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1.
Chinese Pharmacological Bulletin ; (12): 499-505, 2024.
Article in Chinese | WPRIM | ID: wpr-1013642

ABSTRACT

Aim To investigate the molecular mechanism by which quercetin inhibits the malignant behavior of breast cancer cells. Methods Breast cancer cell lines MCF-7 and MB231 were used as the research models. Lentiviral transfection was employed to establish tumor cells with high expression of ERa and MAL-AT-1. The expression of MALAT-1 was assessed using RT-qPCR,and ERa expression was determined through Western blot. Subsequently, CCK-8 assay and colony formation assay were conducted to evaluate cell proliferation. PI staining and adenovirus transfection were performed to observe the inhibitory effects of quercetin on breast cancer cell proliferation. Results 17|3-es-tradiol ( E2 ) promoted the proliferation of MCF-7 breast cancer cells, while 5 jjunol L quercetin reversed the promoting effect of E2 on proliferation ( P 0. 05 ) . Quercetin had no effect on MB231 breast cancer cells. Overexpression of ERa significantly inhibited the pro-proliferative effect of E2 on MB231-ERa cells, and quercetin further suppressed this effect. Additionally , quercetin inhibited the expression of MALAT-1. However,this inhibitory effect was reversed by overexpression of MALAT-1, leading to enhanced cell proliferation , cell cycle progression, and clonal formation a-bility. Conclusions Quercetin exerts its anti-tumor effects on breast cancer cells by regulating MALAT-1, dependent on the presence of estrogen receptor. Quercetin shows potential as a therapeutic drug for breast cancer targeting the estrogen receptor.

2.
Journal of Pharmaceutical Practice ; (6): 78-81, 2024.
Article in Chinese | WPRIM | ID: wpr-1006845

ABSTRACT

Objective To establish method for simultaneous determination of hesperidin, cinnamaldehyde and eugenol in Chunyang Zhengqi capsules by high performance liquid chromatography. Methods The column was Agilent PorosheⅡ 120 EC-C18 (4.6 mm×150 mm, 4 μm). The mobile phase was acetonitrile-water with gradient elution. The column temperature was 35℃. The flow rate was 1.0 ml/min, and the detection wavelength was 284 nm. Results The methodological verification showed that hesperidin, cinnamaldehyde and eugenol had a good linearity (r≥0.999 9). The precisions were less than 2.0%. The average recovery was between 98.0% and 101.9%. The stability and repeatability of RSD were also less than 3.0%, which met the requirements of method validation. Conclusion The method is simple, stable, reproducible and accurate, which could be used to the quality control of Chunyang Zhengqi capsules.

3.
Acta Pharmaceutica Sinica B ; (6): 4202-4216, 2023.
Article in English | WPRIM | ID: wpr-1011176

ABSTRACT

Chronic pancreatitis (CP) is a progressive and irreversible fibroinflammatory disorder, accompanied by pancreatic exocrine insufficiency and dysregulated gut microbiota. Recently, accumulating evidence has supported a correlation between gut dysbiosis and CP development. However, whether gut microbiota dysbiosis contributes to CP pathogenesis remains unclear. Herein, an experimental CP was induced by repeated high-dose caerulein injections. The broad-spectrum antibiotics (ABX) and ABX targeting Gram-positive (G+) or Gram-negative bacteria (G-) were applied to explore the specific roles of these bacteria. Gut dysbiosis was observed in both mice and in CP patients, which was accompanied by a sharply reduced abundance for short-chain fatty acids (SCFAs)-producers, especially G+ bacteria. Broad-spectrum ABX exacerbated the severity of CP, as evidenced by aggravated pancreatic fibrosis and gut dysbiosis, especially the depletion of SCFAs-producing G+ bacteria. Additionally, depletion of SCFAs-producing G+ bacteria rather than G- bacteria intensified CP progression independent of TLR4, which was attenuated by supplementation with exogenous SCFAs. Finally, SCFAs modulated pancreatic fibrosis through inhibition of macrophage infiltration and M2 phenotype switching. The study supports a critical role for SCFAs-producing G+ bacteria in CP. Therefore, modulation of dietary-derived SCFAs or G+ SCFAs-producing bacteria may be considered a novel interventive approach for the management of CP.

4.
Acta Pharmaceutica Sinica ; (12): 3082-3089, 2023.
Article in Chinese | WPRIM | ID: wpr-999046

ABSTRACT

An LC-MS method with natural isotope abundance correction and a 1H NMR relative quantitative method were established to determine the deuterium incorporation of donafenib tosilate, a new deuterated drug molecule. First, the peak areas of isotopic impurities (non-deuterated and incompletely deuterated impurities) and deuterated drug were recorded through the single ion monitoring (SIM) mode of the established LC-MS method and then corrected in terms of the natural isotope abundance offered by ChemDraw soft, removing the nature isotope interference from 13C, 37Cl, etc. The corrected areas were subsequently used to calculate mol% of isotopologues (D0, D1, D2, D3) and Atom% D, namely, deuterium incorporation. In addition, a 1H qNMR experiment was conducted with the aromatic proton at δ 8.63 and the residual proton of isotopic impurities at δ 2.79 as quantitative peaks. The mixture of DMSO-d6 and D2O (10∶1) was employed as the solvent to change the spin-coupling between the residual proton and active hydrogen so that the residual proton could be measured as the single peak, and the sensitivity was greatly improved. The acquisition parameters were also optimized, and Atom% 1H and the deuterium incorporation were then calculated. The two methods were applied to samples of three commercial batches, and the testing results were almost consistent. Both methods proved accurate, sensitive, fast and independent of standard substances and accurate weighing, which could be applied to the determination of the deuterium incorporation of donafenib tosilate and provide a reference for other deuterated drugs.

5.
Journal of Sun Yat-sen University(Medical Sciences) ; (6): 958-964, 2023.
Article in Chinese | WPRIM | ID: wpr-998987

ABSTRACT

BackgroundType 1 diabetes is caused by a chronic immune response that destroys islet beta cells, resulting in elevated blood glucose. Mesenchymal stem cells can prevent and treat the development of diabetes and its complications. However, little is known about the effects and potential mechanisms of Gingival mesenchymal stem cells (GMSCs) in preventing diabetes. The aim of this study is to investigate the mechanism of GMSCs in preventing type 1 diabetes in mice and to find targets for clinical treatment of diabetes. MethodsWe injected human GMSCs into NOD mice to observe the trend of blood glucose, observed the survival of pancreatic β-cells by immunohistochemistry, and detected the change of immune cells in the spleen of mice by flow analysis. Finally, the immune cells in NOD mice were transfused into NOD-SCID mice to observe the onset of diabetes in NOD-SCID mice. ResultsGMSCs significantly reduced the incidence of diabetes in NOD mice, with 64% of control mice developing diabetes at 27 weeks of age compared with 35% in the GMSC group, P=0.013. The percentage of Follicular B cells(FO B cell) in the spleen of GMSCs-treated mice decreased from (52.2±4.1)% to (43.2±5.3)%, P=0.008, while other types of immune cells did not change significantly. The immunohistochemical results showed that GMSCs could effectively improve the survival of pancreatic β-cells, which could continuously produce insulin to control blood glucose. Finally, we found the spleen cells transfusion could prevent the development of diabetes in NOD-SCID mice. ConclusionGMSCs can reduce diabetes in mice by reducing FO B cells in the spleen.

6.
Clinical Psychopharmacology and Neuroscience ; : 544-558, 2023.
Article in English | WPRIM | ID: wpr-1000099

ABSTRACT

Objective@#Limited evidence exists regarding real-world 3-monthly paliperidone palmitate (PP3M) treatment retention and associated factors. @*Methods@#We conducted a retrospective, nationwide cohort study using the Taiwan National Health Insurance Research Database between October 2017 and December 2019. Adult patients with schizophrenia initiated on PP3M were enrolled. The primary outcomes were time to PP3M discontinuation, time to psychiatric hospitalization, and the proportions of patients receiving the next PP3M dose within 120 days among first-, second-, and third-dose completers. Key covariates included prior PP1M duration and adequate PP3M initiation. @*Results@#The PP3M treatment retention rates were 79.7%, 66.3%, and 52.5% after 6, 12, and 24 months, respectively, with 86.4%, 90.6%, and 90.0% of respective first-, second-, and third-dose completers receiving the next PP3M dose. Adequate PP3M initiation and prior PP1M treatment duration > 180 days were associated with favorable PP3M treatment retention. In multivariate analyses, PP1M durations of 180−360 days (adjusted relative risk [aRR], 1.76) or < 180 days (aRR, 2.79) were associated with PP3M discontinuation at the second dose. Inadequate PP3M initiation was associated with discontinuation at the third dose (aRR, 2.18). Patients fully adherent to PP3M treatment in the first year had a higher probability of being free from psychiatric hospitalization (86.7% at 2 years), compared with those partially adherent or non-adherent to PP3M in the first year. @*Conclusion@#Prior PP1M duration and adequate PP3M initiation are major factors affecting PP3M treatment retention. Higher PP3M treatment retention is associated with a lower risk of psychiatric hospitalization.

7.
Journal of Clinical Hepatology ; (12): 1482-1487, 2023.
Article in Chinese | WPRIM | ID: wpr-978811

ABSTRACT

Surgical operation is the main treatment method for pancreatic cancer, and in clinical practice, radical surgery for pancreatic cancer is often combined with superior mesenteric-portal vein confluence pancreaticoduodenectomy to achieve R0 resection. However, severe left-sided portal hypertension (LSPH) may occur after splenic vein dissection, resulting in a series of pathological changes such as congestive splenomegaly, thrombocytopenia, backflow obstruction of splenic vein, and gastrointestinal varices, and in some cases, it can lead to fatal gastrointestinal hemorrhage and hemorrhagic shock. Therefore, in order to better manage LSPH in clinical practice, this article systematically analyzes and reviews the pathogenesis, treatment regimens, and control strategies of LSPH after combined superior mesenteric-portal vein confluence pancreaticoduodenectomy and put forward corresponding suggestions based on current studies.

8.
Journal of Geriatric Cardiology ; (12): 801-812, 2023.
Article in English | WPRIM | ID: wpr-1010212

ABSTRACT

BACKGROUND@#Myocardial ischemia-reperfusion (I/R) is a serious and irreversible injury. Bone marrow-derived mesenchymal stem cells (MSCs) is considered to be a potential therapy for I/R injury due to the paracrine effects. High-mobility group box 1 (HMGB1) is a novel mediator in MSC and regulates the response of inflammation injury. Signal Transduction and Transcription Activator 3 (STAT3) is a critical transcription factor and important for release of paracrine factors. However, the relationship between HMGB1 and STAT3 in paracrine effect of MSC remains unknown.@*METHODS@#In vitro, hypoxia/reoxygenation injury model was established by AnaeroPack System and examined by Annexin V flow cytometry, CCK8 assay and morphology observation. Detection of apoptotic proteins and protein expression of HMGB1 and STAT3 by Western blot.@*RESULTS@#The conditioned medium of MSCs with or without LPS pretreatment was cocultured with H9C2 cells for 24 h before hypoxia treatment and MSC showed obvious cardiomyocytes protect role, as evidence by decreased apoptosis rate and improved cells viability, and LPS pretreated MSC exhibited better protect role than untreated MSC. However, such effect was abolished in HMGB1 deficiency group, silencing HMGB1 decreased the secretion of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin growth factor (IGF), cell viability, and the expression of STAT3. Furthermore, STAT3 silence attenuated the protective effect of LPS in MSC.@*CONCLUSIONS@#These findings suggested that LPS improved MSC-mediated cardiomyocytes protection by HMGB1/STAT3 signaling.

9.
Asian Journal of Andrology ; (6): 103-112, 2023.
Article in English | WPRIM | ID: wpr-970996

ABSTRACT

This study aims to characterize the cell atlas of the epididymis derived from a 46,XY disorders of sex development (DSD) patient with a novel heterozygous mutation of the nuclear receptor subfamily 5 group A member 1 (NR5A1) gene. Next-generation sequencing found a heterozygous c.124C>G mutation in NR5A1 that resulted in a p.Q42E missense mutation in the conserved DNA-binding domain of NR5A1. The patient demonstrated feminization of external genitalia and Tanner stage 1 breast development. The surgical procedure revealed a morphologically normal epididymis and vas deferens but a dysplastic testis. Microfluidic-based single-cell RNA sequencing (scRNA-seq) analysis found that the fibroblast cells were significantly increased (approximately 46.5%), whereas the number of main epididymal epithelial cells (approximately 9.2%), such as principal cells and basal cells, was dramatically decreased. Bioinformatics analysis of cell-cell communications and gene regulatory networks at the single-cell level inferred that epididymal epithelial cell loss and fibroblast occupation are associated with the epithelial-to-mesenchymal transition (EMT) process. The present study provides a cell atlas of the epididymis of a patient with 46,XY DSD and serves as an important resource for understanding the pathophysiology of DSD.


Subject(s)
Male , Humans , Epididymis , Disorder of Sex Development, 46,XY/genetics , Disorders of Sex Development , Mutation , Mutation, Missense , Steroidogenic Factor 1/genetics
10.
Chinese journal of integrative medicine ; (12): 434-440, 2023.
Article in English | WPRIM | ID: wpr-982290

ABSTRACT

OBJECTIVE@#To investigate the effect and potential mechanism of dihydromyricetin (Dmy) on H9C2 cell proliferation, apoptosis, and autophagy.@*METHODS@#H9C2 cells were randomly divided into 7 groups, namely control, model, EV (empty pCDH-CMV-MCS-EF1-CopGFP-T2A-Puro vector), IV (circHIPK3 interference), Dmy (50 µ mol/L), Dmy+IV, and Dmy+EV groups. Cell proliferation and apoptosis were detected by cell counting kit-8 assay and flow cytometry, respectivley. Western blot was used to evaluate the levels of light chain 3 II/I (LC3II/I), phospho-phosphoinositide 3-kinase (p-PI3K), protein kinase B (p-AKT), and phospho-mammalian target of rapamycin (p-mTOR). The level of circHIPK3 was determined using reverse transcriptase polymerase chain reaction. Electron microscopy was used to observe autophagosomes in H9C2 cells.@*RESULTS@#Compared to H9C2 cells, the expression of circHIPK in H9C2 hypoxia model cells increased significantly (P<0.05). Compared to the control group, the cell apoptosis and autophagosomes increased, cell proliferation rate decreased significantly, and the expression of LC3 II/I significantly increased (all P<0.05). Compared to the model group, the rate of apoptosis and autophagosomes in IV, Dmy, and Dmy+IV group decreased, the cell proliferation rate increased, and the expression of LC3 II/I decreased significantly (all P<0.05). Compared to the control group, the expressions of p-PI3K, p-AKT, and p-mTOR in the model group significantly reduced (P<0.05), whereas after treatment with Dmy and sh-circHIPK3, the above situation was reversed (P<0.05).@*CONCLUSION@#Dmy plays a protective role in H9C2 cells by inhibiting circHIPK expression and cell apoptosis and autophagy, and the mechanism may be related to PI3K/AKT/mTOR pathway.


Subject(s)
Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Phosphatidylinositol 3-Kinases/metabolism , TOR Serine-Threonine Kinases/metabolism , Apoptosis , Autophagy
11.
Chinese Medical Journal ; (24): 1459-1467, 2023.
Article in English | WPRIM | ID: wpr-980912

ABSTRACT

BACKGROUND@#Endocrine therapy (ET) and ET-based regimens are the preferred first-line treatment options for hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (HR+/HER2- MBC), while chemotherapy (CT) is commonly used in clinical practice. The aim of this study was to investigate the efficacy and clinical outcome of ET and CT as first-line treatment in Chinese patients with HR+/HER2- MBC.@*METHODS@#Patients diagnosed with HR+/HER2-MBC between January 1st, 1996 and September 30th, 2018 were screened from the Chinese Society of Clinical Oncology Breast Cancer database. The initial and maintenance first-line treatment, progression-free survival (PFS), and overall survival (OS) were analyzed.@*RESULTS@#Among the 1877 included patients, 1215 (64.7%) received CT and 662 (35.3%) received ET as initial first-line treatment. There were no statistically significant differences in PFS and OS between patients receiving ET and CT as initial first-line treatment in the total population (PFS: 12.0 vs. 11.0 months, P = 0.22; OS: 54.0 vs . 49.0 months, P =0.09) and propensity score matched population. For patients without disease progression after at least 3 months of initial therapy, maintenance ET following initial CT (CT-ET cohort, n = 449) and continuous schedule of ET (ET cohort, n = 527) had longer PFS than continuous schedule of CT (CT cohort, n = 406) in the total population (CT-ET cohort vs. CT cohort: 17.0 vs . 8.5 months; P <0.01; ET cohort vs . CT cohort: 14.0 vs . 8.5 months; P <0.01) and propensity score matched population. OS in the three cohorts yielded the same results as PFS.@*CONCLUSIONS@#ET was associated with similar clinical outcome to CT as initial first-line treatment. For patients without disease progression after initial CT, switching to maintenance ET showed superiority in clinical outcome over continuous schedule of CT.


Subject(s)
Humans , Female , Breast Neoplasms/metabolism , Receptor, ErbB-2/metabolism , Progression-Free Survival , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Disease Progression , Treatment Outcome
12.
Journal of Experimental Hematology ; (6): 1820-1824, 2023.
Article in Chinese | WPRIM | ID: wpr-1010044

ABSTRACT

OBJECTIVE@#To investigate the changes of platelet count (PLT), plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) before and after apheresis platelet transfusion, the correlation between the parameters and their clinical significance.@*METHODS@#A total of 38 patients who received apheresis platelet transfusion were selected, their results of blood routine test closest to the time point of apheresis platelet transfusion were consulted from hospital information system and the changes of PLT, PCT, MPV and PDW were compared before and after transfusion. The correlation between above parameters was analyzed. The correlation of body mass index (BMI) with the increased multiple and increased value after platelet infusion was also analyzed.@*RESULTS@#Compared with pre-infusion, PLT and PCT significantly increased (both P <0.001) while MPV and PDW showed no significant difference after apheresis platelet transfusion (P >0.05). The difference of PLT and PCT before and after apheresis platelet transfusion had no correlation with PLT and PCT before transfusion (r =0.002, r =0.001), while the difference of MPV and PDW was negatively correlated with MPV and PDW before transfusion (r =-0.462, r =-0.610). The PLT growth rate was positively correlated with PCT growth rate before and after apheresis platelet transfusion (r =0.819). BMI was positively correlated with the increased multiple of PLT after infusion (r =0.721), but not with the increased value of PLT after infusion (r =0.374).@*CONCLUSION@#Apheresis platelet transfusion can cause platelet parameters change and shows different characteristics. Characteristic changes of platelet parameters and their correlation can be used as reference indices to evaluate the efficacy of apheresis platelet transfusion.


Subject(s)
Humans , Mean Platelet Volume , Platelet Transfusion , Blood Platelets , Platelet Count/methods , Blood Component Removal
13.
Journal of Sun Yat-sen University(Medical Sciences) ; (6): 403-415, 2023.
Article in Chinese | WPRIM | ID: wpr-973236

ABSTRACT

ObjectiveTo analyze the induction effect of Fusobacterium nucleatum (Fn) on endoplasmic reticulum stress-related proteins Glucose-regulating protein 78(GRP78) and X-box binding protein 1(XBP1) in esophageal squamous cell carcinoma (ESCC), and to explore its potential mechanism and clinical significance. MethodsESCC cells KYSE150 and KYSE140 were infected with Fn for 12 h, 24 h and 48 h. The oxidative stress indexes (ROS, MDA and SOD) and the expression of GRP78 and XBP1 in each group were detected by oxidative stress index kit and Western blot. The experiment was divided into Fn groups, Fn+siNC1 groups, Fn+siGRP78 groups, Fn+siNC2 groups and Fn+siXBP1 groups; the oxidative stress indexes, paclitaxel (PTX) response efficacy, abilities of proliferation, invasion and metastasis in each group were compared. The infection of Fn and the expression of GRP78 and XBP1 in 234 ESCC and paracancerous tissues were detected by RNA scope and immunohistochemistry. The correlation between each factor and clinicopathological characteristics of patients was analyzed by Chi-square test. The influence of each factor on the survival of patients was compared by Kaplan-meier survival estimate. ResultsCompared with Fn uninfected KYSE150 and KYSE140 cells, the content of ROS and MDA was gradually increased, the activity of SOD was gradually decreased, and the expression of GRP78 and XBP1 was gradually increased in Fn infected groups (12 h, 24 h and 48 h) (P < 0.05). Compared with Fn groups, Fn+siNC1 groups, and Fn+siNC2 groups, ROS and MDA contents were decreased, SOD activity was increased, PTX response efficacy was enhanced, and abilities of proliferation, invasion and metastasis were decreased in Fn+siGRP78 and Fn+siXBP1 groups (P < 0.05). The rates of Fn, GRP78 and XBP1 in ESCC tissues were 43.16%, 69.66% and 60.68%, respectively. And the three indexes were significantly consistent (P < 0.05). The patients with positive Fn infection and high expression of GRP78 and XBP1 were mostly males with a history of smoking and drinking, and the tumor differentiation degree was low, the invasion degree was deep, the lymph node metastasis rate was high, and the clinical stage was mostly stage Ⅲ/Ⅳ. The 5-year survival time of patients with above positive indexes was shortened (P < 0.05). ConclusionsFn could induce endoplasmic reticulum stress by inducing the high expression of GRP78 and XBP1, and promote the malignant evolution of ESCC.

14.
Chinese Journal of Otorhinolaryngology Head and Neck Surgery ; (12): 126-132, 2023.
Article in Chinese | WPRIM | ID: wpr-971419

ABSTRACT

Objective: To introduce a classification of alar retraction, and to discuss the therapeutic strategy of alar retraction with cartilage graft and the satisfaction evaluation of patients after operation. Methods: A retrospective analysis was performed on 88 patients with alar retraction admitted to the Department of Plastic and Aesthetic (Burn) Surgery, the Second Xiangya Hospital of Central South University from January 2015 to December 2020, including 20 males and 68 females, aged 20 to 48 years, with an average age of 28.98 years. All patients underwent external rhinoplasty according to a series of treatment plans determined by the classification of alar retraction based on nostril exposure. Visual Analogue Scale (VAS) and Rhinoplasty Outcomes Evaluation (ROE) were used to conduct satisfaction survey before and 12 months after operation. Wilcoxon signed-rank test was used to analyze patient satisfaction. Results: A total of 88 patients were included in this study. According to the classification of alar retraction based on nostril exposure, 45 cases were mild, 23 cases were moderate, and 20 cases were severe. There were 16 cases of unilateral and 72 cases of bilateral alar retraction. The patients were followed up for 12 to 18 months, with an average of 13.37 months. The VAS score and ROE score after each type of surgery were higher than those before surgery, with statistically significant (all P<0.05). Among them, the difference in VAS score (6.75±1.29) and in ROE satisfaction (67.70±7.38) of patients with severe alar retraction were the most significant improvement. Conclusion: The classification of alar retraction based on nostril exposure in the frontal view can comprehensively evaluate the severity of alar retraction, and makes the treatment algorithms systematic and comprehensive. The satisfaction of patients is relatively high.


Subject(s)
Male , Female , Humans , Adult , Rhinoplasty , Retrospective Studies , Patient Satisfaction , Treatment Outcome , Esthetics , Nose/surgery
15.
Journal of Movement Disorders ; : 91-94, 2023.
Article in English | WPRIM | ID: wpr-967589

ABSTRACT

KMT2B-linked dystonia (DYT-KMT2B) is a childhood-onset dystonia syndrome typically beginning in the lower limbs and progressing caudocranially to affect the upper limbs with eventual prominent craniocervical involvement. Despite its recent recognition, it now appears to be one of the more common monogenic causes of dystonia syndromes. Here, we present an atypical case of DYT-KMT2B with oromandibular dystonia as the presenting feature, which remained restricted to this region three decades after symptom onset. This appears to be the first reported case of DYT-KMT2B from Southeast Asia and provides further supporting evidence for the pathogenic impact of the KMT2B c.6210_6213delTGAG variant.

16.
Clinical and Molecular Hepatology ; : S228-S243, 2023.
Article in English | WPRIM | ID: wpr-966582

ABSTRACT

Nonalcoholic steatohepatitis (NASH) is an aggressive form of nonalcoholic fatty liver disease (NAFLD) characterized by steatosis-associated inflammation and liver injury. Without effective treatment or management, NASH can have life-threatening outcomes. Evaluation and identification of NASH patients at risk for adverse outcomes are therefore important. Key issues in screening NASH patients are the assessment of advanced fibrosis, differentiation of NASH from simple steatosis, and monitoring of dynamic changes during follow-up and treatment. Currently, NASH staging and evaluation of the effectiveness for drugs still rely on pathological diagnosis, despite sample error issues and the subjectivity associated with liver biopsy. Optimizing the pathological assessment of liver biopsy samples and developing noninvasive surrogate methods for accessible, accurate, and safe evaluation are therefore critical. Although noninvasive methods including elastography, serum soluble biomarkers, and combined models have been implemented in the last decade, noninvasive diagnostic measurements are not widely applied in clinical practice. More work remains to be done in establishing cost-effective strategies both for screening for at-risk NASH patients and identifying changes in disease severity. In this review, we summarize the current state of noninvasive methods for detecting steatosis, steatohepatitis, and fibrosis in patients with NASH, and discuss noninvasive assessments for screening at-risk patients with a focus on the characteristics that should be monitored at follow-up.

18.
Chinese Journal of Biochemistry and Molecular Biology ; (12): 990-998, 2022.
Article in Chinese | WPRIM | ID: wpr-1015773

ABSTRACT

O⁃GlcNAcylation is an O⁃linked⁃β⁃N⁃acetylglucosamine modification attached to the hydroxyl group of serine or threonine residue within the nuclear or cytoplasmic proteins. O⁃GlcNAcylation profoundly influences important biological events, including kinase activity, transcription and translation, and protein degradation. However, there are few summarized reviews on how O⁃GlcNAcylation modulates signaling pathways associated with inflammatory responses. Due to the attachment and removal of the sugar group catalyzed by O⁃GlcNAc transferase and O⁃GlcNAcase, O⁃GlcNAcylation cycles rapidly with a short half⁃life time (within minutes). Therefore, O⁃GlcNAcylation plays a crucial role in various signaling pathways via intricate cross⁃talking with other post⁃translational modifications of protein, such as phosphorylation, acetylation, ubiquitylation, and methylation. Currently, most researchers focused on the Toll⁃like receptor (TLR)⁃initiated NF⁃κB signaling when it comes to the relationship between O⁃GlcNAcylation and inflammation. Evidence has shown that O⁃GlcNAcylation at T352 or at T305 on p65 promotes its nuclear translocation activity, while O⁃GlcNAcylation at S536 blocks the activation of p65 by competing with phosphorylation. Meanwhile, O⁃GlcNAcylation modulates upstream and downstream regulators of NF⁃κB and then governs the polarization of M1/ M2 macrophage and the progress of inflammation reactions. Furthermore, O⁃GlcNAcylation indirectly participates in the kinase activation of MAPKs by interfering with the proteins at the upper reaches (i. e. MEK2 and Ras proteins). Besides, O⁃GlcNAcylation has a profound influence on multiple kinases of PI3K/ AKT signaling. Nevertheless, O⁃GlcNAcylation manipulates inflammation⁃associated transcriptional factors on the JAK/ STAT pathway. Comparatively, the involved signaling transduction for the inflammatory response in vivo is far more complicated and multidimensional than that in vitro. And O⁃GlcNAcylation is widely involved with the onset and development of inflammatory diseases located at the pancreas, liver, lung, gut, and adipose tissues. Novel research has firstly found that gut bacteria expressing O⁃GlcNAcase⁃like hydrolases exert potent prevention on mouse colitis induced by different chemical drugs, which indicates the mediating role of O⁃GlcNAcylation in mutual interactions between gut microbiota and host inflammation. In summary, recent findings provided a novel strategy for preventing and treating inflammatory diseases by targeting O⁃GlcNAcylation.

19.
Chinese Pharmacological Bulletin ; (12): 85-90, 2022.
Article in Chinese | WPRIM | ID: wpr-1014176

ABSTRACT

Aim To evaluate the effects of different doses of IL-36Ra on pain behavior and the polarization of spinal A1 astrocytes in mice with inflammatory pain.Methods A total of 32 male C57BL/6 mice were divided into four groups: CFA+Saline group, CFA+IL-36Ra 50 ng group, CFA+IL-36Ra 100 ng group and CFA+IL-36Ra 200 ng group by random grouping.The inflammatory pain model was established by injection of complete Freund's adjuvant(CFA)into the plantar surface of the right hind paw of mice.The drugs were given daily from the 1st day to the 7th day after CFA injection in each group by intrathecal injection.The changes in the mechanical withdrawal threshold(MWT)and the radiant heat stimulating paw withdrawal latency(PWL)of the mice were detected before and 1, 3, 5 and 7 days after the CFA injection.Reverse transcription polymerase chain reaction was used to detect the expression changes of A1 and A2 astrocyte markers after IL-36Ra treatment.Immunohistochemistry was used to test the effect of IL-36Ra on the co-expression level of A1 astrocyte marker C3 and GFAP in the spinal dorsal horn.Results MWT and PWL of the ipsilateral paw significantly decreased after the CFA injection, and IL-36Ra(100 ng, 200 ng)treatment could significantly improve the mechanical allodynia and thermal hyperalgesia of CFA mice.After treatment for 7 days, IL-36Ra 200 ng successfully reversed the increase of GFAP and Lcn2 expression in the spinal cord of CFA mice, which demonstrated IL-36Ra could inhibit the activation of astrocytes.IL-36Ra significantly inhibited the expression of A1 astrocyte maker Serping1, H2-T23 in spinal cord but showed no effects on the expression of A2 astrocytes marker with each dose.Furthermore, IL-36Ra inhibited the expression of C3 within the astrocytes in the spinal dorsal horn of CFA mice.Conclusion IL-36Ra attenuates the inflammatory pain via inhibiting the polarization of A1 reactive astrocytes in the spinal cord of mice with inflammatory pain.

20.
Chinese Pharmacological Bulletin ; (12): 1231-1238, 2022.
Article in Chinese | WPRIM | ID: wpr-1014039

ABSTRACT

Aim To explore the mechanism of Huoxue Jiedu Chinese Herbal Compatibility (angelica sinensis - lonicerae japonicae flos ) in anti-atherosclerosis by means of network pharmacology and molecular rloe- king.Methods The effective eomponents and related targets of angelica sinensis and lonicerae japonicae flos were sereened by the TCMSP database, and the dis¬ease related targets of atheroselerosis were obtained by using the Gene Cards database, DrugBank database and OMIM database.The common targets were ob¬tained by Venny2.1 , an online mapping tool.The pro- tein-protein interaction ( PPI) network was established by String 11.0, and the common target was analyzed by gene ontology(GO) enrichment analysis and kvoto en- cyelopedia of genes and genomes ( KEGG) enrichment analysis using metascape online platform.Cyto- seape3.8.2 was used to construct the " active ingredi¬ent-active target-pathway network map.Finally AutoDock and PyMOL softwares were applied for mo¬lecular docking.Results A total of 31 active compo¬nents of angelica sinensis-lonicerae japonicae flos com¬ patibility and 509 component targets were screened.Hie number of intersection targets with atherosclerosis was 210.GO function enrichment analysis revealed 2 961 biological process items and 242 molecular func¬tion items.KEGG pathway enrichment screened 250 signaling pathways, PI3K-Akt signaling pathway, MAPK signaling pathway, and fluid shear stress and atherosclerosis were the key pathways.Molecular doc¬king results showed that beta-sitosterol, ferulic acid, rutin, luteolin, quercetin could bind stably with MAPK (-1,-3), AKT1, PRKC ( A, B).Conclusions Huoxue Jiedu Chinese Herbal Compatibility ( angelica sinensis -lonicerae japonicae flos) containing multiple active ingredients may play an anti-atherosclerosis role through the signaling pathways of MAPK, P13K-Akt and PRKC, reflecting the advantages of the treatment of activating blood circulation and detoxification of tra¬ditional Chinese medicine in anti-atherosclerosis.

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