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1.
Article in Chinese | WPRIM | ID: wpr-935753

ABSTRACT

Objective: To explore the role and significance of pyroptosis in gas explosion-induced acute lung injury (ALI) in rats. Methods: In February 2018, 126 SPF male SD rats were selected and randomly divided into blank control group (18 rats) and experimental group (40 m, 80 m, 120 m, 160 m, 200 m and 240 m, 18 per group) . The experimental group carried out gas explosion in the roadway to build the ALI model, the control group did not carry out gas explosion, and other conditions were consistent with the experimental group. Respiratory function indexes such as respiratory frequency (f) , tidal volume (TV) , minute ventilation (MV) and airway stenosis index (Penh) were measured 24 hours after the explosion. 5 rats in each group were sacrificed after anesthesia, Hematoxylin-Eosin (HE) staining was used to observe the pathological morphology of lung tissue. Immunohistochemistry was used to detect the content of Caspase-1. Western blotting was used to detect the content of cell pyroptosis including nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) , Caspase-1, interleukin-1β (IL-1β) and interleukin-18 (IL-18) in lung tissue related protein expression. Results: The f and MV of rats in the experimental group were higher than those in the control group (P<0.05) . Except for the 40 m and 80 m groups, the TV of rats in the other experimental groups were higher than those in the control group (P<0.05) . Except for the 40 m group, the Penh of rats in the experimental groups were lower than those in the control group (P<0.05) . HE staining showed that the lung tissue of the experimental groups at different distance points showed obvious edema of the pulmonary interstitium and alveoli, a large number of red blood cells and inflammatory cells exuded in the alveolar space, thickening of the pulmonary interstitium, and increased lung injury score (P<0.05) . The results of immunohistochemistry showed that the positive expression of Caspase-1 in each experimental group was higher than that in the control group (P<0.05) . Western blotting results showed that the expression of pyroptosis-related proteins in each experimental group was higher than that in the control group (P<0.05) . Conclusion: Pyroptosis is involved in the pathophysiological process of gas explosion-induced ALI in rats.


Subject(s)
Acute Lung Injury/pathology , Animals , Explosions , Lung/pathology , Male , Pyroptosis , Rats , Rats, Sprague-Dawley
2.
Chinese Journal of Urology ; (12): 368-373, 2022.
Article in Chinese | WPRIM | ID: wpr-933234

ABSTRACT

Objective:To evaluate the efficacy and side effects of PD-1 monoclonal antibody in the treatment of advanced metastatic renal cell carcinoma in China.Methods:The clinical data of 117 patients with advanced metastatic renal cell carcinoma (mRCC) treated with PD-1 monoclonal antibody from October 2016 to February 2022 were retrospectively analyzed. There were 87 males (74.4%) and 30 females (25.6%), with an average age of (57.9±10.9) years old, BMI of (23.6±3.4) kg/m 2and smoking history of 79 (67.5%). There were 44 cases (37.6%) with hypertension, 19 (16.2%) cases of diabetes. The ECOG score of 59.8% (70/117) patients was 0, 33.3% (39/117) was 1, 4.3% (5/117) was 2, and 2.5% (3/117) was 3. The pathological type of 104 cases were renal clear cell carcinoma (ccRCC), 8 cases of papillary renal cell carcinoma, 2 cases of chromophobe cell carcinoma, 2 cases of collecting duct carcinoma and 1 case of eosinophilic cell carcinoma. The general condition of the overall population and the overall survival (OS) of relevant subgroups were analyzed. Secondary goals included progression free survival (PFS), objective response rate (ORR), adverse reactions, overall survival (OS), and progression free survival (PFS). Results:65.8% (77 / 117) of the patients chose targeted combined with PD-1 monoclonal antibody in the first-line treatment. The main targeted drugs were acitinib (81.8%, 63 / 77), tirelizumab (37.6%, 29 / 77) and cindilimab (25.9%, 20 / 77). After first-line treatment, 19.6.1% (23 / 117) patients needed to be converted to second-line treatment, and 15 patients changed the type of PD-1 antibody during treatment. In addition, the targeted drug of combined therapy was replaced by acitinib in 8 patients. The main causes of drug withdrawal were disease progression (70.7%, 29 / 41) and death (29.2%, 12 / 41). The median OS of the overall population was 35.6 (19-60) months and PFS was 12.1 (1-60) months. The ORR of the overall population was 47.8% (56 / 117). 4.2% (5/117) patients had complete remission, another 17.0% (20/117) patients were in stable condition, and 43.5% (51 / 117) patients were in partial remission. In the first-line treatment, the median PFS time of targeted combined with PD-1 monoclonal antibody was 12.6 (1-30) months, the median PFS time of PD-1 single drug immunotherapy was 10.5 (1-60) months. In the second-line treatment, the PFS of patients treated with PD-1 monoclonal antibody was 10.1 (4-19) months, and that of patients treated with PD-1 monoclonal antibody combined with targeted therapy was 11.7 (1-25) months. The most common adverse reactions were elevated blood pressure (18.5%, 23 / 124), followed by hypothyroidism (15.3%%, 19/124), rash (14.5%, 18 / 124), elevated transaminase (10.5%, 13 / 124) and bone marrow suppression (9.7%, 12/124). 9.4% (11 / 117) patients needed to reduce the related adverse reactions by interrupting the treatment control of PD-1 monoclonal antibody.Conclusions:The safety and efficacy of PD-1 monoclonal antibody in domestic patients are better, and the side effects are less. The efficacy and safety of PD-1 monoclonal antibody combined with targeted therapy in the real world population are consistent with many key clinical trials abroad. PD-1 monoclonal antibody combined with targeted drugs can be popularized in the domestic MRCC population.

3.
Acta Pharmaceutica Sinica ; (12): 2612-2621, 2022.
Article in Chinese | WPRIM | ID: wpr-941520

ABSTRACT

More and more studies have shown that NOD-like receptor protein 3 (NLRP3) inflammasome has become the regulatory factor of inflammatory response and protective immunity, and the assembly and activation of NLRP3 inflammasomes are closely related to the anti-tumor immunity effect. Depending on the cell type and stimuli, activation of the NLRP3 inflammasome can induce immune cells to become polarized, hyperactive, or pyroptotic, releasing interleukin (IL)-1β and IL-18, which leads to cascade immune or inflammatory responses, and its role in tumor immunity has received extensive attention. Here, we review the mechanisms of the NLRP3 inflammasome enhancing CD8+ T cells-mediated anti-tumor immunity by inducing the pyroptosis of tumor cell, the pyroptosis or hyperactive state of dendritic cells (DCs), and the pyroptosis or polarization of the macrophages. Different anti-tumor immune roles of NLRP3 inflammasome activation in tumor cells and immune cells provide new directions for future research and may influence the development of next-generation immunotherapy.

4.
Article in Chinese | WPRIM | ID: wpr-939644

ABSTRACT

OBJECTIVES@#To establish a nomogram model for predicting the risk of death of very preterm infants during hospitalization.@*METHODS@#A retrospective analysis was performed on the medical data of 1 714 very preterm infants who were admitted to the Department of Neonatology, the Third Affiliated Hospital of Zhengzhou University, from January 2015 to December 2019. These infants were randomly divided into a training cohort (1 179 infants) and a validation cohort (535 infants) at a ratio of 7∶3. The logistic regression analysis was used to screen out independent predictive factors and establish a nomogram model, and the feasibility of the nomogram model was assessed by the validation set. The area under the receiver operating characteristic curve (AUC), calibration curve, and decision curve analysis (DCA) were used to assess the discriminatory ability, accuracy, and clinical applicability of the model.@*RESULTS@#Among the 1 714 very preterm infants, 260 died and 1 454 survived during hospitalization. By the multivariate logistic regression analysis of the training set, 8 variables including gestational age <28 weeks, birth weight <1 000 g, severe asphyxia, severe intraventricular hemorrhage (IVH), grade III-IV respiratory distress syndrome (RDS), and sepsis, cesarean section, and use of prenatal glucocorticoids were selected and a nomogram model for predicting the risk of death during hospitalization was established. In the training cohort, the nomogram model had an AUC of 0.790 (95%CI: 0.751-0.828) in predicting the death of very preterm infants during hospitalization, while in the validation cohort, it had an AUC of 0.808 (95%CI: 0.754-0.861). The Hosmer-Lemeshow goodness-of-fit test showed a good fit (P>0.05). DCA results showed a high net benefit of clinical intervention in very preterm infants when the threshold probability was 10%-60% for the training cohort and 10%-70% for the validation cohort.@*CONCLUSIONS@#A nomogram model for predicting the risk of death during hospitalization has been established and validated in very preterm infants, which can help clinicians predict the probability of death during hospitalization in these infants.


Subject(s)
Cesarean Section , Female , Fetal Growth Retardation , Hospitalization , Humans , Infant , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases , Nomograms , Pregnancy , Retrospective Studies
5.
Neuroscience Bulletin ; (6): 263-274, 2022.
Article in English | WPRIM | ID: wpr-929087

ABSTRACT

Protein O-GlcNAcylation is a post-translational modification that links environmental stimuli with changes in intracellular signal pathways, and its disturbance has been found in neurodegenerative diseases and metabolic disorders. However, its role in the mesolimbic dopamine (DA) system, especially in the ventral tegmental area (VTA), needs to be elucidated. Here, we found that injection of Thiamet G, an O-GlcNAcase (OGA) inhibitor, in the VTA and nucleus accumbens (NAc) of mice, facilitated neuronal O-GlcNAcylation and decreased the operant response to sucrose as well as the latency to fall in rotarod test. Mice with DAergic neuron-specific knockout of O-GlcNAc transferase (OGT) displayed severe metabolic abnormalities and died within 4-8 weeks after birth. Furthermore, mice specifically overexpressing OGT in DAergic neurons in the VTA had learning defects in the operant response to sucrose, and impaired motor learning in the rotarod test. Instead, overexpression of OGT in GABAergic neurons in the VTA had no effect on these behaviors. These results suggest that protein O-GlcNAcylation of DAergic neurons in the VTA plays an important role in regulating the response to natural reward and motor learning in mice.


Subject(s)
Animals , Dopaminergic Neurons/physiology , GABAergic Neurons/physiology , Mice , Nucleus Accumbens/metabolism , Reward , Ventral Tegmental Area/metabolism
6.
Article in Chinese | WPRIM | ID: wpr-908961

ABSTRACT

Objective:To study the influence of objective structured clinical examination (OSCE) assessment mode on learning interest and critical thinking of nursing students in operating room.Methods:There were 49 operating room nursing students from April 2019 to April 2020 who were selected as the observation group, receiving the teaching and assessment mode of OSCE. In addition, 49 operating room nursing students from March 2018 to March 2019 were included as the control group, receiving the conventional teaching and assessment mode. The nursing students' learning attitude scale was used to compare the learning interest of the two groups, and the critical thinking level of nursing students was recorded by Chinese critical thinking disposition inventory-Chinese version (CTDI-CV). SPSS 24.0 software was used to analyze the data with t test and chi-square test. Results:There were statistically significant differences in the scores of learning interest, learning experience, learning habits, professional cognition and the total scores of the learning attitude of nursing students after the assessment between the observation group and the control group ( t=4.861, t=4.885, t=3.466, t=4.206, t=8.292; all P<0.05). There were statistically significance of curiosity, truth seeking, open thinking, analytical ability, systematic ability, self-confidence in thinking, cognitive maturity and the CTDI-CV total scores after the assessment between the observation group and the control group ( t=4.262, t=4.311, t=2.754, t=4.854, t=3.984, t=2.864, t=4.267, t=2.729; P<0.05). Conclusion:The OSCE assessment mode used in operating room for nursing students is helpful to improve the learning interest and the cultivation of students' critical thinking.

7.
Article in Chinese | WPRIM | ID: wpr-906474

ABSTRACT

Oral nanoparticles (NPs) has gradually become a approach to improve oral bioavailability of biopharmaceutics classification system (BCS) Ⅱ, Ⅲ, Ⅳ drugs, and the transmembrane transport mechanism in the gastrointestinal tract largely depends on physicochemical characteristics of NPs. It would be beneficial to design the NPs with high transport efficiency and effectively improve the oral bioavailability of drugs by adopting a reasonable research model to analyze the transmembrane mechanism of the oral NPs and exactly reveal the relationship between the physicochemical properties and the transport mechanism of NPs. This review focused on summarizing the transmembrane approaches of oral NPs, comparing the advantages and disadvantages of the common cell models, concluding the potential interaction between the physicochemical properties and transmembrane process of NPs, and proposing the research strategy of transport mechanism based on in situ intestinal perfusion, with the purpose of discovering a suitable research model for studying the transport mechanism of different NPs, providing a basis for regulating the transport performance of the NPs to improve the oral bioavailability, and expanding the application of oral NPs in the development of new drugs.

8.
Article in Chinese | WPRIM | ID: wpr-906025

ABSTRACT

Objective:To explore the clinical efficacy of modified Ditantang combined with acupuncture in the treatment of dysphagia after apoplexy (DAS) syndrome of phlegm and blood stasis blocking collaterals. Method:One hundred and eight patients were randomly divided into control group (54 cases) and observation group (54 cases) by number table. Both groups underwent nutritional management,rehabilitation training and acupuncture. Patients in control group additionally took Tongluo Huatan capsules, 3 granules/time, 3 times/day, while patients in observation received modified Ditantang. Both groups had two weeks of treatment. The Kubota's drinking water test, swallowing contrast examination (VFSS), and standard swallowing function assessment (SSA) were conducted. Swallowing disorder specific quality of life scale (SWAL-QOL) and sputum collateral stasis syndrome were scored before and after treatment. The levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) and neuron-specific enolase (NSE) before and after treatment. The occurrence of pneumonia, malnutrition, dehydration and aspiration were then recorded. Result:The clinical effective rate was (47/49) 95.92%in the observation group, higher than (41/50) 82.00% in the control group's (<italic>χ</italic><sup>2</sup>=4.854,<italic>P</italic><0.05). The grade of Kubota's drinking water test in observation group was lower than that in the control group(<italic>Z</italic>=2.211,<italic>P</italic><0.05). VFSS swallowing dysfunction in observation group was lighter than that in control group(Z=1.969,<italic>P</italic><0.05). The scores of Kubota's drinking water test, SSA and phlegm and blood stasis blocking collateral syndrome in the observation group were all lower than those in the control group(<italic>P</italic><0.01), while the VFSS score was higher than that in control group (<italic>P</italic><0.01). The swallowing symptom score, other symptom scores and total SWAL-QOL scores of the observation group were higher than those of the control group(<italic>P</italic><0.01). The levels of BDNF and NGF in the observation group were higher than those in the control group (<italic>P</italic><0.01), but the NSE level was lower than that in the control group(<italic>P</italic><0.01). The complication rate in the observation group was (6/49)12.24%, which was lower than (15/50)30.00% in the control group(<italic>χ</italic><sup>2</sup>=4.668,<italic>P</italic><0.05). Conclusion:On the basis of nutrition management and rehabilitation training, modified Ditantang combined with acupuncture can reduce the risk of dysphagia and aspiration, improve the degree of neurological deficits, improve the quality of life, and reduce complications in treatment of DAS syndrome of phlegm and blood stasis, with significant clinical efficacy.

9.
Article in Chinese | WPRIM | ID: wpr-888145

ABSTRACT

Twenty batches of Aurantii Fructus Immaturus(AFI) were collected, with their peel and pulp taken as research objects. Ultra-high performance liquid chromatography(UPLC) fingerprints of peel and pulp of AFI were established with 17 common peaks in peel and 10 in pulp. Six kinds of flavonoids were identified, i.e., narirutin, naringin, rhoifolin, hesperidin, neohesperidin and nobiletin. The Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine was employed for similarity analysis, which showed that the chromatographic peaks of peel and pulp were basically similar to their respective reference fingerprints, with all similarities greater than 0.90. The similarity between peel and pulp of the same batch of AFI ranged from 0.850 to 0.983. Cluster analysis(CA), principal component analysis(PCA), and orthogonal partial least squares discriminant analysis(OPLS-DA) were conducted on the common peaks of peel and pulp of AFI with SPSS 17.0 and SIMCA 14.1. Combined with the reference fingerprints, these analyses revealed 12 differential components regarding peel and pulp. Further, the content of the 6 flavonoids and synephrine was determined. The proposed method integrating UPLC fingerprint and multicomponent quantitative analysis is applicable to the quality evaluation of AFI. The results provide a certain basis for the scientific connotation about the appearance characteristic of AFI.


Subject(s)
Chromatography, High Pressure Liquid , Citrus , Drugs, Chinese Herbal , Synephrine
10.
Article in Chinese | WPRIM | ID: wpr-887899

ABSTRACT

Objective To investigate the oral health status and awareness of urban children in Lhasa,aiming to provide a data basis for the prevention and treatment of children's caries and the promotion of oral health education. Methods A total of 504 Tibetan students were selected by cluster sampling from 2 primary schools in Chengguan District of Lhasa.All the participants were required to take oral health examination and complete a questionnaire about oral health awareness and behavior. Results The caries prevalence rate and mean decayed-missing-filled tooth(DMFT)of permanent teeth were 75.00% and 2.18±1.91,respectively.The rates of pit and fissure sealant and filling of permanent teeth were 3.77% and 6.81%,respectively.The caries prevalence rate of first permanent molars was 47.62%.The mean DMFT of permanent teeth and caries prevalence rate of first permanent molar were significantly higher in female group(


Subject(s)
Child , DMF Index , Dental Caries/epidemiology , Female , Humans , Oral Health , Oral Hygiene , Prevalence , Schools , Students , Surveys and Questionnaires
11.
Article in Chinese | WPRIM | ID: wpr-879896

ABSTRACT

OBJECTIVE@#To study the clinical features of very preterm infants with prelabor rupture of membranes (PROM) and predictive factors for early-onset sepsis (EOS) and death.@*METHODS@#A retrospective analysis was performed for the clinical data of the very preterm infants with PROM (with a gestational age of < 32 weeks) who were admitted to the neonatal intensive care unit from January 2018 to May 2020. According to the time from membrane rupture to delivery, the infants were divided into four groups: < 18 hours (@*RESULTS@#There was no significant difference in the incidence rates of major neonatal complications and mortality rate among the very preterm infants with different times of PROM (@*CONCLUSIONS@#Prolonged PROM does not increase the incidence of neonatal complications and mortality in very preterm infants. Adverse outcomes of very preterm infants with PROM are mainly associated with lower birth weights, lung immaturity, and systemic infection.


Subject(s)
Female , Fetal Membranes, Premature Rupture , Gestational Age , Humans , Infant , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases , Infant, Very Low Birth Weight , Pregnancy , Retrospective Studies
12.
Acta Pharmaceutica Sinica ; (12): 319-327, 2021.
Article in Chinese | WPRIM | ID: wpr-872598

ABSTRACT

Chalcone isomerase (CHI) is the second rate-limiting enzyme involved in the biosynthetic pathway of flavonoids in Glycyrrhiza uralensis. Based on our previous studies, we selected the specific CHI haplotype (GenBank Accession No. KY115232) to maximize flavonoid accumulation. We constructed a plant binary expression vector for overexpression of this CHI gene by the gene fusion method and transfected the plasmid into Agrobacterium tumefaciens ACCC10060 by electroporation. The recombinant A. tumefaciens ACCC10060 subsequently was used to infect cotyledons and hypocotyls of G. uralensis to obtain transgenic hairy roots. A qRT-PCR method was used to determine the copy number of CHI and a UPLC method was used to assay the content of four flavonoids in different hairy root lines. The qRT-PCR results showed that the copy number of CHI in hairy roots was 1 or 5. UPLC results showed that the content of total flavonoids, liquiritin, liquiritigenin, and isoliquiritigenin in transgenic hairy root samples was significantly higher than that in wild-type samples. This study demonstrates that overexpression of CHI significantly increases the content of flavonoids in hairy roots of G. uralensis. This work provides a theoretical basis for clarifying the function of CHI. Three transgenic hairy root lines of G. uralensis were isolated which can be used to increase the accumulation of licorice flavonoids in vitro.

13.
Chinese Journal of Urology ; (12): 491-496, 2021.
Article in Chinese | WPRIM | ID: wpr-911056

ABSTRACT

Objective:To investigate the experience and results of the modified lateral prostate capsule sparing robot-assisted radical cystectomy-orthotopic ileal neobladder (LPCS-RARC-OIN).Methods:From December 2018 to November 2020, 19 patients received LPCS-RARC-OIN by a single surgeon in Sun Yat-sen Memorial Hospital, Sun Yat-sen University. LPCS-RARC-OIN was performed on male patients with high-risk non-muscle-invasive bladder cancer or muscle-invasive bladder cancer cT 2N 0M 0 without tumour in the bladder neck or urethra, and prostate cancer was ruled out by MRI and serum PSA<2.5ng/ml. The average age was 57.6 years, the average IIEF-5 score was 20.4. Separating the prostatic adenoma and the lateral prostate capsule from the base to the apex of the prostate, and retaining the lateral prostate surgical capsule or lateral prostate capsule about 1-2mm thickness. Patients were followed up and urinary function, sexual function and oncological outcomes were recorded. Results:All 19 operations were finished successfully. The average operation time was 279.9 (225-345) min and average estimated blood loss was 88.9 (30-200) ml. The average postoperative hospital stays was 15.8 (9 -23) days. The average lymph node yields was 23.3 (11-42). All surgical margins were negative and no incidental prostate cancer was found. 2 weeks, 1 month, 3 months and 6 months after catheter removal, the daytime and nighttime continence were 42.1% (8/19)and 36.8% (7/19), 63.2% (12/19)and 63.2% (12/19), 78.9% (15/19) and 73.7% (14/19), 94.7% (18/19) and 89.5% (17/19), respectively. 3 months and 6 months after operation, the average IIEF-5 score was 7.2 and 10.1 points respectively. The average follow-up was 10.6 months (5.4-26.1 months)and no recurrence or distant metastasis was found in this study.Conclusions:LPCS-RARC-OIN could improve the urinary and sexual function in selected patients. However, the long-term follow up is needed for functional and oncological outcomes.

14.
Neuroscience Bulletin ; (6): 1289-1302, 2021.
Article in English | WPRIM | ID: wpr-922623

ABSTRACT

Growth differentiation factor 15 (GDF-15) is a member of the transforming growth factor-β superfamily. It is widely distributed in the central and peripheral nervous systems. Whether and how GDF-15 modulates nociceptive signaling remains unclear. Behaviorally, we found that peripheral GDF-15 significantly elevated nociceptive response thresholds to mechanical and thermal stimuli in naïve and arthritic rats. Electrophysiologically, we demonstrated that GDF-15 decreased the excitability of small-diameter dorsal root ganglia (DRG) neurons. Furthermore, GDF-15 concentration-dependently suppressed tetrodotoxin-resistant sodium channel Nav1.8 currents, and shifted the steady-state inactivation curves of Nav1.8 in a hyperpolarizing direction. GDF-15 also reduced window currents and slowed down the recovery rate of Nav1.8 channels, suggesting that GDF-15 accelerated inactivation and slowed recovery of the channel. Immunohistochemistry results showed that activin receptor-like kinase-2 (ALK2) was widely expressed in DRG medium- and small-diameter neurons, and some of them were Nav1.8-positive. Blockade of ALK2 prevented the GDF-15-induced inhibition of Nav1.8 currents and nociceptive behaviors. Inhibition of PKA and ERK, but not PKC, blocked the inhibitory effect of GDF-15 on Nav1.8 currents. These results suggest a functional link between GDF-15 and Nav1.8 in DRG neurons via ALK2 receptors and PKA associated with MEK/ERK, which mediate the peripheral analgesia of GDF-15.


Subject(s)
Analgesia , Animals , Ganglia, Spinal , Growth Differentiation Factor 15 , Rats , Sensory Receptor Cells , Sodium Channels , Tetrodotoxin/pharmacology
15.
Article in Chinese | WPRIM | ID: wpr-828487

ABSTRACT

OBJECTIVE@#To provide data support for the study of pathogenic mechanism of SARS-CoV-2 at the molecular level, and provide suitable candidate targets for vaccine, antibody and drug research and development through comparative analysis for structural characteristics and epitopes of S protein of SARS-CoV-2 and SARS-CoV.@*METHODS@#Based on the reference sequences of S protein, physical and chemical properties, hydrophobicity, signal peptide, transmembrane region, domain, secondary structure, tertiary structure analysis and antigenic epitopes prediction were carried out. Meanwhile, the tissue expression, related pathways and reactome pathways of angiotensis Ⅰ converting enzyme 2 (ACE2) and C-type lectin domain family 4 member M (CLEC4M) receptors were analyzed.@*RESULTS@#The amino acid sequence of S protein of SARS-CoV-2 and SARS-CoV has a 75.80% consistency. The structural characteristics of the two coronaviruses are highly consistent, but the secondary structure and tertiary structure of SARS-CoV-2 is not as obvious as SARS-CoV. ACE2 and CLEC4M are expressed in alimentary system, heart, kidney, lung and placenta. The main related the pathways of renin-angiotensin system, protein digestion and absorption pathway, and the reactome pathways of metabolism of angiotensinogen to angiotensins, GPCR ligand binding, are related to typical symptoms of coronavirus disease 2019 induced by SARS-CoV-2. Three pairs of highly or completely homologous epitopes of S protein were obtained. The 600-605, 695-703 and 888-896 amino acid residues in SARS-CoV-2 were highly homologous with 586-591, 677-685 and 870-878 amino acid residues in SARS-CoV, respectively.@*CONCLUSIONS@#The similarity of S protein of SARS-CoV-2 and SARS-CoV determines that they have similar infection patterns and clinical manifestations. The candidate epitopes with high reliability can provide reference for virus diagnosis and vaccine development.


Subject(s)
Betacoronavirus , Cell Adhesion Molecules , Coronavirus Infections , Epitopes , Humans , Lectins, C-Type , Ligands , Pandemics , Peptidyl-Dipeptidase A , Pneumonia, Viral , Receptors, Cell Surface , Receptors, Virus , Reproducibility of Results , Spike Glycoprotein, Coronavirus
16.
Article in English | WPRIM | ID: wpr-793018

ABSTRACT

Objective@#Di-(2-ethylhexyl) phthalate (DEHP) is a ubiquitous environmental contaminant. As an endocrine disruptor, it seriously threatens human health and ecological environmental safety. This study examines the impact of intervention with soybean isoflavones (SIF) on DEHP-induced toxicity using a metabonomics approach.@*Methods@#Rats were randomly divided into control (H), SIF-treated (A, 86 mg/kg body weight), DEHP-treated (B, 68 mg/kg), and SIF plus DEHP-treated (D) groups. Rats were given SIF and DEHP daily through diet and gavage, respectively. After 30 d of treatment, rat urine was tested using UPLC/MS with multivariate analysis. Metabolic changes were also evaluated using biochemical assays.@*Results@#Metabolomics analyses revealed that p-cresol glucuronide, methyl hippuric acid, N1-methyl-2-pyridone-5-carboxamide, lysophosphatidycholine [18:2 (9Z, 12Z)] {lysoPC [18:2 (9Z, 12Z)]}, lysoPC (16:0), xanthosine, undecanedioic acid, and N6-acetyl-l-lysine were present at significantly different levels in control and treatment groups.@*Conclusion@#SIF supplementation partially protects rats from DEHP-induced metabolic abnormalities by regulating fatty acid metabolism, antioxidant defense system, amino acid metabolism, and is also involved in the protection of mitochondria.

18.
Journal of Leukemia & Lymphoma ; (12): 525-529, 2020.
Article in Chinese | WPRIM | ID: wpr-862879

ABSTRACT

Objective:To investigate the relationship between mitogen-activated protein kinase (MAPK) signaling pathway related signal molecules and the apoptosis of acute promyelocytic leukemia NB4 cells induced by puerariae radix flavones (PRF) and its significance.Methods:The cells were divided into control group [0.025% dimethyl sulfoxide (DMSO) to replace PRF] and 10, 30, 50 μg/ml PRF groups. The proliferation inhibition rate of NB4 cells exposed with PRF for 24, 48 and 72 hours was determined by methyl thiazolyl tetrazolium (MTT) method, and the nuclear morphology was determined by confocal laser scanning microscope after 48 hours. NB4 cells were divided into control group (adding 0.025% DMSO) and 10, 30 and 50 μg/ml PRF with or without 10 μmol/L c-Jun N-terminal kinase (JNK) inhibitor (SP600125) group, and the cells were treated for 48 hours and the changes in the expressions of MAPK pathway related proteins JNK, tumor necrosis factor α (TNF-α), extracellular signal-regulated kinase (ERK) and p38 MAPK were tested by Western blot.Results:10, 30 and 50 μg/ml PRF inhibited the proliferation of NB4 cells in 24, 48 and 72 hours, which was in time- and dose-dependent manners (all P < 0.05). The half-maximal inhibitory concentration (IC 50) at 24, 48 and 72 hours were (40.03±2.23) μg/ml, (22.92±1.72) μg/ml and (17.99±1.48) μg/ml, respectively. The confocal laser scanning microscope showed that NB4 cells displayed distinct apoptotic characteristics after PRF treatment. After co-cultivating NB4 cells with 10 μmol/L SP600125 and different concentrations of PRF for 48 hours, the expression of JNK1 in NB4 cells was suppressed ( P < 0.05), and the expressions of JNK2/3 and p38 MAPK decreased, but the differences were not statistically significant (both P > 0.05). The expressions of ERK1 and ERK2 gradually increased in the single-drug group, while the expression in the combined drug group decreased. The expression of TNF-α in the 50 μg/ml PRF+SP600125 group was down-regulated compared with the 50 μg/ml PRF single-drug group, while the expressions in the 10 and 30 μg/ml PRF+SP600125 groups were up-regulated compared with the 10 and 30 μg/ml PRF single-drug groups. Conclusion:10-50 μg/ml PRF may activate the MAPK signaling pathway through TNF-α. JNK, ERK1/2 and p38 MAPK interact with each other to activate pro-apoptotic related proteins and induce NB4 cells apoptosis.

19.
Journal of Medical Postgraduates ; (12): 1104-1109, 2019.
Article in Chinese | WPRIM | ID: wpr-818149

ABSTRACT

Osteoarthritis is a chronic progressive disease characterized by cartilage degenerative diseases. Due to the lack of vascular supply of articular cartilage and poor regeneration of chondrocytes, it is difficult to repair the cartilage with degenerative wear. A large number of studies have confirmed that bone marrow mesenchymal stem cells, adipose-derived mesenchymal stem cells, umbilical cord blood mesenchymal stem cells, umbilical cord mesenchymal stem cells, synovial mesenchymal stem cells, osteoarthritis joint fluid-derived mesenchymal stem cells, etc. can be effective to relieve osteoarthritis and repair damaged cartilage. Mesenchymal stem cells can directly differentiate into chondrocytes under appropriate microenvironment, and they also have immunosuppressive, anti-inflammatory and paracrine effects. In this paper, the research progress of basic experiments and clinical application of mesenchymal stem cells from different sources in osteoarthritis is reviewed to better promote the research progress of stem cell therapy for osteoarthritis.

20.
Article in English | WPRIM | ID: wpr-776721

ABSTRACT

Bile acids (BAs) are originally known as detergents essential for the digestion and absorption of lipids. In recent years, extensive research has unveiled new functions of BAs as gut hormones that modulate physiological and pathological processes, including glucose and lipid metabolism, energy expenditure, inflammation, tumorigenesis, cardiovascular disease, and even the central nervous system in addition to cholesterol homeostasis, enterohepatic protection and liver regeneration. BAs are closely linked with gut microbiota which might explain some of their crucial roles in organs. The signaling actions of BAs can also be mediated through specific nuclear receptors and membrane-bound G protein-coupled receptors. Several pharmacological agents or bariatric surgeries have demonstrated efficacious therapeutic effects on metabolic diseases through targeting BA signaling. In this mini-review, we summarize recent advances in bile-ology, focusing on its translational studies.

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