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1.
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.

2.
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.

3.
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.

4.
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.

5.
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)]

6.
Chinese Journal of Blood Transfusion ; (12): 95-100, 2023.
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.

7.
Shanghai Journal of Preventive Medicine ; (12): 1124-1129, 2023.
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.

8.
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 (

9.
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
10.
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.

11.
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.

12.
Chinese Journal of School Health ; (12): 167-172, 2023.
Article in Chinese | WPRIM | ID: wpr-964399

ABSTRACT

Abstract@#Allergic diseases can occur in all systems of the body, covering the whole life cycle, from children to adults and to old age, can be lifelong onset and even fatal in severe cases. Children account for the largest proportion of the victims of allergic disease, Children s allergies start from scratch, ranging from mild to severe, from less to more, from single to multiple systems and systemic performance, so the prevention and treatment of allergic diseases in children is of great importance, which can not only prevent high risk allergic conditions from developing into allergic diseases, but also further block the process of allergy. At present, there is no consensus on the management system of allergic children in kindergartens and primary schools. The "Consensus on Allergy Management and Prevention in Kindergartens and Primary Schools", which includes the organizational structure, system construction and management of allergic children, provides evidence informed recommendations for the long term comprehensive management of allergic children in kindergartens and primary schools, and provides a basis for the establishment of the prevention system for allergic children.

13.
International Eye Science ; (12): 504-507, 2023.
Article in Chinese | WPRIM | ID: wpr-964257

ABSTRACT

AIM: To observe the postoperative changes in macular morphological structure and blood flow density of patients with idiopathic macular epiretinal membrane(IMEM)by optical coherence tomography angiography(OCTA), and explore their correlation with visual acuity.METHOD: Prospective study. A total of 45 cases(45 eyes)with IMEM admitted to our hospital from January 2020 to July 2021 were included. The best corrected visual acuity(BCVA), central macular area thickness(CMT), foveal avascular zone(FAZ)area and changes in blood flow density of superficial capillary plexus(SCP)were observed at 1mo, 1, 3 and 6mo before and after operation.RESULT: The BCVA at 1wk after operation had no significant change compared with preoperative data(P>0.05), while it was improved at other time points(P<0.05). The CMT measured at 1wk after operation was thickened significantly(P<0.05), while it was significantly decreased at 1mo, 3mo and 6mo after operation(P<0.05). The FAZ area measured at 1wk and 1mo after operation had no significant change(P>0.05), while it was significantly enlarged at 3 and 6mo after operation(P<0.05). The SCP measured at 1wk, 1 and 3mo after operation had no significant change(P>0.05), while it was significantly decreased at 6mo after operation(P<0.05). BCVA measured at 3 and 6mo after operation was positively correlated with CMT(r=0.457, 0.615, P=0.032, 0.012).CONCLUSION: The visual acuity of patients with IMEM recovered quickly within 1mo after operation, and then it tended to be stable. However, the recovery of macular foveal morphology and blood flow distribution was slower than that of visual acuity, and there was no obvious correlation with visual acuity.

14.
International Eye Science ; (12): 449-455, 2023.
Article in Chinese | WPRIM | ID: wpr-964247

ABSTRACT

AIM: To explore the key genes and molecular markers involved in the retinoblastoma development through bioinformatics.METHODS: The mRNA microarray datasets from the Gene Expression Omnibus(GEO)database were obtained, and the differentially expressed gene(DEG)between retinoblastoma cell lines and normal retinal pigment epithelial(RPE)cell lines were analyzed through gene ontology(GO)and KEGG enrichment analysis. To screen key genes, establish protein-protein interaction(PPI)network, and use receiver operating characteristic(ROC)curve to assess clinical diagnostic efficacy. The RNA expressions of key genes in retinoblastoma cell lines and normal RPE cell lines were compared by qRT-PCR.RESULTS: A total of 121 DEGs were obtained from the retinoblastoma dataset of GSE97508 and GSE110811. KEGG pathway analysis showed that DEG were enriched in phototransduction, cell cycle, and p53 signaling pathways. A total of 9 key genes, including MCM6, DTL, UBE2T, TOP2A, NUSAP1, CENPK, RRM2, RLBP1, and RHO, were obtained from the intersection of PPI network analysis and the top 30 DEG from each dataset. The differentially expressed 9 key genes were verified in GSE24673. ROC analysis showed that the area under the curve(AUC)for UBE2T, RRM2, and RHO was ≥80%, and there was a statistical significance(P>0.05). The mRNA level of UBE2T and RRM2 in retinoblastoma was significantly higher than APRE-19 cell line, while the mRNA level of RHO was significantly lower than that of ARPE-19 cell line.CONCLUSION: UBE2T, RRM2, and RHO may be served as potential molecular markers and potential therapeutic targets for retinoblastoma.

15.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 9-17, 2023.
Article in Chinese | WPRIM | ID: wpr-979446

ABSTRACT

ObjectiveTo investigate the mechanism of Xumingtang in Gu Jin Lu Yan (《古今录验》) in regulating cell pyroptosis through the hypoxia-inducible factor-1α (HIF-1α)/NOD-like receptor pyrin domain-containing protein 3 (NLRP3) pathway in ischemic stroke (IS). MethodSD rats were randomly divided into a sham operation group, a model group, low- and high-dose Xumingtang groups, and a metformin group, with 20 rats in each group. Oral administration was performed for 3 days, and tissue samples were collected. Differential messenger RNA (mRNA) was screened using high-throughput sequencing, and Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed on key differentially expressed genes. The modified neurological severity score (mNSS) and 2,3,5-triphenyltetrazolium chloride (TTC) staining were used to evaluate the effect of brain infarction. Hematoxylin-eosin (HE) staining was used for pathological morphological observation of brain tissue. Enzyme-linked immunosorbent assay (ELISA) was used to compare the levels of interleukin-1β (IL-1β) and interleukin-18 (IL-18) in the ischemic cortical region. Double staining immunohistochemistry was used to detect the co-localization of HIF-1α and NLRP3. Real-time quantitative polymerase chain reaction (PCR) was performed to detect the mRNA expression of NLRP3, HIF-1α, Caspase-1 (CASP-1), and gasdermin D (GSDMD). Western blot was used to detect the protein expression of HIF-1α, NLRP3, CASP-1, and GSDMD. ResultA total of 5 705 differentially expressed genes (2 733 downregulated and 2 972 upregulated) were obtained by mRNA sequencing. After conversion to homologous genes and intersection with the pyroptosis gene set, 95 key differentially expressed pyroptosis genes were obtained. Compared with the sham operation group, the model group showed significantly increased mNSS scores, larger brain infarction areas (P<0.01), diverse neuronal morphology, disordered arrangement, widened cell gaps, significantly increased levels of IL-1β and IL-18 in the ischemic cortical region (P<0.01), enhanced co-localization fluorescence intensity, and significantly increased mRNA and protein expression levels of HIF-1α, NLRP3, CASP-1, and GSDMD (P<0.01). Compared with the model group, the high-dose Xumingtang group showed the most significant improvement in neurological function scores and brain infarction areas (P<0.01). The neuronal integrity and arrangement were more complete, and the cell gaps were narrower in all groups with drug treatment, with significantly reduced co-localization fluorescence intensity. Xumingtang could reduce the levels of IL-1β, IL-18, and the mRNA and protein expression of HIF-1α, NLRP3, CASP-1, and GSDMD (P<0.05, P<0.01), with the high-dose Xumingtang group showing the most significant effect (P<0.01). ConclusionXumingtang in Gu Jin Lu Yan can inhibit cell pyroptosis and promote neurological function recovery after IS, which may be related to the inhibition of the HIF-1α/NLRP3 pathway.

16.
Acta Pharmaceutica Sinica ; (12): 1211-1220, 2023.
Article in Chinese | WPRIM | ID: wpr-978696

ABSTRACT

The secondary metabolites of plants are important sources of natural drugs. Betula plants have abundant pharmacological value, complex mechanism and wide applications, which are closely related to the triterpenoids of theirs. Triterpenoids in Betula species are mainly divided into dammarane-type, ocotillol-type, oleanane-type, lupane-type and cycloaltunane-type. The extracts of Betula species have varieties of activities such as anti-tumor, anti-inflammatory, anti-oxidant, anti-bacterial, etc. And the biosynthetic pathways of triterpenoids after 2,3-oxidosqualene are split into four branches of dammarenediol-II, lupeol, cycloartenol and amyrin according to the different oxidosqualene cyclases. This review summarizes the chemical constituents, pharmacological activities and biosynthetic pathways of triterpenoids in Betula plants. It provides a reference for the research and development of new drugs and the production of these triterpenoids in microbial cell factories by synthetic biology methods.

17.
Acta Pharmaceutica Sinica ; (12): 1790-1801, 2023.
Article in Chinese | WPRIM | ID: wpr-978652

ABSTRACT

Plasma metabolomics based on UHPLC-Q-TOF-MS/MS technique was developed for profiling the mechanism on attenuating hepatic fibrosis of Bupleuri Radix (BR) and Paeoniae Radix Alba (PRA) before and after vinegar-processing and compatibility, and to screen potential pharmacodynamic substances by spectrum-effect correlation method in this study. Firstly, SD rats with CCl4-induced hepatic fibrosis were used as an in vivo model. The blood and tissue samples were collected for the analyses of pharmacodynamic indexes and plasma metabolomics after six weeks’ administration of BR, vinegar-processed BR (VPBR), PRA, vinegar-processed PRA (VPPRA), BR-PRA herb-pair, and VPBR-VPPRA herb-pair. The experiment was approved by the experimental animal ethics committee from Nanjing University of Chinese Medicine (No.202103A002). The results of pharmacodynamics indicated that the levels of alanine aminotransferase (ALT, P < 0.01), aspartate aminotransferase (AST, P < 0.01), and hydroxyproline (HYP, P < 0.01) were decreased significantly, while the level of glutathione peroxidase (GSH-Px, P < 0.05) was increased obviously after administration of all treatment groups. Next, UHPLC-Q-TOF-MS/MS was performed to characterize the endogenous metabolites. A total of 20 differential endogenous metabolites related to the pathogenesis of hepatic fibrosis were identified in positive and negative ion modes, mainly involving five metabolic pathways of retinol metabolism, glycerol phospholipid metabolism, glyceride metabolism, fatty acid biosynthesis, and arachidonic acid metabolism. Meanwhile, a concept named correction rate was introduced to evaluate the back-regulation effects of all treatment groups on differential metabolites, and 10 differential metabolites were corrected by all treatment groups. The correction effects of the vinegar-processed herb groups were better than those of the crude ones, and the correction effects of the herb-pair groups were better than those of the single ones. Interestingly, the best correction effect was found in the VPBR-VPPRA herb-pair group, which further verified the efficacy improvement through vinegar-processing and compatibility. Partial least square method and VIP analysis combined with spectrum-effect correlation were applied for screening pharmacodynamic markers, and 38 ingredients with higher correlation with four classical pharmacodynamic indexes (ALT, AST, HYP, and GSH-Px) were identified as pharmacodynamic markers of the anti-hepatic fibrosis effects of BR and PRA before and after vinegar-processing and compatibility. The results of the investigation could not only lay a foundation for clarifying the pharmacodynamic materials and mechanism of vinegar-processing and compatibility of BR and PRA in the treatment of hepatic fibrosis as well as provide a theoretical basis for demonstrating the scientific connotation of processing and compatibility, but also provide a reference for further drug design and development of BR and PRA in clinic.

18.
Shanghai Journal of Preventive Medicine ; (12): 219-223, 2023.
Article in Chinese | WPRIM | ID: wpr-976246

ABSTRACT

ObjectiveTo describe the characteristics of treatment outcomes of multidrug-resistant tuberculosis (MDR-TB) patients enrolled in second-line treatment in Shanghai from 2017 to 2018, and to analyze the influencing factors of treatment outcomes. MethodsTotally 182 MDR-TB patients were analyzed by using data collected from the China tuberculosis management information system, the hospital's electronic medical record information system, whole genome sequencing results and a questionnaire survey, and logistic regression analysis was used to analyze the factors affecting the success of treatment. ResultsIn 182 MDR-TB patients, the success rate of treatment was 65.4%, the loss to follow-up rate was 8.2%, the mortality rate was 4.9%, the unassessable rate was 13.7%, and the drug withdrawal rate was 7.7%. The factors affecting the success of treatment in MDR-TB patients included age (35‒ years old, OR=5.28, 95%CI: 1.58‒17.59, P=0.007; 55‒ years old, OR=16.30, 95%CI: 4.36‒60.92, P<0.001) and compliance to medication (OR=0.55, 95%CI: 0.42‒0.72, P<0.001). ConclusionThe treatment success rate of MDR-TB patients in Shanghai from 2017 to 2018 is significantly higher than the average level in China. Older patients and patients with less compliant are at higher risk of adverse treatment outcomes.

19.
Shanghai Journal of Preventive Medicine ; (12): 208-212, 2023.
Article in Chinese | WPRIM | ID: wpr-976244

ABSTRACT

ObjectiveTo evaluate the current screening methods for the students who were in close contact with tuberculosis patients, that could accurately identify the preventive treatment subjects, and to improve the tuberculosis prevention and control in Shanghai schools. MethodsThe freshman/sophomore who were in close contact with active tuberculosis patients in the colleges in 2019 were recruited. All the subjects underwent both tuberculin skin test (TST) and QuantiFERON-TB gold in-tube (QFT) test at the enrollment. After signed the informed consent, all of the participants filled in a questionnaire and determined their baseline tuberculosis infection status. They were followed up for 2 years to monitor the conversion of infection status and the incidence of tuberculosis. ResultsFour of 9 (44.4%) positive participants had conversion to negative results, and 5 of 300 (1.7%) negative participants had conversion to positive during the 2-year follow-up, one of which was diagnosed with active tuberculosis. We assessed diagnostic agreement between QFT and TST at different cut-off values. The highest coincidence rate was 94.0% when choosing 15 mm as the cut-off value, with Kappa coefficient of 0.45 (95%CI: 0.32‒0.59). ConclusionAlthough stricter than the national work requirements, the prevention and control of tuberculosis in Shanghai schools still need to be carried out meticulously. It's necessary to strengthen daily prevention and control measures, and improve the ability of management.

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Acta Pharmaceutica Sinica B ; (6): 775-786, 2023.
Article in English | WPRIM | ID: wpr-971730

ABSTRACT

The typical hallmark of tumor evolution is metabolic dysregulation. In addition to secreting immunoregulatory metabolites, tumor cells and various immune cells display different metabolic pathways and plasticity. Harnessing the metabolic differences to reduce the tumor and immunosuppressive cells while enhancing the activity of positive immunoregulatory cells is a promising strategy. We develop a nanoplatform (CLCeMOF) based on cerium metal-organic framework (CeMOF) by lactate oxidase (LOX) modification and glutaminase inhibitor (CB839) loading. The cascade catalytic reactions induced by CLCeMOF generate reactive oxygen species "storm" to elicit immune responses. Meanwhile, LOX-mediated metabolite lactate exhaustion relieves the immunosuppressive tumor microenvironment, preparing the ground for intracellular regulation. Most noticeably, the immunometabolic checkpoint blockade therapy, as a result of glutamine antagonism, is exploited for overall cell mobilization. It is found that CLCeMOF inhibited glutamine metabolism-dependent cells (tumor cells, immunosuppressive cells, etc.), increased infiltration of dendritic cells, and especially reprogrammed CD8+ T lymphocytes with considerable metabolic flexibility toward a highly activated, long-lived, and memory-like phenotype. Such an idea intervenes both metabolite (lactate) and cellular metabolic pathway, which essentially alters overall cell fates toward the desired situation. Collectively, the metabolic intervention strategy is bound to break the evolutionary adaptability of tumors for reinforced immunotherapy.

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