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1.
Chinese Pharmacological Bulletin ; (12): 447-454, 2024.
Article in Chinese | WPRIM | ID: wpr-1013636

ABSTRACT

Aim Excessive cerebral inflammation caused by chronic alcohol intake is an important risk factor for central nervous system injury. The purpose of this study was to explore the protective effect of konjac mannan oligosaccharide (KMOS) on central nervous system inflammation in alcohol-fed mice and its mechanism. Methods The chronic alcohol fed model of C57BL/6J mice was established using Gao-binge method. And the different doses of KMOS were gavaged every day for 6 weeks. The neuronal damage and microglia activation were evaluated in cerebral cortex and hippocampus. The damage of colon tissue was assessed and serum LPS concentrations were measured. In vitro, Caco-2 cells were stimulated with LPS to establish intestinal mucosal injury model. Results Chronic alcohol intake can cause brain neuron damage in mice, and different doses of KMOS effectively reduced the activation state of microglia, decreased the expression of inflammatory factors caused by the activation of the NLRP3 inflammasome and alleviated neuronal damage in the brain tissue of alcohol-fed mice. The results of colon tissue analysis showed that the use of KMOS effectively reduced the concentration of endotoxin LPS in serum of alcohol-fed mice, alleviated the pathological injury and inflammatory response of colon tissue, and enhanced the expression of Occludin in intestinal tissue. In vitro experiments also showed that KMOS significantly inhibited the inflammatory reaction of Caco-2 cells exposed to alcohol and increased the expression of Occludin protein. Conclusions KMOS treatment effectively inhibited intestinal inflammation caused by alcohol intake, repaired intestinal barrier to prevent the entry of intestinal LPS into brain tissue, decreased the activation of microglia, and then improved brain neuron damage. KMOS had the potential to prevent alcoholic nerve injury.

2.
China Pharmacy ; (12): 689-694, 2024.
Article in Chinese | WPRIM | ID: wpr-1013103

ABSTRACT

OBJECTIVE To explore the neuroprotective effect of sodium aescinate on rats with Parkinson’s disease by regulating the silent information regulator 1 (SIRT1)/nuclear factor-κB (NF-κB) signaling pathway. METHODS The Parkinson’s disease rat model was constructed by using 6-hydroxydopamine injection method. Forty-eight rats successfully modeled were randomly divided into model group, sodium aescinate low-dose group (1.8 mg/kg), sodium aescinate high-dose group (3.6 mg/kg), sodium aescinate+EX527 (sodium aescinate 3.6 mg/kg+SIRT1 inhibitor EX527 5 mg/kg) group, with 12 rats in each group. Another 12 healthy rats were selected as the sham operation group. Each group was injected with the corresponding drug solution intraperitoneally, once a day, for 21 consecutive days. Twenty-four hours after the end of the last administration, the motor and cognitive functions of rats were detected, and the morphology of neurons in the substantia nigra and CA1 region of hippocampal tissue were observed. The content of dopamine (DA) in the nigrostriatal and the expression levels of tyrosine hydroxylase (TH) and α-synuclein (α-Syn) in the substantia nigra were detected. The serum levels of pro-inflammatory factor [interleukin-6 (IL-6), IL-18], anti-inflammatory factor (IL-10), and the expression levels of SIRT1, phosphorylated NF-κB p65 (p-NF-κB p65) and NF- κB p65 protein in nigrostriatal were detected. RESULTS Compared with sham operation group, the neurons in the substantia nigra and CA1 region of hippocampal tissue were seriously damaged in model group; the number of rotations, escape latency, the expression levels of α-Syn in substantia nigra, the levels of serum pro-inflammatory factors, the relative expression ratio of p-NF- κB p65 and NF-κB p65 protein in nigrostriatal were increased or prolonged significantly (P<0.05); the target quadrant residence time, the content of DA in nigrostriatal, the expression level of TH in substantia nigra, the serum level of anti-inflammatory factor, and the expression level of SIRT1 protein in substantia nigra striatum were significantly decreased or shortened (P<0.05). Compared with model group, the damage degrees of neuron in sodium aescinate groups were alleviated, and the quantitative indicators were significantly improved, which were more significant in the high-dose group (P<0.05); EX527 could reverse the improvement effect of high-dose sodium aescinate (P<0.05). CONCLUSIONS Sodium aescinate can inhibit the activation of NF-κB signal by up-regulating the protein expression of SIRT1, thereby reducing the neuroinflammation of rats with Parkinson’s disease, improving the motor and cognitive dysfunctions, and finally playing a neuroprotective role.

3.
China Pharmacy ; (12): 186-191, 2024.
Article in Chinese | WPRIM | ID: wpr-1006176

ABSTRACT

OBJECTIVE To investigate the inhibitory effects of Ginkgo biloba extract (GBE) on renal inflammation in diabetic nephropathy (DN) model mice, and its potential mechanism. METHODS KK/Ay mice were fed with high fat and high sugar to induce DN model. They were divided into model group, positive control group [metformin 200 mg/(kg·d)], GBE low-dose and high-dose groups [100, 200 mg/(kg·d)], with 6 mice in each group. Six C57BL/6J mice were fed with a regular diet as the control group. Administration groups were given relevant liquid intragastrically, control group and model group were given constant volume of normal saline intragastrically, once a day, for 8 consecutive weeks. The body weight, fasting blood glucose, 24-hour food intake, 24-hour urine output, monocyte chemoattractant protein-1 (MCP-1), interleukin-12 (IL-12), IL-10, advanced glycation end products (AGEs), blood urea nitrogen (BUN) and serum creatinine (Scr) of mice were measured, and the ratio of bilateral kidneys to body weight was also calculated. The pathological injury and fibrotic changes of the renal cortex were observed, and the expressions of macrophage polarization marker proteins [type M1: inducible nitric oxide synthase (iNOS); type M2: arginase-1 (Arg-1)] and AGEs-the receptor of advanced glycation end products (RAGE)/Ras homolog gene pharm_chenjing@163.com family member A (RhoA)/Rho-associated coiled-coil forming protein kinase (ROCK) signaling pathway-related proteins were determined in renal cortex. RESULTS Compared with the model group, the symptoms such as renal cortical hyperplasia, vacuoles, infiltration of inflammatory cells, and renal cortical fibrosis had been improved in GBE low-dose and high-dose groups; body weight, serum level of IL-10, the expression of Arg-1 in the renal cortex were significantly higher than model group (P< 0.01); fasting blood glucose, 24-hour food intake, 24-hour urine output, serum levels of MCP-1, IL-12, BUN, Scr and AGEs, the ratio of bilateral kidneys to body weight, renal injury score, the proportion of renal interstitial fibrosis, the protein expressions of iNOS, RAGE, RhoA and ROCK1 (except for GBE low-dose group) in renal cortex were significantly lower than model group (P<0.01). CONCLUSIONS GBE could improve kidney damage and alleviate inflammatory response in DN model mice, the mechanism of which may be related to inhibiting the AGEs-RAGE/RhoA/ROCK signaling pathway and regulating macrophage polarization.

4.
Acta Anatomica Sinica ; (6): 313-318, 2023.
Article in Chinese | WPRIM | ID: wpr-1015220

ABSTRACT

[ Abstract] Objective To investigate the relationship between single nucleotide polymorphism (SNP) Fok (rs2228570 / rs10735810) of vitamin D receptor (VDR) gene and hypertensive disorder complicating pregnancy (HDCP) in Han nationality women of Qinghai province. Methods A total of 137 Han nationality HDCP subjects (HDCP group) and 146 Han nationality normal pregnant subjects (control group) were selected from Qinghai province. The Fok polymorphism typing in HCDP group and control group was analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) . The mutation was confirmed by sequencing. SPSS 19. 0 statistical software was used to test whether there were significant differences between two groups in general clinical data, genotype and allele frequency distribution. Results The frequency of FF Ff ff genotype of Fok in HDCP group and control group were 51. 82%, 37. 96%, 10. 22% and 34. 93%, 43. 15%, 21. 92% respectively (

5.
Chinese Journal of Pediatrics ; (12): 889-895, 2023.
Article in Chinese | WPRIM | ID: wpr-1013193

ABSTRACT

Objective: To analyze the clinical and molecular diagnostic status of Fanconi anemia (FA) in China. Methods: The General situation, clinical manifestations and chromosome breakage test and genetic test results of 107 pediatric FA cases registered in the Chinese Blood and Marrow Transplantation Registry Group (CBMTRG) and the Chinese Children Blood and Marrow Transplantation Registry Group (CCBMTRG) from August 2009 to January 2022 were analyzed retrospectively. Children with FANCA gene variants were divided into mild and severe groups based on the type of variant, and Wilcoxon-test was used to compare the phenotypic differences between groups. Results: Of the 176 registered FA patients, 69 (39.2%) cases were excluded due to lack of definitive genetic diagnosis results, and the remaining 107 children from 15 hospitals were included in the study, including 70 males and 37 females. The age at transplantation treatment were 6 (4, 9) years. The enrolled children were involved in 10 pathogenic genes, including 89 cases of FANCA gene, 7 cases of FANCG gene, 3 cases of FANCB gene, 2 cases of FANCE gene and 1 case each of FANCC, FANCD1, FANCD2, FANCF, FANCJ, and FANCN gene. Compound heterozygous or homozygous of loss-of-function variants account for 69.2% (72/104). Loss-of-function variants account for 79.2% (141/178) in FANCA gene variants, and 20.8% (37/178) were large exon deletions. Fifty-five children (51.4%) had chromosome breakage test records, with a positive rate of 81.8% (45/55). There were 172 congenital malformations in 80 children.Café-au-Lait spots (16.3%, 28/172), thumb deformities (16.3%,28/172), polydactyly (13.9%, 24/172), and short stature (12.2%, 21/172) were the most common congenital malformations in Chinese children with FA. No significant difference was found in the number of congenital malformations between children with severe (50 cases) and mild FANCA variants (26 cases) (Z=-1.33, P=0.185). Conclusions: FANCA gene is the main pathogenic gene in children with FA, where the detection of its exon deletion should be strengthened clinically. There were no phenotypic differences among children with different types of FANCA variants. Chromosome break test is helpful to determine the pathogenicity of variants, but its accuracy needs to be improved.


Subject(s)
Male , Female , Humans , Child , Fanconi Anemia/genetics , Chromosome Breakage , Retrospective Studies , Exons , China/epidemiology
6.
Acta Pharmaceutica Sinica B ; (6): 4999-5015, 2023.
Article in English | WPRIM | ID: wpr-1011210

ABSTRACT

The promise of regeneration therapy for restoration of damaged myocardium after cardiac ischemic injury relies on targeted delivery of proliferative molecules into cardiomyocytes whose healing benefits are still limited owing to severe immune microenvironment due to local high concentration of proinflammatory cytokines. Optimal therapeutic strategies are therefore in urgent need to both modulate local immunity and deliver proliferative molecules. Here, we addressed this unmet need by developing neutrophil-mimic nanoparticles NM@miR, fabricated by coating hybrid neutrophil membranes with artificial lipids onto mesoporous silica nanoparticles (MSNs) loaded with microRNA-10b. The hybrid membrane could endow nanoparticles with strong capacity to migrate into inflammatory sites and neutralize proinflammatory cytokines and increase the delivery efficiency of microRNA-10b into adult mammalian cardiomyocytes (CMs) by fusing with cell membranes and leading to the release of MSNs-miR into cytosol. Upon NM@miR administration, this nanoparticle could home to the injured myocardium, restore the local immunity, and efficiently deliver microRNA-10b to cardiomyocytes, which could reduce the activation of Hippo-YAP pathway mediated by excessive cytokines and exert the best proliferative effect of miR-10b. This combination therapy could finally improve cardiac function and mitigate ventricular remodeling. Consequently, this work offers a combination strategy of immunity modulation and proliferative molecule delivery to boost cardiac regeneration after injury.

7.
Acta Pharmaceutica Sinica ; (12): 571-580, 2023.
Article in Chinese | WPRIM | ID: wpr-965624

ABSTRACT

Sphingosine kinase (SphK), sphingosine-1-phosphate (S1P) and S1P receptor (S1PR) are involved in the tumor biological processes such as tumor cell proliferation and migration, and play an important role in the development of cancer. In recent years, researchers have increasingly focused on the interaction between cancer cells and the tumor microenvironment. The tumor microenvironment is genetically stable and can be induced to an antitumor phenotype, which has significant therapeutic advantages. Studies have shown that SphK/S1P/S1PR can regulate multiple aspects of the tumor microenvironment. This review summarizes the effects of SphK and S1P/S1PR signaling on the tumor microenvironment from four perspectives: tumor immune microenvironment, cancer associated fibroblasts, tumor angiogenesis and tumor hypoxic microenvironment, and also outlines potential drug research related to these signal molecules, aiming to elucidate the role of SphK/S1P/S1PR in tumor occurrence and development and provide new ideas for the research of anti-tumor drugs.

8.
Sichuan Mental Health ; (6): 547-551, 2023.
Article in Chinese | WPRIM | ID: wpr-1005291

ABSTRACT

BackgroundThe persistently high prevalence of insomnia seriously affects the quality of life of all populations. Studies showed that state-trait anxiety, resilience and neuroticism are related to the occurrence of insomnia, while the research on the relationship among the four factors in college students is still insufficient. ObjectiveTo discuss the impact of neuroticism on insomnia among college students, and to examine the mediating role of state-trait anxiety and resilience in the relationship between neuroticism and insomnia, thus providing references for the intervention of insomnia in college students. MethodsFrom September to December 2020, simple random sampling techniques were utilized to select 1 416 students in a university in Sichuan province, and all subjects were assessed using State-Trait Anxiety Inventory (STAI), Connor-Davidson Resilience Scale (CD-RISC), Chinese Big Five Personality Inventory-15 (CBF-PI-15) and Insomnia Severity Index (ISI). Then Pearson correlation analysis was conducted to examine the correlation among the above four scales, and the mediating role of STAI and CD-RISC in the relationship between CBF-PI-15 neuroticism dimension and ISI was verified by Process macro mediation analysis. ResultsInsomnia was reported in 241/1 416 (17.02%) college students. The prevalence rate of insomnia in male students was higher than that in female students, with statistical difference (χ2=16.417, P<0.01). Total ISI score was positively correlated with CBF-PI-15 neuroticism dimension and total STAI score (r=0.127, 0.563, P<0.01), and negatively correlated with total CD-RISC score (r=-0.149, P<0.01). State-trait anxiety and resilience of college students had a chain mediation effect on the relationship between neuroticism and insomnia (indirect effect size was -0.011), and the size of direct effect of neuroticism on insomnia was 0.120, accounting for 75.00% of the total effect. ConclusionState-trait anxiety and resilience of college students exert a chain mediation effect on the relationship between neuroticism and insomnia, so the neuroticism causes an impact on insomnia both directly and indirectly through the chain mediating effect of state-trait anxiety and resilience.

9.
Sichuan Mental Health ; (6): 521-526, 2023.
Article in Chinese | WPRIM | ID: wpr-1005287

ABSTRACT

BackgroundThe schizophrenia is majorly treated with drug and through physical therapy. However, both treatments would lead to adverse reactions, which could affect therapy adherence and treatment efficacy. Previous studies have shown that aerobic exercise can help alleviate cognitive function in patients with Alzheimer's disease and depressive disorder. At present, little research has been done on such alleviation in schizophrenia patients. ObjectiveTo explore the effect of aerobic exercise on cognitive function in male patients with chronic schizophrenia, so as to provide references for relevant treatments. MethodsA total of 76 male patients with chronic schizophrenia hospitalized in the Fourth People's Hospital of Wuhu between December 2022 and April 2023 were selected as the study subjects and, in accordance with random number table, divided into study group (n=36) and control group (n=40). Both groups received conventional drug treatment. On this basis, the study group received a 60-minute aerobic exercise 5 times a week for 8 weeks as intervention. Before and after intervention, assessment of cognitive function was performed by using MATRICS Consensus Cognitive Battery (MCCB) and Stroop Color Word Test (SCWT). ResultAfter intervention, compared with the control group, the study group spent less time on finishing the Trail Making Test and scored higher in both the spatial span test and maze test (Z=-2.070, -2.306, -2.375, P<0.05). Repeated measure ANOVA results showed that the time main effect of Hopkins Verbal Learning Test score was statistically significant in the two groups after intervention (F=39.067, P<0.05). So was the interaction effect between the time and group of the Brief Visuospatial Memory Test and Verbal Fluency Test scores (F=10.092, 9.252, P<0.05). After intervention, the scores of the Brief Visuospatial Memory Test and Verbal Fluency Test in the study group were higher than those in the control group (t=6.689, 4.249, P<0.05). As for the study group itself, the scores were higher than those before intervention (t=23.746, 23.842, P<0.05). After intervention, the numbers of correct reading in color test and word test in the study group were more than those in the control group (Z=-2.358, -2.771, P<0.05). The interaction effect between the time and group of the reaction time in color test, word test and color word interference test were statistically significant in both groups (F=23.383, 19.888, 19.662, P<0.05). After intervention, the reaction time in color test and color word interference test of the study group was shorter than those of the control group (t=4.895, 6.163, P<0.05). As for the study group itself, the reaction time were shorter than before intervention (t=54.318, 42.425, 42.141, P<0.01). ConclusionAerobic exercise may help alleviate the cognitive problems in male patients with chronic schizophrenia in terms of information processing speed, working memory, reasoning/problem solving ability, word learning and memorizing, visual learning and memorizing, and executive function. [Funded by Wuhu Science and Technology Plan Project (number, 2021jc2-3)]

10.
Article in Chinese | WPRIM | ID: wpr-1004849

ABSTRACT

Autologous ozonized blood transfusion(AOBT) is a therapy of re-transfusion of 100-200 mL of autologous blood after shaking and agitation with appropriate amount of oxygen-ozone in vitro. The oxidation of blood through the strong oxidation of ozone can enhance the non-specific immune response of the body, regulate the internal environment and promote health. This therapy has been increasingly applied in clinical practice, while no unified standard for the operation process in terms of ozone concentration, treatment frequency and treatment course had been established. This operation process of AOBT is primarily explored in order to standardize the operation process and ensure its safety and efficacy.

11.
Article in Chinese | WPRIM | ID: wpr-1003821

ABSTRACT

A group of compounds structurally related to tetrahydrocannabinol or capable of binding to cannabinoid receptors are collectively referred to as cannabinoids. Cannabinoids can be divided into plant derived cannabinoids, synthetic cannabinoids, and endogenous cannabinoids. Δ-9-THC is the only psychoactive compound in plant cannabinoids. Cannabis with Δ-9-THC>0.3% is internationally listed as a prohibited drug, while cannabis with Δ-9-THC<0.3% is industrial cannabis. Due to its low addiction and high commercial value, it is allowed to be added to food in many countries. More and more industrial cannabis foods become popular, and the detection/analysis of cannabinoid compounds in cannabis foods is particularly important; In addition to industrial cannabis, which is widely used in food, there are also various new drugs, synthetic cannabinoids, disguised as conventional food, which can cause the social problems and increase the food safety risks. This article will elaborate on the regulatory status of cannabinoid compounds in food, In order to promote the safety supervision of the domestic cannabis food.

12.
Journal of Forensic Medicine ; (6): 447-451, 2023.
Article in English | WPRIM | ID: wpr-1009376

ABSTRACT

OBJECTIVES@#To establish the menstrual blood identification model based on Naïve Bayes and multivariate logistic regression methods by using specific mRNA markers in menstrual blood detection technology combined with statistical methods, and to quantitatively distinguish menstrual blood from other body fluids.@*METHODS@#Body fluids including 86 menstrual blood, 48 peripheral blood, 48 vaginal secretions, 24 semen and 24 saliva samples were collected. RNA of the samples was extracted and cDNA was obtained by reverse transcription. Five menstrual blood-specific markers including members of the matrix metalloproteinase (MMP) family MMP3, MMP7, MMP11, progestogens associated endometrial protein (PAEP) and stanniocalcin-1 (STC1) were amplified and analyzed by electrophoresis. The results were analyzed by Naïve Bayes and multivariate logistic regression.@*RESULTS@#The accuracy of the classification model constructed was 88.37% by Naïve Bayes and 91.86% by multivariate logistic regression. In non-menstrual blood samples, the distinguishing accuracy of peripheral blood, saliva and semen was generally higher than 90%, while the distinguishing accuracy of vaginal secretions was lower, which were 16.67% and 33.33%, respectively.@*CONCLUSIONS@#The mRNA detection technology combined with statistical methods can be used to establish a classification and discrimination model for menstrual blood, which can distignuish the menstrual blood and other body fluids, and quantitative description of analysis results, which has a certain application value in body fluid stain identification.


Subject(s)
Female , Humans , RNA, Messenger/metabolism , Bayes Theorem , Logistic Models , Menstruation , Body Fluids , Saliva , Semen , Forensic Genetics/methods
13.
Article in Chinese | WPRIM | ID: wpr-1009327

ABSTRACT

OBJECTIVE@#To explore the long-term efficacy of allogeneic hematopoietic stem cell transplantation (alloHSCT) in patients with Mucopolysaccharidosis (MPS), which has rarely been reported in China.@*METHODS@#A 18-month-old boy and a 23-month-old girl undergoing alloHSCT for MPS VI and MPS IH Shanghai Children's Medical Center on March 30, 2006 and September 6, 2006 were selected as the study subjects. A busulfan-based myeloablative regimen was used as the conditioning regimen. Peripheral stem cells were respectively collected from a human leucocyte antigen (HLA) matched sibling carrier donor and a HLA 9/10 matched unrelated donor. Both patients were followed up for more than 15 years. The functions of internal organs before and after the transplantation were compared, and child 1 was also compared with his untreated brother and healthy brother.@*RESULTS@#Both children have achieved full donor chimerism after the transplantation, and their enzymatic activities have remained stable. The enzymatic activity of the child 1 was slightly lower than normal but similar to that of his carrier donor, whilst that of the child 2 was normal. Both children have attended schools with good academic performance. Compared with his untreated brother, the respiratory function and hearing of child 1 have significantly improved. However, his orthopedic and cardiac disorders have still remained and required medical intervention. For child 2, her obstructive pulmonary disease was resolved and cognitive development was well preserved after the HSCT. Her heart disease has become stabilized and even improved with time, though her corneal clouding and skeletal malformation still required surgery.@*CONCLUSION@#MPS patients can sustain long-term and stable enzymatic activities after successful alloHSCT. Compared with untreated patients, their health can be significantly improved, along with considerably prolonged survival, though the long-term efficacy of HSCT for different organs may vary to a certain extent.


Subject(s)
Humans , Child , Male , Female , Infant , Child, Preschool , Graft vs Host Disease/etiology , China , Hematopoietic Stem Cell Transplantation/adverse effects , Mucopolysaccharidoses/etiology , Busulfan , Treatment Outcome
14.
Article in English | WPRIM | ID: wpr-1008990

ABSTRACT

This data article presents data from the China Migrants Dynamic Survey (CMDS), a multi-wave, large-scale national cross-sectional survey of China's internal migrants from 2009 to 2018. The CMDS is an annual questionnaire survey conducted by the former National Health and Family Planning Commission (NHFPC) of the People's Republic of China. The respondents included in this survey are internal migrants over 15 years old. The sample was drawn from the China Migrant Population Information System, using multi-stage stratified sampling method and the probability proportional-to-size (PPS) cluster sampling strategy. Between 2009 and 2018, there were 1,527,650 internal migrants from 23 provinces, 5 autonomous regions and 4 municipalities participated in the surveys. The survey tools were a series of self-designed questionnaires with high inheritance and consistency designed and implemented by the NHFPC. The questionnaires mainly contain basic information of the respondents and their family members, migration status, healthcare or health behaviors, public health service utilization, social insurance, social integration, and family planning. The dataset is currently the most widely used survey data on China's internal migrants, offering information on migration patterns, healthcare and health behaviors, use of public health services, access to social security, social integration, and family planning, which are valuable for health planning, health decision-making, and health equity research.


Subject(s)
Humans , Adolescent , United States , Family Planning Services , Transients and Migrants , Cross-Sectional Studies , China/epidemiology , Surveys and Questionnaires
15.
Article in Chinese | WPRIM | ID: wpr-1008867

ABSTRACT

This study investigated the effect of eleutheroside B on apoptosis and autophagy of lung cancer A549 and H460 cells and its molecular mechanism. MTT assay was used to detect the cytotoxicity of eleutheroside B at 5, 10, 15, 20, 25, 30, 35, 40, and 45 mmol·L~(-1) on lung cancer cells. Trypan blue exclusion assay was used to detect the effect of eleutheroside B on the survival rate of lung cancer A549 and H460 cells at different time. Colony formation assay was used to detect the effect of eleutheroside B on the proliferation of lung cancer A549 and H460 cells. AO/EB fluorescence double staining and Hoechst 33342 fluorescence staining were used to detect the effect of eleutheroside B on apoptosis of lung cancer A549 and H460 cells, and Western blot was used to detect apoptosis-related proteins to explore the apoptosis-related molecular mechanism. AO fluorescence staining and Western blot were used to detect the expression of autophagic vesicles and autophagy-related proteins P62 and LC3. The results showed that compared with the control group, eleutheroside B inhibited the growth of lung cancer A549 and H460 cells in a concentration-dependent manner. The optimal effect time of eleutheroside B on lung cancer A549 and H460 cells was 24 h, and the optimal concentrations were 28.64 and 22.16 mmol·L~(-1), respectively. Eleutheroside B could inhibit the colony formation of A549 and H460 cells. Compared with the control group, eleutheroside B could promote the formation of apoptotic bodies and induce cell apoptosis, as well as induce the expression of mitochondrial pathway-related proteins. Under the effect of eleutheroside B, the acidic autophagy vacuole in lung cancer cells increased, LC3Ⅱ expression increased, P62 protein expression decreased, and PI3K, p-Akt, and p-mTOR protein expression decreased in the PI3K/Akt/mTOR pathway. Studies have shown that eleutheroside B can inhibit the growth of lung cancer cells, reduce colony formation, induce apoptosis of lung cancer cells through mitochondrial pathway, and induce autophagy. The mechanism may be related to the PI3K/Akt/mTOR pathway.


Subject(s)
Humans , Lung Neoplasms/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , Apoptosis , Apoptosis Regulatory Proteins , Autophagy , Cell Proliferation , Cell Line, Tumor , Glucosides , Phenylpropionates
16.
Article in Chinese | WPRIM | ID: wpr-986988

ABSTRACT

OBJECTIVE@#To predict the targets and pathways in the therapeutic mechanism of Guizhi Gancao Decoction (GZGCD) against heart failure (HF) based on network pharmacology.@*METHODS@#The chemical components of GZGCD were analyzed using the databases including TCMSP, TCMID and TCM@Taiwan, and the potential targets of GZGCD were predicted using the SwissTargetPrediction database. The targets of HF were obtained using the databases including DisGeNET, Drugbank and TTD. The intersection targets of GZGCD and HF were identified using VENNY. Uniport database was used to convert the information, and the components-targets-disease network was constructed using Cytoscape software. The Bisogene plug-in, Merge plug-in, and CytoNCA plug-in in Cytoscape software were used for protein-protein interaction (PPI) analysis to acquire the core targets. Metascape database was used for GO and KEGG analysis. The results of network pharmacology analysis were verified with Western blot analysis. Three factors (PKCα, ERK1/2 and BCL2) were screened according to the degree value of network pharmacology results and the degree of correlation with heart failure process. The pentobarbtal sodium was dissolvein H9C2 cells treated with serum-free high glucose medium to simulate the ischemic anoxic environment of heart failure. The total proteins of myocardial cells were extracted. The protein contents of PKCα, ERK1/2 and BCL2 were determined.@*RESULTS@#We identified a total of 190 intersection targets between GZGCD and HF using Venny database, involving mainly the circulatory system process, cellular response to nitrogen compounds, cation homeostasis, and regulation of the MAPK cascade. These potential targets were also involved in 38 pathways, including the regulatory pathways in cancer, calcium signal pathway, cGMP-PKG signal pathway, and cAMP signal pathway. Western blot analysis showed that in an in vitro H9C2 cell model of HF, treatment with GZGCD downregulated PKCα and ERK1/2 expressions and upregulated BCL2 expression.@*CONCLUSION@#The therapeutic mechanism of GZGCD for HF involves multiple targets including PRKCA, PRKCB, MAPK1, MAPK3, and MAPK8 and multiple pathways including the regulatory pathway in cancer and the calcium signaling pathway.


Subject(s)
Humans , Protein Kinase C-alpha , Network Pharmacology , Heart Failure/drug therapy , Proto-Oncogene Proteins c-bcl-2
17.
Article in Chinese | WPRIM | ID: wpr-986873

ABSTRACT

OBJECTIVE@#To explore the association between rs2587552 polymorphism (has a strong lin-kage disequilibrium with rs1800497 which had been found in many studies to be related to obesity, r2=0.85) of DRD2 gene and the effect of a childhood obesity intervention in Chinese population, and provide a scientific basis for future personalized childhood obesity intervention based on genetic background.@*METHODS@#From a multi-center cluster randomized controlled trial studying the effect of a childhood obesity intervention, we enrolled 382 children from 8 primary schools (192 and 190 children from intervention and control groups, respectively) in Beijing as study subjects. Saliva was collected and DNA was extracted to detect the rs2587552 polymorphism of DRD2 gene, and the interactions between the gene and study arms on childhood obesity indicators [including body weight, body mass index (BMI), BMI Z-score, waist circumference, hip circumference, waist-to-hip ratio, waist-to-height ratio, and body fat percentage] were analyzed.@*RESULTS@#No association was found between rs2587552 polymorphism and the changes in hip circumference or body fat percentage in the intervention group (P>0.05). However, in the control group, children carrying the A allele at DRD2 rs2587552 locus showed a greater increase in hip circumference and body fat percentage compared with those not carrying A allele (P < 0.001). There were interactions between rs2587552 polymorphism of DRD2 gene and study arms on the changes in hip circumference and body fat percentage (P=0.007 and 0.015, respectively). Compared with the control group, children in the intervention group carrying the A allele at DRD2 rs2587552 locus showed decrease in hip circumference by (-1.30 cm, 95%CI: -2.25 to -0.35, P=0.007) and decrease in body fat percentage by (-1.34%, 95%CI: -2.42 to -0.27, P=0.015) compared with those not carrying A allele. The results were consistent between the dominant model and the additive model (hip circumfe-rence: -0.66 cm, 95%CI: -1.28 to -0.03, P=0.041; body fat percentage: -0.69%, 95%CI: -1.40 to 0.02, P=0.056). No interaction was found between rs2587552 polymorphism and study arms on the changes in other childhood obesity-related indicators (P>0.05).@*CONCLUSION@#Children carrying the A allele at rs2587552 polymorphism of DRD2 gene are more sensitive to intervention and showed more improvement in hip circumference and body fat percentage after the intervention, suggesting that future personalized childhood obesity lifestyle intervention can be carried out based on the rs2587552 polymorphism of DRD2 gene.


Subject(s)
Humans , Child , Pediatric Obesity/therapy , Prospective Studies , Polymorphism, Genetic , Body Mass Index , Waist Circumference , Receptors, Dopamine D2/genetics
18.
Article in Chinese | WPRIM | ID: wpr-985955

ABSTRACT

Objective: To assess the efficacy and cost-effectiveness of high-dose dual therapy compared with bismuth-containing quadruple therapy for treating Helicobacter pylori(H.pylori) infection in servicemen patients. Methods: A total of 160 H. pylori-infected, treatment-naive servicemen, including 74 men and 86 women, aged from 20 years to 74 years, with a mean (SD) age of 43 (13) years, tested in the First Center of Chinese PLA General Hospital from March 2022 to May 2022 were enrolled in this open-label, randomized controlled clinical trial. Patients were randomly allocated into 2 groups: the 14-day high-dose dual therapy group and the bismuth-containing quadruple therapy group. Eradication rates, adverse events, patient compliance, and drug costs were compared between the two groups. The t-test was used for continuous variables, and the Chi-square test for categorical variables. Results: No significant difference in H. pylori eradication rates were found between high-dose dual therapy and bismuth-containing quadruple therapy by ITT, mITT and PP analysis[ITT:90.0% (95%CI 81.2%-95.6%) vs. 87.5% (95%CI 78.2%-93.8%), χ2=0.25, P=0.617;mITT:93.5% (95%CI 85.5%-97.9%) vs. 93.3% (95%CI 85.1%-97.8%), χ2<0.01, P=1.000; PP: 93.5% (95%CI 85.5%-97.9%) vs. 94.5% (95%CI 86.6%-98.5%), χ2<0.01, P=1.000 ]. The dual therapy group exhibited significantly less overall side effects compared with the quadruple therapy group [21.8% (17/78) vs. 38.5% (30/78), χ2=5.15,P=0.023]. There were no significant differences in the compliance rates between the two groups [98.7%(77/78) vs. 94.9%(74/78), χ2=0.83,P=0.363]. The cost of medications in the dual therapy was 32.0% lower compared with that in the quadruple therapy (472.10 RMB vs. 693.94 RMB). Conclusions: The dual regimen has a favorable effect on the eradication of H. pylori infection in servicemen patients. Based on the ITT analysis, the eradication rate of the dual regimen is grade B (90%, good). Additionally, it exhibited a lower incidence of adverse events, better compliance and significantly reduced cost. The dual regimen is expected to be a new choice for the first-line treatment of H. pylori infection in servicemen but needs further evaluation.


Subject(s)
Male , Humans , Female , Young Adult , Adult , Helicobacter Infections , Helicobacter pylori , Bismuth , Anti-Bacterial Agents/therapeutic use , Amoxicillin/adverse effects , Drug Therapy, Combination , Treatment Outcome , Proton Pump Inhibitors/therapeutic use
19.
Chinese Journal of Pediatrics ; (12): 351-356, 2023.
Article in Chinese | WPRIM | ID: wpr-985875

ABSTRACT

Objective: To evaluate the therapeutic efficacy of hematopoietic stem cell transplantation (HSCT) for Wiskott-Aldrich syndrome (WAS), and to analyze the factors related to the outcomes. Methods: The clinical data of 60 children with WAS received HSCT in Shanghai Children's Medical Center from January 2006 to December 2020 were retrospectively analyzed. All cases were treated with a myeloablative conditioning regimen with busulfan and cyclophosphamide, and a graft-versus-host disease (GVHD) prevention regimen based on cyclosporine and methotrexate. Implantation, GVHD, transplant-related complications, immune reconstitution and survival rate were observed. Survival analysis was performed by Kaplan-Meier method, and Log-Rank method was used for univariate comparison. Results: The 60 male patients had main clinical features as infection and bleeding. The age at diagnosis was 0.4 (0.3, 0.8) years, and the age at transplantation was 1.1 (0.6, 2.1) years. There were 20 cases of human leukocyte antigen matched transplantation and 40 mismatched transplantation; 35 patients received peripheral blood HSCT, and 25 cord blood HSCT. All cases were fully implanted. The incidence of acute GVHD (aGVHD) was 48% (29/60) and only 2 (7%) developed aGVHD of grade Ⅲ; the incidence of chronic GVHD (cGVHD) was 23% (13/56), and all cases were limited. The incidence of CMV and EBV infection was 35% (21/60) and 33% (20/60) respectively; and 7 patients developed CMV retinitis. The incidence of sinus obstruction syndrome was 8% (5/60), of whom 2 patients died. There were 7 cases (12%) of autoimmune hemocytopenia after transplantation. Natural killer cells were the earliest to recover after transplantation, and B cells and CD4+T cells returned to normal at about 180 days post HSCT. The 5-year overall survival rate (OS) of this group was 93% (95%CI 86%-99%), and the event free survial rate (EFS) was 87% (95%CI 78%-95%). EFS of non-CMV reactivation group is higher than that of CMV reactivation group (95% (37/39) vs.71% (15/21), χ2=5.22, P=0.022). Conclusions: The therapeutic efficacy of HSCT for WAS is satisfying, and the early application of HSCT in typical cases can achieve better outcome. CMV infection is the main factor affecting disease-free survival rate, which can be improved by strengthening the management of complications.


Subject(s)
Humans , Male , Child , Retrospective Studies , Wiskott-Aldrich Syndrome/therapy , China , Hematopoietic Stem Cell Transplantation/methods , Graft vs Host Disease/prevention & control , Transplantation Conditioning
20.
Chinese Journal of School Health ; (12): 1230-1233, 2023.
Article in Chinese | WPRIM | ID: wpr-985595

ABSTRACT

Objective@#To investigate the current situation of obesity and related metabolic abnormalities among preschool children, so as to provide theoretical support for future intervention.@*Methods@#A cohort of 3 952 children, born in Tianjin and enrolled in the kindergarten from September 2017 to October 2018, were selected to conduct a baseline survey and a three-year follow-up (questionnaire survey, physical examination and laboratory testing). At the same time, a two-way cohort study was conducted to retrospectively collect maternal prenatal examination, delivery and regular physical examination information of children from birth to preschool age from Tianjin Maternal and Child Health Information System.@*Results@#A total of 3 935, 3 654 and 2 739 children completed the follow up in the primary, middle and senior classes of kindergarten respectively. The height and weight of pre-school children increased with age, while the percentage of body fat decreased with age ( β-trend =-0.74, P <0.01). During three-year follow up, height, weight and body mass index of boys were higher than girls (P<0.05), while the percentage of body fat was lower than girls (primary class: 17.5%,18.5%; middle class: 16.4%,17.2%; senior class: 16.1%,17.1%, P <0.05). The detection rate of overweight (including obesity) and obesity increased with age( χ 2 trend were 15.51,38.72, P <0.05). The total detection rate of obesity increased from 5.4% at the baseline level to 9.6%. Laboratory test results showed that the detection rates of fasting blood glucose of boys were higher than that of girls in primary class, but blood lipid abnormalities were in the opposite (glucose: 7.7%, 4.8 %; lipid: 23.8% , 27.7%)( χ 2=12.01, 6.63, P <0.05).@*Conclusion@#The study has established a large growth cohort starting from the early embryonic stage, which will help to establish the strategies to promote children s health and prevent obesity and chronic diseases from multidimensional perspectives.

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