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1.
Acta Pharmaceutica Sinica ; (12): 2130-2138, 2023.
Article in Chinese | WPRIM | ID: wpr-999106

ABSTRACT

Puromycin-sensitive aminopeptidase (PSAP) belongs to the M1 family of aminopeptidases, characterized by the N-terminal substrate binding sequence GAMEN, the enzyme activity center HEXXH(X)18E motif, and the C-terminal ERAP-1-like superfamily structural domain. Encoded by the gene NPEPPS located at 17q21.32, PSAP consists of 919 amino acids and is widely distributed throughout the human body, with the highest expression in the brain, followed by the heart and skeletal muscle. It is also found in the liver, renal tubular epithelium, small intestine, large intestine epithelium, and gastric epithelial cells. PSAP primarily relies on its aminopeptidase hydrolytic activity to remove toxic protein aggregates such as Tau, poly Q, and Cu, Zn-superoxide dismutase 1, making it an important factor in the development of diseases such as Alzheimer's disease, Huntington's chorea, and tumors. Existing PSAP inhibitors include bestatin, amastatin, leuhistin, actinonin, and purinomycin, some of which are already available or in clinical trials. This review provides an overview of the structural and biological functions of M1 family aminopeptidases, with a focus on PSAP, to facilitate further research and targeted drug development.

2.
Chinese Journal of School Health ; (12): 1708-1712, 2023.
Article in Chinese | WPRIM | ID: wpr-998890

ABSTRACT

Objective@#To determine the association between anthropometric parameters and 20 meter shuttle run test (20 m SRT) score among children and adolescents.@*Methods@#The convenient sampling method was conducted to select 3 192 primary and secondary school students in Baoan District, Shenzhen, based on the street school types school from April to May 2019. Height, weight, 20 m SRT score and general demographic indicators were assessed and collected. Individuals were divided into two groups based on the dose response correlation between different anthropometric parameters (the Z score of height, weight and BMI) and 20 m SRT score analyzed with the restricted cubic spline. The association between the Z score of height and 20 m SRT score was further analyzed using the Spearman correlation analysis. Logistic regression analysis was used to analyze separately the relationship different anthropometric parameters and 20 m SRT score.@*Results@#The Z value of weight and 20 m SRT score showed a non linear dose response association ( P <0.01), the significant but weak linear correlation between the Z value of height and 20 m SRT score ( r=0.06, P <0.05). The prevalence rate on the low level of the Z value of 20 m SRT score in 3 192 children and adolescents was 44.7%, and the gender ( χ 2=14.02, P <0.01) and grade difference ( χ 2=93.28, P <0.01) were both statistically significant. There was no significant relationship between the Z value of height and 20 m SRT score grade among total population, different genders and different grades ( P > 0.05). Compared with the reference group on the Z value of weight ≤-0.23, individuals with the Z value of weight >-0.23 had the low level of 20 m SRT score ( OR =0.61, P <0.05). Compared with the reference group on the Z value of BMI ≤ 0.25, individuals with the Z value of weight >0.25 had the low level of 20 m SRT score ( OR =0.45, P <0.05). Stratified for gender and grade, the above significant relationship on the Z value of weight, Z value of BMI and 20 m SRT score were still observed ( P <0.01).@*Conclusions@#The higher height Z value shows on correlations with 20 m SRT score, but the positive association is found between weight and BMI Z value and the 20 m SRT score. The cardiopulmonary fitness improvement may be more effective among children and adolescents when tuking weight and BMI Z scores into consideration.

3.
Journal of Zhejiang University. Medical sciences ; (6): 185-194, 2023.
Article in English | WPRIM | ID: wpr-982034

ABSTRACT

OBJECTIVES@#To investigate the effects and molecular mechanisms of asiatic acid on β-cell function in type 2 diabetes mellitus (T2DM).@*METHODS@#The T2DM model was established by high fat diet and streptozotocin injection in ICR mice, and the effects of asiatic acid on glucose regulation were investigated in model mice. The islets were isolated from palmitic acid-treated diabetic mice. ELISA was used to detect the glucose-stimulated insulin secretion, tumor necrosis factor (TNF)-α and interleukin (IL)-6. ATP assay was applied to measure ATP production, and Western blotting was used to detect protein expression of mature β cell marker urocortin (Ucn) 3 and mitofusin (Mfn) 2. The regulatory effects of asiatic acid on glucose-stimulated insulin secretion (GSIS) and Ucn3 expression were also investigated after siRNA interference with Mfn2 or treatment with TNF-α.@*RESULTS@#Asiatic acid with the dose of 25 mg·kg-1·d-1 had the best glycemic control in T2DM mice and improved the homeostasis model assessment β index. Asiatic acid increased the expression of Mfn2 and Ucn3 protein and improved the GSIS function of diabetic β cells in vitro and in vivo (both P<0.05). Moreover, it improved the ATP production of islets of T2DM mice in vitro (P<0.05). Interfering Mfn2 with siRNA blocked the up-regulation of Ucn3 and GSIS induced by asiatic acid. Asiatic acid inhibited islet TNF-α content and increased Mfn2 and Ucn3 protein expression inhibited by TNF-α.@*CONCLUSIONS@#Asiatic acid improves β cell insulin secretion function in T2DM mice by maintaining the β cell maturity, which may be related to the TNF-α/Mfn2 pathway.


Subject(s)
Mice , Animals , Insulin Secretion , Diabetes Mellitus, Type 2/drug therapy , Islets of Langerhans/metabolism , Tumor Necrosis Factor-alpha/metabolism , Insulin/therapeutic use , Diabetes Mellitus, Experimental , Mice, Inbred ICR , Glucose/therapeutic use , Interleukin-6/metabolism , RNA, Small Interfering/pharmacology , Adenosine Triphosphate , GTP Phosphohydrolases/therapeutic use
4.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 104-111, 2023.
Article in Chinese | WPRIM | ID: wpr-973138

ABSTRACT

ObjectiveTo observe the pharmacodynamic effects of Cinnamomi Cortex on the incretin effect in the rat model of diabetes mellites (DM) induced by streptozotocin (STZ) and explore the underlying mechanism from glucagon-like peptide-1 (GLP-1) and dipeptidyl peptidase-4 (DPP-4). MethodForty SD rats were randomly assigned into blank, model, sitagliptin (0.1 g·kg-1), and low- and high-dose Cinnamomi Cortex (0.45 and 0.9 g·kg-1, respectively) groups. The DM rat model was established by a high-fat diet combined with intraperitoneal injection of 40 mg·kg-1 STZ in other groups except the blank group. The intervention lasted for 8 weeks. The status, body weight, water intake, food intake, and fasting blood glucose (FBG) of the rats were observed and determined. Hematoxylin-eosin staining was employed to reveal the pathological changes of the pancreas, and immunohistochemistry to detect the expression of glucagon in the pancreas. Biochemical assay was employed to measure the serum levels of lipid metabolism indexes such as total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL). Enzyme-linked immunosorbent assay was employed to determine the levels of glycosylated hemoglobin, insulin, glucagon, GLP-1, and glucose-dependent insulinotropic polypeptide (GIP) in rat serum, and Western blot to determine the protein levels of GLP-1 and DPP-4 in the pancreas. ResultAfter 8 weeks of intervention, the model group showed higher body weight, FBG, TC, TG, LDL, glycosylated hemoglobin, glucagon, insulin, and insulin resistance index and lower HDL, GLP-1, and GIP than the blank group (P<0.05, P<0.01). The Cinnamomi Cortex groups showed lower body weight, FBG, TC, TG, LDL, glycosylated hemoglobin, glucagon, insulin, and insulin resistance index and higher HDL, GLP-1, and GIP than the model group (P<0.05, P<0.01). The Cinnamomi Cortex groups showed recovered morphology of islet cells and no nucleus aggregation. Compared with the model group, the Cinnamomi Cortex groups showed declined levels of glucagon in the center of islet cells. Compared with the blank group, the model group showed up-regulated protein level of DPP-4 and down-regulated protein level of GLP-1 (P<0.01). Compared with the model group, the high-dose Cinnamomi Cortex groups showed down-regulated protein level of DPP-4 and up-regulated protein level of GLP-1 (P<0.05). ConclusionCinnamomi Cortex may reduce blood glucose and improve incretin effect to lower the blood glucose level by regulating DPP-4 and GLP-1 in DM rats.

5.
Acta Physiologica Sinica ; (6): 339-350, 2023.
Article in Chinese | WPRIM | ID: wpr-981010

ABSTRACT

This paper aimed to investigate the role and potential mechanism of p53 on primordial follicle activation. Firstly, the p53 mRNA expression in the ovary of neonatal mice at 3, 5, 7 and 9 days post-partum (dpp) and the subcellular localization of p53 were detected to confirm the expression pattern of p53. Secondly, 2 dpp and 3 dpp ovaries were cultured with p53 inhibitor Pifithrin-μ (PFT-μ, 5 μmol/L) or equal volume of dimethyl sulfoxide for 3 days. The function of p53 in primordial follicle activation was determined by hematoxylin staining and whole ovary follicle counting. The proliferation of cell was detected by immunohistochemistry. The relative mRNA levels and protein levels of the key molecules involved in the classical pathways associated with the growing follicles were examined by immunofluorescence staining, Western blot and real-time PCR, respectively. Finally, rapamycin (RAP) was used to intervene the mTOR signaling pathway, and ovaries were divided into four groups: Control, RAP (1 μmol/L), PFT-μ (5 μmol/L), PFT-μ (5 μmol/L) + RAP (1 μmol/L) groups. The number of follicles in each group was determined by hematoxylin staining and whole ovary follicle counting. The results showed that the expression of p53 mRNA was decreased with the activation of primordial follicles in physiological condition. p53 was expressed in granulosa cells and oocyte cytoplasm of the primordial follicles and growing follicles, and the expression of p53 in the primordial follicles was higher than that in the growing follicles. Inhibition of p53 promoted follicle activation and reduced the primordial follicle reserve. Inhibition of p53 promoted the proliferation of the granulosa cells and oocytes. The mRNA and protein expression levels of key molecules in the PI3K/AKT signaling pathway including AKT, PTEN, and FOXO3a were not significantly changed after PFT-μ treatment, while the expression of RPS6/p-RPS6, the downstream effectors of the mTOR signaling pathway, was upregulated. Inhibition of both p53 and mTOR blocked p53 inhibition-induced primordial follicle activation. Collectively, these findings suggest that p53 may inhibit primordial follicle activation through the mTOR signaling pathway to maintain the primordial follicle reserve.


Subject(s)
Female , Animals , Mice , Tumor Suppressor Protein p53/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Hematoxylin , Signal Transduction/physiology , TOR Serine-Threonine Kinases , Sirolimus , RNA, Messenger
6.
Chinese Journal of Preventive Medicine ; (12): 1082-1095, 2023.
Article in Chinese | WPRIM | ID: wpr-985477

ABSTRACT

During the global efforts to prevent and control the COVID-19 pandemic, extensive research and development of SARS-CoV-2 vaccines using various technical approaches have taken place. Among these, vaccines based on adenovirus vector have gained substantial knowledge and experience in effectively combating potential emerging infectious diseases, while also providing novel ideas and methodologies for vaccine research and development (R&D). This comprehensive review focuses on the adenovirus vector technology platform in vaccine R&D, emphasizing the importance of mucosal immunity induced by adenoviral vector-based vaccine for COVID-19 prevention. Furthermore, it analyzes the key technical challenges and obstacles encountered in the development of vaccines based on the adenovirus vector technology platform, with the aim of providing valuable insights and references for researchers and professionals in related fields.


Subject(s)
Humans , COVID-19 Vaccines , Pandemics/prevention & control , COVID-19/prevention & control , SARS-CoV-2/genetics , Viral Vaccines/genetics , Adenoviridae/genetics , Technology
7.
Chinese Journal of Preventive Medicine ; (12): 732-735, 2023.
Article in Chinese | WPRIM | ID: wpr-985465

ABSTRACT

This study followed up the immune memory after 3-dose revaccination among infants with non-and low-response following primary hepatitis B (HepB) vaccination. About 120 children without self-booster doses were finally included who had anti-HBs<10 mIU/ml (anti-HBs negative) at the time of follow-up, of whom 86 children completed blood sampling and anti-HBs testing. Before the challenge dose, all 86 children were negative for anti-HBs, and the GMC of anti-HBs was<10 mIU/ml. The seropositive conversion rate of anti-HBs was 100% and the GMC of anti-HBs was 886.11 (95%CI: 678.15-1 157.84) mIU/ml after the challenge dose. Compared with those with GMC<7 mIU/ml before the challenge dose, infants with GMC>7 mIU/ml had a higher anti-HBs level after the challenge dose. The β value (95%CI) was 0.82 (0.18-1.46) (P=0.012). Compared with those with GMC<1 000 mIU/ml at primary vaccination, infants with GMC≥1 000 mIU/ml had a higher anti-HBs level after the challenge dose. The β value (95%CI) was 0.78 (0.18-1.38)(P=0.012). The results showed a stronger immune memory was found at 9 years after revaccination among infants with non-and low-response to HepB.


Subject(s)
Child , Humans , Infant , Hepatitis B Vaccines , Immunization, Secondary , Hepatitis B Surface Antigens , Immunologic Memory , Follow-Up Studies , Vaccination , Hepatitis B/prevention & control , Hepatitis B Antibodies
9.
Chinese Journal of Neurology ; (12): 1009-1017, 2023.
Article in Chinese | WPRIM | ID: wpr-994926

ABSTRACT

Objective:To comprehensively evaluate the ability of common resting state functional magnetic resonance imaging (rs-fMRI) indices to detect abnormal brain activity in childhood absence epilepsy (CAE).Methods:Simultaneous electroencephalography-functional magnetic resonance imaging (fMRI) data of 20 patients with CAE who were treated in the Jinling Hospital, Nanjing University School of Medicine from February 2010 to September 2021 were retrospectively collected. After excluding 2 patients with CAE with greater head movement, 44 fMRI data containing discharges from 18 patients were obtained finally. The generalized spike and slow-wave discharges (GSWD) related fMRI activation mappings were obtained by using the generalized linear model. At the same time, 94 age- and sex-matched healthy controls underwent rs-fMRI scanning. Meanwhile, 12 indices of rs-fMRI were calculated respectively [amplitude of low frequency fluctuation (ALFF), fractional amplitude of low frequency fluctuation (fALFF), regional homogeneity (ReHo), functional connectivity density (FCD), long FCD, local FCD, granger causality density (GCD)-in, GCD-out, GCD-int, resting state functional magnetic resonance imaging lag analysis (RSLA), Hurst index and brain entropy]. Two-sample t-tests were employed to detect significant differences in 12 indices of rs-fMRI. The Dice coefficient was used to evaluate the overlap between different brain maps of 12 indices of rs-fMRI and the GSWD-related blood oxygenation level dependent (BOLD) activation. Results:Positive activation of GSWD-related BOLD in CAE was mainly in the bilateral thalamus, and negative activation was mainly in default mode network (DMN) related brain regions. There was a significant overlap between the abnormal brain regions detected by various resting-state indicators: compared with normal controls, ALFF, fALFF, ReHo, GCD-in, GCD-out and local FCD were elevated in the bilateral thalamus, while FCD, long FCD, GCD-int and RSLA were decreased in CAE; ALFF, fALFF, ReHo, local FCD, GCD-out, RSLA and brain entropy were decreased in the DMN, while FCD, long FCD, GCD-in and GCD-int were increased in CAE. The Dice coefficient of long FCD was the highest (0.365),FCD was 0.362, while the Hurst index showed the lowest (0.142).Conclusions:Rs-fMRI indices variously revealed abnormal brain activity in CAE, in which the FCD is better for detection of epileptic activity. Rs-fMRI could be helpful to understand the pathophysiological mechanism of CAE, and to find reliable imaging markers.

10.
Chinese Journal of Orthopaedics ; (12): 23-30, 2023.
Article in Chinese | WPRIM | ID: wpr-993406

ABSTRACT

Objective:To evaluate the accuracy of the domestic "Skywalker" surgical robot in implementing personalized lower limb alignment reconstruction scheme in total knee arthroplasty (TKA) and the short-term clinical outcome of robotic assisted TKA.Methods:From September 2020 to January 2021, the data of patients who received surgical robot assisted TKA in 5 clinical centers in China (Shanghai Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Southwest Hospital affiliated to Third Military Medical University, The Affiliated Hospital of Qingdao University, The First Affiliated Hospital of Chongqing Medical University and Yantai Yuhuangding Hospital, and Shanghai Ninth People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine was the group leader) were prospectively collected and retrospectively analyzed. There were 24 males and 82 females with an average age of 67.6±7.3 years, (range 45-80 years); Average body mass index 26.42±4.31 kg/m 2, all the operation were performed by "Skywalker" surgical robot system according to preoperative design based on CT. The operation time, intraoperative blood loss, hospitalization days and postoperative complications were recorded, and the imaging indexes including hip-knee-ankle (HKA), lateral distal angle of femur (LDFA) and medial proximal angle of tibia (MPTA) measured before and after the operation, implant model indexes (preoperative planning implant model and postoperative implant model) and short-term clinical efficacy indexes [Western Ontario and McMaster Universities (WOMAC) osteoarthritis index] pain score, stiffness score, joint function score, total score and SF-12 score before and 3 months after the operation) were compared. Results:The average follow-up period was 109.60±9.80 d, (range 95-143 d). The average operation time of 106 patients was 105.30±23.22 min; The average intraoperative blood loss was 141.70±58.33 ml; The average length of hospitalization was 5.82±2.80 d. One patient had ischemic stroke after operation, and one patient had abnormal liver function after operation. According to the judgment of the investigator, all of them were not related to the operation. The actual angle error is the difference between the preoperative planning angle and the postoperative measurement angle. The absolute error of 99.1% (105/106) of the HKA angle was within 3°, 90.8% (69/76) of LDFA, 98.7% (75/76) of the MPTA. In 45 patients in one center where data were available, the actual implant models used in all patients were consistent with the preoperative planning size, and there were only differences in version selection such as Asian condyle. WOMAC pain score, joint function score, total score was improved from 7.34±2.85, 25.10±9.85, 34.75±13.02 to 3.34±2.66, 14.68±9.64, 18.66±13.49 before and after operation, respectively, which were statistically significant ( P<0.001) and SF-12 physiological score and psychological score were improved form 27.24±6.42, 30.68±8.26 to 38.83±5.74, 39.36±7.85 before and after operation, respectively, which were statistically significant ( t=7.33, P<0.001; t=4.53, P=0.043). Conclusion:Domestic surgical robot system "Skywalker" can assist the surgeon to achieve accurate and personalized reconstruction of lower limb alignment and achieve satisfactory short-term clinical outcomes. The long-term clinical outcomes of personalized reconstruction and survival rate of implant still need to be further studied.

11.
Chinese Pharmacological Bulletin ; (12): 622-626, 2023.
Article in Chinese | WPRIM | ID: wpr-1013806

ABSTRACT

Coronavirus disease-19 (COVID-19), a global epidemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), lead to lung injury in millions of people. SARS-CoV-2 can not only cause cytokine storm, acute respiratory distress syndrome and respiratory failure in the phase of acute infection, but also have potential long-term effects on the lungs. Survivors of severe COVID-19 may develop pulmonary fibrosis, resulting in permanent lung injury. In this review we expound the occurrence and development of COVID-19-related pulmonary fibrosis, summarize the key roles of TGF-p/Smad, TGF-fV MAPK, JAK/STAT, Wnt/(3-catenin, YAP/TAZ, NF-KB and PI3K/Akt signal pathways in this process, and analyze the advantages and disadvantages of antiviral drugs, anti-fibrosis drugs, cytokine-targeted drugs, corticosteroids, spironolactone, traditional Chinese medicine prescriptions and lung transplantation in its treatment. This review may provide a reference for the study of pathological mechanism and clinical treatment of COVID-19-re-lated pulmonary fibrosis.

12.
JOURNAL OF RARE DISEASES ; (4): 427-431, 2023.
Article in English | WPRIM | ID: wpr-1004970

ABSTRACT

Glucagonoma is a rare neuroendocrine tumor of α cells of the pancreas. The tumor excessively secretes glucagon and causes glucagonoma syndrome.70%-90% of patients with glucagonoma will develop necrolytic migratory erythema (NME). We reported a patient of glucagonoma syndrome who was presented to the dermatology outpatient clinic with a 2-year-history of recurrent erythema and scaling on the skin migrating throughout the body. A skin biopsy was performed and resulting features matched with NME, whilst imaging examinations suggested a soft tissue density tumor present in the tail of the pancreas with somatostatin receptor expression and laboratory tests found an elevated levels of serum glucagon. After the diagnosis was confirmed, the patient was treated with surgical resection of the glucagonoma and the skin eruptions resolved rapidly in 4 days. Meanwhile, we reviewed relevant literature published in recent years and summarized its clinical characteristics in order to improve its understanding by clinicians, including clinical manifestations, laboratory and imaging examinations, diagnosis and treatments.

13.
Chinese Journal of Preventive Medicine ; (12): 103-107, 2022.
Article in Chinese | WPRIM | ID: wpr-929575

ABSTRACT

Influenza is an infectious respiratory disease caused by the influenza viruses. Older people, infants and people with underlying medical conditions could have a higher risk of severe influenza symptoms and complications. The co-infection of Coronavirus Diseases 2019 (COVID-19) with influenza viruses could lead to the complication of prevention, diagnosis, control, treatment, and recovery of COVID-19. Influenza vaccine and COVID-19 vaccine overlapped in target populations, vaccination time, and inoculation units. Although there was insufficient evidence on the immunogenicity and safety of co-administration of influenza vaccine and COVID-19 vaccine, World Health Organization and some countries recommended co-administration of inactivated influenza vaccine and COVID-19 vaccine. This review summarized domestic and international vaccination policies and research progress, and put forward corresponding suggestions in order to provide scientific support for the formulation of vaccination strategy on seasonal influenza vaccine and COVID-19 vaccine.


Subject(s)
Aged , Humans , Infant , COVID-19 , COVID-19 Vaccines , China , Influenza Vaccines , Influenza, Human/prevention & control , Pandemics/prevention & control , SARS-CoV-2 , Seasons , Vaccination
14.
Acta Pharmaceutica Sinica B ; (6): 262-273, 2022.
Article in English | WPRIM | ID: wpr-929292

ABSTRACT

Gastrointestinal mucositis is one of the most debilitating side effects of the chemotherapeutic agent irinotecan (CPT-11). Andrographolide, a natural bicyclic diterpenoid lactone, has been reported to possess anti-colitis activity. In this study, andrographolide treatment was found to significantly relieve CPT-11-induced colitis in tumor-bearing mice without decreasing the tumor suppression effect of CPT-11. CPT-11 causes DNA damage and the release of double-stranded DNA (dsDNA) from the intestine, leading to cyclic-GMP-AMP synthase (cGAS)‒stimulator of interferon genes (STING)-mediated colitis, which was significantly decreased by andrographolide both in vivo and in vitro. Mechanistic studies revealed that andrographolide could promote homologous recombination (HR) repair and downregulate dsDNA‒cGAS‒STING signaling and contribute to the improvement of CPT-11-induced gastrointestinal mucositis. These results suggest that andrographolide may be a novel agent to relieve gastrointestinal mucositis caused by CPT-11.

15.
Acta Pharmaceutica Sinica B ; (6): 149-166, 2022.
Article in English | WPRIM | ID: wpr-929285

ABSTRACT

Colorectal cancer (CRC), a malignant tumor worldwide consists of microsatellite instability (MSI) and stable (MSS) phenotypes. Although SHP2 is a hopeful target for cancer therapy, its relationship with innate immunosuppression remains elusive. To address that, single-cell RNA sequencing was performed to explore the role of SHP2 in all cell types of tumor microenvironment (TME) from murine MC38 xenografts. Intratumoral cells were found to be functionally heterogeneous and responded significantly to SHP099, a SHP2 allosteric inhibitor. The malignant evolution of tumor cells was remarkably arrested by SHP099. Mechanistically, STING-TBK1-IRF3-mediated type I interferon signaling was highly activated by SHP099 in infiltrated myeloid cells. Notably, CRC patients with MSS phenotype exhibited greater macrophage infiltration and more potent SHP2 phosphorylation in CD68+ macrophages than MSI-high phenotypes, suggesting the potential role of macrophagic SHP2 in TME. Collectively, our data reveals a mechanism of innate immunosuppression mediated by SHP2, suggesting that SHP2 is a promising target for colon cancer immunotherapy.

16.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 133-140, 2022.
Article in Chinese | WPRIM | ID: wpr-940494

ABSTRACT

ObjectiveTo screen the appropriate reference genes for real-time fluorescence-based quantitative polymerase chain reaction(Real-time PCR)analysis of the Andrographis paniculata under methyl jasmonate(MeJA)and various abiotic stresses. MethodThe actin 1(ACT1),actin 2(ACT2),elongation factor(EF-1α),glyceraldehyde-3-phosphate dehydrogenase(GAPDH),tubulin(TUB),polyubiquitin(UBQ), and 18S rRNA(18S)gene were selected as candidate reference genes based on the RNA-seq data of high temperature,drought, UV, and MeJA. The expression of seven candidate reference genes in the A. paniculata leaves was assessed by Real-time PCR,and the stability was analyzed by geNorm,NormFinder,BestKeeper, and Refinder. ResultThe results of stability evaluated by geNorm,NormFinder, and BestKeeper were not the same due to different indicators. As analyzed by Refinder, for the stability of the expression, the genes were ranked as UBQ>18S>EF-1α>ACT2>ACT1>GAPDH>TUB under high temperature stress, ACT1>UBQ>EF-1α>18S>ACT2>GAPDH>TUB under drought stress, EF-1α>TUB>ACT2>UBQ>18S>GAPDH>ACT1 under UV stress, and ACT1>EF-1α>UBQ>ACT2>18S>TUB>GAPDH under MeJA stress. Among them,18S gene was not suitable as an internal reference gene duo to its high expressive abundance. This study also verified the relative expression level of andrographolide synthesis-related gene hydroxy-methylglutaryl-CoA synthase (HMGS) in the four stresses on the basis of transcriptome data,and found that the Real-time PCR results of appropriate internal reference genes were accurate and reliable. ConclusionUBQ-ACT1-UBQ,EF-1α-TUB,and ACT1-EF-1α were the suitable combinations under stresses of high temperature,drought,UV, and MeJA. This study is expected to provide references for the research on function regulation and expression of genes in A. paniculata under high temperature,drought,UV, and MeJA stresses.

17.
Chinese Journal of Microbiology and Immunology ; (12): 456-463, 2022.
Article in Chinese | WPRIM | ID: wpr-958211

ABSTRACT

Sequential immunization is one of the special means to solve the shortage of vaccines, respond to SARS-CoV-2 variants and improve the efficacy of vaccines in the current pandemic period. This article mainly reviewed five sequential immunization strategies using the vaccines authorized by World Health Organization: priming with inactivated vaccine and boosting with recombinant protein vaccine, vector vaccine or mRNA vaccine; priming with vector vaccine and boosting with mRNA vaccine; prime-boost immunization with mRNA vaccines produced by different manufactures. Results of the related studies showed that heterologous sequential immunization strategies were safe and effective, and higher immunogenicity and efficacy could be achieved by sequential immunization. In addition, sequential immunization could provide certain protective effects against SARS-CoV-2 variants.

18.
Chinese Journal of Biochemistry and Molecular Biology ; (12): 789-798, 2022.
Article in Chinese | WPRIM | ID: wpr-1015694

ABSTRACT

Adipocyte enhancer binding protein 2, as a component protein of Polycomb repressive complex (PRC2), is involved in the proliferation and migration of many tumor cells. However, its role in HCC is still unclear. In this study, we identify that AEBP2 was upregulated in HCC samples from the UALCAN and Kaplan-Meier Plotter database, which was correlated to the overall survival time of HCC patients. Real-time quantitative PCR and Western blotting confirmed that the expression of AEBP2 in HCC cells was higher than normal liver cells. After silencing AEBP2 in HepG2 and Huh-7 cells, the effects of the proliferation, apoptosis, migration and invasion were detected by colony formation, CCK-8, flow cytometry, scratch healing and Transwell chamber, respectively. Compared with the control group, down-regulation of AEBP2 expression inhibited the proliferation, migration and invasion in HepG2 and Huh-7 cells, as well as promoted apoptosis (P<0. 05). Immunofluorescence and Western blotting results showed that AEBP2 silencing inhibited epithelial-mesenchymal transformation (EMT) (P < 0. 05). Bioinformatics analysis showed that AEBP2 is involved the PI3K/Akt signaling pathway. Western blotting results confirmed that silencing AEBP2 down-regulated the expression levels of PI3K, p-AKT (S473), mTOR, MMP-2 and MMP-9 proteins (P<0. 05). In addition, the effects of AEBP2 silencing on HepG2 cells migration and invasion could be reversed by PI3K/Akt pathway agonist insulin-like Growth Factors (IGF-1) (P < 0. 01). In summary, our study showed that AEBP2 promoted the proliferation and migration of HCC cell by regulating PI3K/AKT pathway. This study provided a theoretical basis for the role of AEBP2 in HCC.

19.
Chinese Pharmacological Bulletin ; (12): 1627-1633, 2022.
Article in Chinese | WPRIM | ID: wpr-1013982

ABSTRACT

Aim To explore the characteristics and mechanism of resveratrol(Res)in promoting apoptosisof T lymphocytes and to investigate the therapeutic effect of Res on experimental autoimmune encephalomyelitis(EAE)in mice. Methods Annexin V/PI double staining was used to investigate the effect of Res on the apoptosis of mouse primary naïve T lymphocytes and anti-CD3/anti-CD28 activated T lymphocytes. Activation-induced cell death models were established on CD4+ T lymphocytes and Jurkat cells in vitro,and the effect of Res on activation-induced cell death was detected by PI single staining or Annexin V/PI double staining. The expression of apoptosis related proteins were detected by Western blot. EAE model in mice was induced by MOG35-55,and the therapeutic effect of Res administration was investigated. The apoptosis of CD4+ T lymphocytes from vehicle group and Res group was detected. Results Res did not affect the survival of naïve T cells,but promoted the apoptosis of activated T lymphocytes. With the increase of Res concentration,activation-induced cell death of CD4+ T cells and Jurkat cells significantly increased,and the cleavage of apoptosis related proteins PARP and Caspase-3 increased. In addition,Res delayed the onset of EAE,reduced the clinical score,and decreased the infiltration of inflammatory cells in spinal cord. The CD4+ T lymphocytes from the mice with Res administration were more sensitive to activation-induced cell death. Conclusion Res promotes activation-induced cell death of T lymphocytes and ameliorates EAE in mice.

20.
JOURNAL OF RARE DISEASES ; (4): 289-295, 2022.
Article in English | WPRIM | ID: wpr-1005017

ABSTRACT

A 15-year-old female was referred to the hospital with intermittent fever, where multiple systemic abnormalities were found, such as splenomegaly, secondary hypersplenism, retinitis pigmentosa, and ectodermal dysplasia. Medical history revealed that she had suffered recurrent respiratory infections, blurred vision at night, and dysplasia of teeth and nail beds since childhood. Then she was suspected to be experiencing ROSAH syndrome, a rare disease newly recognized in recent years, which was finally confirmed by gene sequencing results. During a course of treatment with tumor necrosis factor inhibitors, recurrent fever with elevated inflammatory markers reappeared, and the child developed headaches. To guide the comprehensive treatment and improve the patient's quality of life, the multidisciplinary team in Peking Union Medical College Hospital discussed together and directed the following treatment.

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