential genera treated with renal injury. It indicated that MFAEs could ameliorate kidney injury caused by CCl4 via Nrf2 signaling.
Subject(s)
Gastrointestinal Microbiome , HMGB1 Protein , Animals , Carbon Tetrachloride/metabolism , Carbon Tetrachloride/toxicity , Coenzyme A/metabolism , Creatinine , Cystatin C/metabolism , HMGB1 Protein/metabolism , Heme Oxygenase-1/metabolism , Kelch-Like ECH-Associated Protein 1/metabolism , Kidney/metabolism , Ligases/metabolism , Lipocalin-2/metabolism , Mice , NF-E2-Related Factor 2/genetics , NF-E2-Related Factor 2/metabolism , Occludin/metabolism , Oxidative Stress , Phospholipid Hydroperoxide Glutathione Peroxidase , Thioredoxins/metabolismABSTRACT
The Tg(Pax6-cre,GFP)2Pgr (α-Cre) mouse is a commonly used Cre line thought to be retinal-specific. Using targeted locus amplification (TLA), we mapped the insertion site of the transgene, and defined primers useful to deduce zygosity. Further analyses revealed four tandem copies of the transgene. The insertion site mapped to clusters of vomeronasal and olfactory receptor genes. Using R26R and Ai14 Cre reporter mice, we confirmed retinal Cre activity, but also detected expression in Gα0+ olfactory neurons. Most α-Cre+ olfactory neurons do not express Pax6, implicating the influence of neighboring regulatory elements. RT-PCR and buried food pellet test did not detect any effects of the transgene on flanking genes in the nasal mucosa and retina. Together, these data precisely map α-Cre, show that it does not affect surrounding loci, but reveal previously unanticipated transgene expression in olfactory neurons. The α-Cre mouse can be a valuable tool in both retinal and olfactory research.
Subject(s)
Neurons , Retina , Animals , Integrases , Mice , Mice, Transgenic , TransgenesABSTRACT
To investigate the relationship between the epicardial adipose tissue density (EATD) and the coronary plaque components as assessed by coronary computed tomographic angiography (CCTA). The study cohort included 240 patients with chest pain or precardiac discomfort (mean age 62.01 ± 7.45 years, 55.83% male). Patients were assigned to the high-risk plaque (HRP) group (n = 133) or non-HRP group (n = 107). All patients underwent CCTA to assess plaque composition, and quantitative analysis of EATD and epicardial adipose tissue volume (EATV). Age, gender, EATV, EATD, diabetes history and family history were all correlated with HRP. There was no linear correlation between EATD and EATV among the subjects (R2 = 0.008, p = 0.177), but there was a curvilinear correlation (R2 = 0.102, p < 0.001). After adjusting other traditional factors, and we observed robust associations of EAT volume and density with HRP (all p < 0.05). For per 1 standard deviation increase in EATD, the risk of HRP was 3.120 times the risk than that of non-HRP. For per 1 standard deviation increase in EATV, the risk of HRP was 1.499 times the risk than that of non-HRP. The receiver operating characteristic curve showed that EATD was more predictive of HRP than EATV (AUC = 0.761, 95% CI 0.701-0.822). Our study found that EATD and EATV are both independent factors affecting the presence of HRPs, and EATD had a high predictive value for the presence of HRP.
Subject(s)
Adipose Tissue , Coronary Angiography , Coronary Artery Disease , Pericardium , Plaque, Atherosclerotic , Adipose Tissue/diagnostic imaging , Aged , Computed Tomography Angiography , Coronary Angiography/methods , Coronary Artery Disease/diagnostic imaging , Female , Humans , Male , Middle Aged , Pericardium/diagnostic imaging , Plaque, Atherosclerotic/diagnostic imaging , Predictive Value of Tests , Risk FactorsABSTRACT
BACKGROUND: Shaoyao decoction (SYD), a traditional Chinese medicine prescription that originated in the Jin-Yuan Dynasty, has shown effects in treating ulcerative colitis. However, the underlying mechanism is unclear. We combined network pharmacology with molecular biology technology to detect the mechanism underlying the effect of SYD on ulcerative colitis. We combined network pharmacology with molecular biology technology to detected the further mechanism in SYD effect on ulcerative colitis. PURPOSE: In this study, we investigated the mechanism by which SYD exerts a protective effect against ulcerative colitis in vivo and in vitro. STUDY DESIGN AND METHODS: We focused on two aspects of the mechanism by which SYD relieves ulcerative colitis, regulation of the MAPK cascade and the NF-κB signaling pathway, through analysis of the "active ingredient-target-disease" network followed by GO enrichment and KEGG pathway analysis according to network pharmacology. Mice with ulcerative colitis underwent 5% dextran sulfate sodium (DSS), and the RAW 264.7 cell model was used to identify important targets. RESULTS: We found that after 5% DSS treatment, the inflammation indexes and the expression of NLRP3-related proteins were increased concomitant with the loss of mucins and occludin. Treatment with SYD (2.25 g/kg, BW) significantly improved the expression of mucins and occludin after DSS at the protein and transcriptional levels. Furthermore, SYD treatment significantly reduced NF-κB P65 and P38 expression, thus exerting a great antinecrotic effect, as revealed by TUNEL staining and Western blotting. The beneficial effects of SYD were almost canceled by NSC 95397 (an inhibitor of mitogen-activated protein kinase phosphatase-1 (MKP1)) after DSS treatment in vivo or LPS treatment in vitro. In addition, treatment with SYD reduced caspase-1 activity and rescued the release of ASC and GSDMD, thus inhibiting the assembly of NLRP3 and maintaining the integrity of the intestinal barrier. We also conducted in vitro experiments in the LPS-induced RAW 264.7 cell model and found that cells incubated with 1 mg/ml SYD for 24 h possessed the highest cell viability. Next, we incubated 1 mg/ml SYD for 24 h after treatment with 1 µg/ml LPS for 6 h. We showed that 1 mg/ml SYD displayed anti-inflammatory and anti-necrotic effects through the NLRP3, NF-κB P65 and P38 pathways, and the effects of SYD were also inhibited by 10 nM NSC 95397. CONCLUSION: These results demonstrate that SYD has protective effects against ulcerative colitis and alleviates pyroptosis by inhibiting the MKP1/NF-κB/NLRP3 pathway.
Subject(s)
Colitis, Ulcerative , Colitis , Animals , Colitis, Ulcerative/chemically induced , Colitis, Ulcerative/drug therapy , Dextran Sulfate , Inflammasomes , Macrophages , Mice , Mice, Inbred C57BL , NF-kappa B , NLR Family, Pyrin Domain-Containing 3 ProteinABSTRACT
Background: Klebsiella pneumonia has emerged as a critical pathogen causing severe clinical problems, such as pneumonia and sepsis. Meanwhile, intensified drug resistance induced by antibiotic therapy necessitates discovering novel and active molecules from Traditional Chinese Medicine (TCM) for treatment. Methods and results: In this study, the isolated Bergenin monohydrate showed an anti-inflammatory effect in Klebsiella-infected mice. We initially investigated the anti-inflammatory effects and cytoprotection against oxidative stress in vitro and in vivo. Interestingly, a specific dose of Bm can effectively ameliorate lung injury and suppress the expression of inflammatory cytokines such as TNF-α, IL-6, IL-1ß and PEG2. Moreover, Bm was also shown to reduced the levels of MPO, MDA and increased SOD and GSH activities. Moreover, we assessed the intracellular signaling molecules including p38, ERK, JNK, IκB, NF-κB-p65 by western blotting and verified through MAPK and NF-κB pathways inhibition experiments. These results reveal that Bm executed its effects via the classical MAPK signaling pathway and NF-κB pathway. Conclusion: Given its underlying anti-inflammatory effect, Bm may be used as a promising therapeutic against Klebsiella-induced infection, thus providing a benefit for the future clinical therapy of pneumonia and medicine design.
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Purpose: To investigate the ability of qualitative Magnetic Resonance (MR) images features and quantitative Magnetic Resonance Imaging (MRI) texture features in the contrastive analysis between craniopharyngioma and meningioma. Method: A total number of 127 patients were included in this study (craniopharyngioma = 63; meningioma = 64). All the features analyzed in this study were acquired from preoperative MRI images. Qualitative MR images features were evaluated with chi-square tests or Fisher exact test, while MRI texture features were evaluated with the Mann-Whitney U test with the Benjamini-Hochberg method. Then binary logistic regression analysis for texture features was performed to evaluate their ability as independent predictors, and the diagnostic accuracy was calculated next for these texture features with high abilities as independent predictors using receiver operating characteristic (ROC) curves. Results: Four qualitative MR images features showed significant difference between craniopharyngioma and meningioma, but only cystic alteration could be considered as diagnostic independent predictors. Meanwhile, three quantitative parameters, histogram-based matrix- (HISTO-) Skewness, Grey-level co-occurrence matrix- (GLCM-) Contrast on contrast-enhanced images, and HISTO-Skewness on images of T2-weighted imaging (T2WI), showed promising abilities in the contrastive analysis. Besides, these texture features were found significantly to be relative to cystic alteration. Conclusion: MR images features and texture features were useful in the contrastive analysis of craniopharyngioma and meningioma. Furthermore, qualitative MR images features and MRI texture features could be related to each other.
Subject(s)
Craniopharyngioma/diagnostic imaging , Image Processing, Computer-Assisted , Magnetic Resonance Imaging , Meningeal Neoplasms/diagnostic imaging , Meningioma/diagnostic imaging , Pituitary Neoplasms/diagnostic imaging , Adolescent , Adult , Aged , Child , Child, Preschool , Craniopharyngioma/diagnosis , Diagnosis, Differential , Feasibility Studies , Female , Humans , Infant , Logistic Models , Male , Meningeal Neoplasms/diagnosis , Meningioma/diagnosis , Middle Aged , Pituitary Neoplasms/diagnosis , ROC Curve , Young AdultABSTRACT
OBJECTIVE: To investigate whether tumor texture features derived from preoperative T1-weighted magnetic resonance imaging (MRI) are associated with overall survival (OS) of patients with non-wingless-type (WNT)/non-sonic hedgehog (SHH) medulloblastoma. METHODS: We retrospectively reviewed 38 patients with non-WNT/non-SHH (encompassing group 3 and group 4) medulloblastoma treated with surgery in our institution from 2013 to 2016. All patients were followed-up for at least 2 years or until death. Primary tumor traditional parameters were evaluated, and texture features were extracted from preoperative T1-weighted MRI, including 4 features from the histogram matrix and 6 textures from the gray-level co-occurrence matrix (GLCM). Texture features were dichotomized into 2 subgroups based on their optimal cutoff values obtained from receiver operating characteristics curve analysis. Two-year OS was compared between the dichotomized subgroups using the Kaplan-Meier analysis and log-rank test. Multivariate Cox regression analysis was performed to determine independent prognostic factors. RESULTS: The therapy regimen was the only basic characteristic significantly related to 2-year OS (P = 0.015). Two features of the GLCM were shown to be significantly associated with 24-month OS. Multivariate Cox regression analysis revealed that GLCM homogeneity (adjusted hazard ratio, 0.145; P = 0.013) was an independent prognostic predictor for patients. CONCLUSIONS: Texture analysis on T1-weighted contrast-enhanced MRI potentially serves as a prognostic predictor of survival for patients with non-WNT/non-SHH medulloblastoma.
Subject(s)
Cerebellar Neoplasms/diagnostic imaging , Medulloblastoma/diagnostic imaging , Adolescent , Adult , Cerebellar Neoplasms/metabolism , Cerebellar Neoplasms/mortality , Child , Child, Preschool , Female , Humans , Infant , Magnetic Resonance Imaging , Male , Medulloblastoma/metabolism , Medulloblastoma/mortality , Prognosis , Retrospective Studies , Survival Rate , Young AdultABSTRACT
Purpose: The aim of this study was to test whether radiomics-based machine learning can enable the better differentiation between glioblastoma (GBM) and anaplastic oligodendroglioma (AO). Methods: This retrospective study involved 126 patients histologically diagnosed as GBM (n = 76) or AO (n = 50) in our institution from January 2015 to December 2018. A total number of 40 three-dimensional texture features were extracted from contrast-enhanced T1-weighted images using LIFEx package. Six diagnostic models were established with selection methods and classifiers. The optimal radiomics features were separately selected into three datasets with three feature selection methods [distance correlation, least absolute shrinkage and selection operator (LASSO), and gradient boosting decision tree (GBDT)]. Then datasets were separately adopted into linear discriminant analysis (LDA) and support vector machine (SVM) classifiers. Specificity, sensitivity, accuracy, and area under curve (AUC) of each model were calculated to evaluate their diagnostic performances. Results: The diagnostic performance of machine learning models was superior to human readers. Both classifiers showed promising ability in discrimination with AUC more than 0.900 when combined with suitable feature selection method. For LDA-based models, the AUC of models were 0.986, 0.994, and 0.970 in the testing group, respectively. For the SVM-based models, the AUC of models were 0.923, 0.817, and 0.500 in the testing group, respectively. The over-fitting model was GBDT + SVM, suggesting that this model was too volatile that unsuitable for classification. Conclusion: This study indicates radiomics-based machine learning has the potential to be utilized in clinically discriminating GBM from AO.
ABSTRACT
Introduction: Glioblastoma and anaplastic astrocytoma (ANA) are two of the most common primary brain tumors in adults. The differential diagnosis is important for treatment recommendations and prognosis assessment. This study aimed to assess the discriminative ability of texture analysis using machine learning to distinguish glioblastoma from ANA. Methods: A total of 123 patients with glioblastoma (n = 76) or ANA (n = 47) were enrolled in this study. Texture features were extracted from contrast-enhanced Magnetic Resonance (MR) images using LifeX package. Three independent feature-selection methods were performed to select the most discriminating parameters:Distance Correlation, least absolute shrinkage and selection operator (LASSO), and gradient correlation decision tree (GBDT). These selected features (datasets) were then randomly split into the training and the validation group at the ratio of 4:1 and were fed into linear discriminant analysis (LDA), respectively, and independently. The standard sensitivity, specificity, the areas under receiver operating characteristic curve (AUC) and accuracy were calculated for both training and validation group. Results: All three models (Distance Correlation + LDA, LASSO + LDA and GBDT + LDA) showed promising ability to discriminate glioblastoma from ANA, with AUCs ≥0.95 for both the training and the validation group using LDA algorithm and no overfitting was observed. LASSO + LDA showed the best discriminative ability in horizontal comparison among three models. Conclusion: Our study shows that MRI texture analysis using LDA algorithm had promising ability to discriminate glioblastoma from ANA. Multi-center studies with greater number of patients are warranted in future studies to confirm the preliminary result.