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RNA editing, an essential post-transcriptional reaction occurring in double-stranded RNA (dsRNA), generates informational diversity in the transcriptome and proteome. In mammals, the main type of RNA editing is the conversion of adenosine to inosine (A-to-I), processed by adenosine deaminases acting on the RNAs (ADARs) family, and interpreted as guanosine during nucleotide base-pairing. It has been reported that millions of nucleotide sites in human transcriptome undergo A-to-I editing events, catalyzed by the primarily responsible enzyme, ADAR1. In hematological malignancies including myeloid/lymphocytic leukemia and multiple myeloma, dysregulation of ADAR1 directly impacts the A-to-I editing states occurring in coding regions, non-coding regions, and immature miRNA precursors. Subsequently, aberrant A-to-I editing states result in altered molecular events, such as protein-coding sequence changes, intron retention, alternative splicing, and miRNA biogenesis inhibition. As a vital factor of the generation and stemness maintenance in leukemia stem cells (LSCs), disordered RNA editing drives the chaos of molecular regulatory network and ultimately promotes the cell proliferation, apoptosis inhibition and drug resistance. At present, novel drugs designed to target RNA editing(e.g., rebecsinib) are under development and have achieved outstanding results in animal experiments. Compared with traditional antitumor drugs, epigenetic antitumor drugs are expected to overcome the shackle of drug resistance and recurrence in hematological malignancies, and provide new treatment options for patients. This review summarized the recent advances in the regulation mechanism of ADAR1-mediated RNA editing events in hematologic malignancies, and further discussed the medical potential and clinical application of ADAR1.
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Objective To observe the clinical efficacy of Modified Tongxie Yaofang(Important Formula for Relieving Diarrhea with Pain)in the treatment of patients with diarrhea-predominant irritable bowel syndrome(IBS-D)with liver-depression and spleen-deficiency syndrome.Methods Sixty patients with IBS-D of liver depression and spleen deficiency type were randomly divided into treatment group and control group,30 patients in each group.The patients in the treatment group were given modified Tongxie Yaofang,and the patients in the control group were given Pivacurium Bromide Tablets(Dicetel).Both groups were treated for a 4-week course of treatment.The changes of traditional Chinese medicine(TCM)syndrome scores,irritable bowel syndrome quality of life(IBS-QOL)scores,Hamilton Anxiety Scale(HAMA)scores of the two groups were observed before and after the treatment.Moreover,the efficacy for overall symptomatic improvement in the two groups was evaluated according to the grading of irritable bowel syndrome symptom severity score(IBS-SSS),and the efficacy for improving single symptom such as abdominal pain and diarrhea as well as the relapse after 4 weeks of drug cessation in the two groups were compared.Results(1)After 4 weeks of treatment,the total effective rate for overall symptomatic improvement in the treatment group was 83.33%(25/30),and that in the control group was 43.33%(13/30).The intergroup comparison(tested by chi-square test)showed that the efficacy for overall symptomatic improvement in the treatment group was significantly superior to that in the control group(P<0.01).(2)After 4 weeks of treatment,the total effective rate for improving single symptom of abdominal pain and diarrhea in the treatment group was 80.00%(24/30),90.00%(27/30),and that in the control group was 43.33%(13/30),46.67%(14/30),respectively.The intergroup comparison(tested by chi-square test)showed that the efficacy for improving single symptom of abdominal pain and diarrhea in the treatment group was significantly superior to that in the control group(P<0.01).(3)After 4 weeks of treatment,the TCM syndrome scores,IBS-QOL scores,and HAMA scores of patients in both groups were significantly decreased compared with those before treatment(P<0.05 or P<0.01),and the decrease in the treatment group was significantly superior to that in the control group(P<0.01).(4)After 4 weeks of drug withdrawal,the recurrence rate of the treatment group was 24.00%(6/25),which was significantly lower than that of the control group(61.54%,8/13),and the difference was statistically significant between the two groups(P<0.05).Conclusion Modified Tongxie Yaofang exerts certain effect in treating patients with IBS-D of liver depression and spleen deficiency type,and the decoction is effective on decreasing the scores of symptoms of abdominal pain and diarrhea as well as TCM syndrome scores,improving the quality of life of the patients,and alleviating the anxiety status of the patients.
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ObjectiveTo describe the epidemic characteristics of COVID-19 after policy adjustment from “Category B notifiable disease with category A management” to “Category B notifiable disease with category B management”, and to explore the protective effect of previous infection with SARS-CoV-2 on common symptoms of reinfection. MethodsHealthcare workers infected with SARS-CoV-2 in a grade A tertiary hospital in Shanghai were included in the study from December 4, 2022 to January 11, 2023. Data on demographic characteristics, clinical symptoms, medical history, and COVID-19 vaccination history were collected. We determined the epidemiological curve and characteristics, and then compared the difference in the severity of clinical symptoms between primary and reinfection subjects. ResultsA total of 2 704 cases were included in the study, of which 45 had reinfection, 605 (22.4%)were males, 608 (22.5%)were doctors, 1 275 (47.2%) were nurses, and 2 351 (86.9%) received ≥3 doses of COVID-19 vaccination. The average age of these healthcare workers was (34.9±9.1) years old. The number of cases with mild/moderate illness, asymptomatic infection, fever, headache, dry cough, expectoration, and chest tightness were 2 704 (100.0%), 92 (3.4%), 2 385 (88.2%), 2 066 (76.4%), 1 642 (60.7%), 1 807 (66.8%), and 439 (16.2%), respectively. Reinfection was a protective factor for fever (OR=0.161, P<0.001), headache (OR=0.320, P<0.001), and peak body temperature (β=-0.446, P<0.001). ConclusionFollowing the COVID-19 policy adjustment as a category B notifiable disease, healthcare workers at a grade A tertiary hospital in Shanghai predominantly experiences mild to moderate COVID-19 symptoms. Reinfection results in milder clinical manifestations, with a lower proportion of being asymptomatic.
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It has become an industry consensus that self-assembled nanoparticles (SAN) are formed by molecular recognition of chemical components in traditional Chinese medicine during the decoction process. The insoluble components in the decoction are mostly in the form of nanoparticles, which can improve the problem of poor water solubility. However, the transfer rate of these insoluble components in the decoction is still very low, which limits the efficacy of the drug. This study aimed to refine the traditional decoction self-assembly phenomenon. The self-assembled nanoparticles were constructed by micro-precipitation method (MP-SAN), and characterized by particle size, zeta potential, stability index and morphology. The formation of MP-SAN and alterations in related physicochemical properties were evaluated using modern spectroscopic and thermal analysis techniques. The quality value transmitting pattern of lignan components within the MP-SAN was assessed via high performance liquid chromatography (HPLC). The MP-SAN showed sphere-like structure with uniform morphology, particle size of (245.3 ± 3.2) nm, polydispersity index (PDI) of (0.13 ± 0.03), zeta potential of (-48.9 ± 5.9) mV and stability index (SI) of (86.05% ± 2.27%). Comprehensive analyses using ultraviolet visible spectroscopy, Fourier transform infrared spectroscopy, differential scanning calorimetry, and other techniques confirmed molecular recognition between the decoction and ethanol extraction, leading to electron rearrangement under the influence of non-covalent bonding. This resulted in the formation of nanoparticles possessing superior thermal stability. As determined by HPLC, the encapsulation rates of the index components in the MP-SAN were all greater than 75% (dehydrodiconiferyl alcohol: 77.00%; herpetolide A: 78.57%; herpetrione: 94.53%), and the transfer rates were all higher than 65% (dehydrodiconiferyl alcohol: 96.01%; herpetolide A: 67.86%; herpetrione: 65.55%), which were 1.34, 1.38 and 4.81 times compared with those of the traditional decoction. In summary, this study successfully constructed the MP-SAN based on micro-precipitation method to achieve high transfer rate and high encapsulation rate of insoluble components in docoction, which provides a pharmaceutics idea for the efficient utilization of pharmacodynamic substance basis of traditional Chinese medicine.
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Aim To screen and study the expression of long non-coding RNA (IncRNA) in rats with middle cerebral artery occlusion (MCAO) with MCAO treated with Tao Hong Si Wu decoction (THSWD) and determine the possible molecular mechanism of THSWD in treating MCAO rats. Methods Three cerebral hemisphere tissue were obtained from the control group, MCAO group and MCAO + THSWD group. RNA sequencing technology was used to identify IncRNA gene expression in the three groups. THSWD-regulated IncRNA genes were identified, and then a THSWD-regu-lated IncRNA-mRNA network was constructed. MCODE plug-in units were used to identify the modules of IncRNA-mRNA networks. Gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) were used to analyze the enriched biological functions and signaling pathways. Cis- and trans-regulatory genes for THSWD-regulated IncRNAs were identified. Reverse transcription real-time quantitative pol-ymerase chain reaction (RT-qPCR) was used to verify IncRNAs. Molecular docking was used to identify IncRNA-mRNA network targets and pathway-associated proteins. Results In MCAO rats, THSWD regulated a total of 302 IncRNAs. Bioinformatics analysis suggested that some core IncRNAs might play an important role in the treatment of MCAO rats with THSWD, and we further found that THSWD might also treat MCAO rats through multiple pathways such as IncRNA-mRNA network and network-enriched complement and coagulation cascades. The results of molecular docking showed that the active compounds gallic acid and a-mygdalin of THSWD had a certain binding ability to protein targets. Conclusions THSWD can protect the brain injury of MCAO rats through IncRNA, which may provide new insights for the treatment of ischemic stroke with THSWD.
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Objective:To investigate the effects of 3 adhesives on the bond force and durability of polished and glazed zirconia ceram-ics to orthodontic metal brackets respectively.Methods:Universal adhesives,Single Bond Universal(SBU)and Prime&Bond Universal(PBU)were respectively used to bond polished and glazed zirconia to metal braces of maxillary central incisors using TransbondTM MIP(TM)as the control.The shear bond strength(SBS),the fracture morphology and adhesive residual index(ARI)were examed after wa-ter bath or water bath-thermal cycling storage.Results:The adhesive(P<0.001)and storage conditions(P<0.001)significantly af-fected the shear bond strength of zirconia to brackets.There was no significant difference between the polished or glazed groups(P=0.09).SBU showed the stronger SBS and lower ABI,there were significant differences in ARI scores among the 3 cements(P<0.001).Conclusion:SBU may have better bonding performance than PBU and TM in the orthodontic bonding of polished or glazed zir-conia surfaces to the zirconia ceramics.
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Objective:To report a Chinese pedigree with autosomal dominant Waardenburg syndrome, and to identify causative gene mutations.Methods:Clinical data and peripheral blood samples were collected from the proband and her parents. Genomic DNA was extracted, gene mutations were detected through a next-generation skin-targeted sequencing panel, and Sanger sequencing was performed to verify causative mutations.Results:The proband clinically presented with irregular white patches on the abdomen and lower limbs, moderate to severe sensorineural deafness in the right ear, and iris heterochromia in both eyes. The proband′s mother presented with iris heterochromia in both eyes, epicanthus, early canities and thick eyebrows. In the family, both the proband and her mother were diagnosed with Waardenburg syndrome. A causative frameshift mutation c.976-977delinsT (p.Thr327Profs*54) was identified in both the proband and her mother, which caused the AG to TT base substitution at positions 976 - 977 in the coding region of exon 7 of the PAX3 gene, resulted in a frameshift from the amino acid position 327 to 54 in the PAX3 protein (threonine was substituted by proline at amino acid position 327). The proband′s father showed a normal phenotype, and his genetic test results were negative.Conclusion:The novel frameshift mutation c.976-977delinsT (p.Thr327Profs*54) in the PAX3 gene may contribute to the clinical phenotype of the patients with Waardenburg syndrome in the family.
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ObjectiveTo observe the efficacy and safety of Tongguan Capsule(通冠胶囊)on ventricular remodeling in patients after acute myocardial infarction (AMI), and to explore the possible mechanism. MethodsA total of 53 ST-segment elevation myocardial infarction (STEMI) patients were collected and randomly divided into 26 cases in the treatment group and 27 cases in the control group. The control group was given conventional therapy after percutaneous coronary intervention (PCI) for AMI, and the treatment group was given Tongguan Capsules (4.5 g each time, 3 times a day) on the basis of the control group. The course of treatment was 12 weeks. Echocardiographic data and stool samples were collected from subjects before and after the intervention, and left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVi), left ventricular end-systolic volume index (LVESVi), left ventricular mass index (LVMi) were measured and calculated, so as to compare the number of cases of left ventricular remodeling in the two groups. At the same time, 16S rDNA sequencing was performed on the stool samples to analyze the diversity of gut microbiota (GM), the composition of the GM, the GM difference between the groups; recording the incidence of major adverse cardiovascular events (MACEs) and adverse reactions of patients in the two groups during the study period; and performing Spearman's correlation analyses of the post-treatment flora data with LVEF, LVEDVi, LVESVi, LVM, and LVMi in the two groups. ResultsOne case fail to follow up in the treatment group and 2 cases fail to follow up in the control group, and 25 cases in each of the two groups were finally included in the analysis. LVEDVi, LVESVi, and LVMi of the control group after treatment were higher than those before treatment (P<0.05); after treatment, LVEDVi, LVESVi and LVMi in the treatment group were lower than those in the control group (P<0.05). Left ventricular remodeling occurred in 5 cases (20.00%) in the treatment group and 13 cases (52.00%) in the control group, and the incidence of left ventricular remodeling in the treatment group was lower than that in the control group (P=0.03). After treatment, the ACE estimation and Chao estimation of bacterial abundance in the treatment group were higher than that before treatment and that in the control group (P<0.05). The treatment group showed an increase in Mycobacterium anisopliae phylum and a decrease in Mycobacterium thickum, Mycobacterium anisopliae phylum, and Mycobacterium patella phylum after treatment (P<0.05). When comparing between groups after treatment, the relative abundance of Prevotella, Agathobacter, Dialister, Eubacterium coprostanoligenes group was up-reuglated and the relative abundance of Enterococcus was down-regulated in the treatment group(P<0.05 or P<0.01). There was no statistically significant difference in the incidence of MACEs and the occurrence of adverse reactions between groups during treatment (P>0.05). The results of correlation analysis showed that Prevotella were positively correlated with LVEF and negatively correlated with LVEDVi, LVESVi, LVM, and LVMi (P<0.01). Agathobacter group were negatively correlated with LVEDVi, LVESVi (P<0.01); Enterococcus group were positively correlated with LVESVi (P<0.05). ConclusionTongguan Capsules can improve ventricular remodeling in patients with acute ST-segment elevation myocardial infarction with better safety; its mechanism may be related to adjusting the enrichment of related bacteria such as Prevotella, Dialister and Enterococcus and other related bacterial genera, increasing the colonization and diversity of beneficial bacteria, and adjusting the structure of GM.
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Breast cancer has become the most prevalent malignant tumor among women, putting the health of women at serious risk. Screening for lead compounds in the active ingredients of plant that are effective and less toxic continues to be an important strategy for treating breast cancer. Gerbeloid J, a coumarin isolated from Gerbera piloselloides (L.) Cass., showed significant anti-cancer activity. But there is no report on the effect and mechanism of gerbeloid J on cycle and apoptosis of breast cancer. By using the CCK-8, clone formation, and PI staining assays, the effects of gerbeloid J on the proliferation of MCF-7 and MDA-MB-231 cells were assessed in this study. The effects of gerbeloid J on the apoptosis and mitochondrial function of MCF-7 and MDA-MB-231 cells were assessed using DAPI, Annexin V/TO-PRO-3, Rhod-2 AM, TMRM, DCFDA staining assays, and Western blot. The results demonstrated that gerbeloid J regulated the P21/CDC25C/CDK-1/cyclin B1 pathway and arrested the cell cycle at G2/M phase to suppressed the proliferation of MCF-7 and MDA-MB-231 cells. Additionally, gerbeloid J induced apoptosis through the stimulation of mitochondrial calcium excess, reduction of mitochondrial membrane potential, and promotion of ROS generation, and its mechanism was related to the activation of mitochondrial apoptotic pathway. In conclusion, by regulating the P21/CDC25C/CDK-1/cyclin B1 pathway and activating the mitochondrial apoptosis pathway, gerbeloid J could cause breast cancer cell cycle arrest and apoptosis, which might offer a promising candidate for the creation of new drugs against breast cancer.
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Objective: Bioinformatics analysis was used to screen differentially expressed genes (DEGs) in macrophages of sepsis myocardial injury and to verify key genes. Methods: Experiment 1 (gene chip and bioinformatics analysis): The gene chip data GSE104342 of cardiac macrophages in septic mice was downloaded from Gene Expression Omnibus database. DEGs were obtained by R language analysis. DAVID online database was used to obtain gene ontology and kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis of DEGs. STRING online database was used for protein-protein interaction network analysis of DEGs, and then key genes were screened by using Cytoscape software and molecular complex detection (MCODE) plug-ins. Experiment 2 (sepsis model construction and related protein verification): Ten male C57BL/6 mice, aged 8-14 weeks. Five mice were randomly selected as control group, and 5 mice were selected as the sepsis group by building a mice sepsis model in vivo. Echocardiography was used to detect the cardiac function. Hematoxylin-eosin staining was used to assess the cardiac morphology. TUNEL staining was used to evaluate cardiomyocyte apoptosis. Immunofluorescence staining was used to detect the expression of differentiation antigen cluster 206 (CD206),inducible nitric oxide synthases (iNOS),F4/80,suppressor of cytokine signaling 3 (Socs3) ,interleukin 1 receptor antagonist (Il1rn) and chemokine C-C motif ligand 7 (Ccl7) protein. RAW264.7 macrophages were cultured in vitro and divided into 2 groups: LPS groupstimulated by lipopolysaccharide (LPS, 1 mg/L) and blank control group treated with equal-volume phosphate buffer solution. Reverse transcription-polymerase chain reaction (RT-PCR) was used to evaluate the expression of Socs3, Il1rn and Ccl7 in vitro. Results: Experiment 1: 24 647 genes were screened in GSE104342 dataset and 177 genes (0.72%) were differential expression, including 120 up-regulated genes and 57 down-regulated genes. Gene ontology enrichment analysis showed that DEGs were mainly involved in inflammatory response, immune response, apoptosis regulation and antigen processing and presentation. KEGG signaling pathway analysis showed that DEGs in cardiac macrophages of septic mice were mainly enriched in cytokine-cytokine receptor interaction, tumor necrosis factor signaling pathway, NOD like receptor signaling pathway. Three hub genes were obtained by STRING and Cytoscape analysis, including Socs3, Il1rn and Ccl7. Experiment 2: In vivo, it was found that compared with the control group, the cardiac function of the sepsis mice decreased significantly, the myocardial cells were significantly edema, inflammatory cell infiltration, myocardial fiber rupture, some myocardial nuclei dissolved and disappeared, and the cardiomyocyte apoptosis increased, suggesting that the sepsis myocardial injury model of mice was successfully constructed. Compared with the control group, the expression of CD206 in the myocardium of septic mice was down-regulated, the expression of iNOS, F4/80, Socs3, Il1rn and Ccl7 were up-regulated. In addition, there was co-localization between Socs3, Il1rn, Ccl7 and F4/80 protein. Compared with the blank control group, the expression of Socs3, Il1rn and Ccl7 significantly upregulated after LPS intervention in vitro by RT-PCR. Conclusions: The selected key genes Socs3, Il1rn and Ccl7 were up-regulated in myocardial macrophages of septic mice. Socs3, Il1rn and Ccl7 are expected to become new targets for the diagnosis and treatment of sepsis cardiac injury.
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Male , Mice , Animals , Lipopolysaccharides , Mice, Inbred C57BL , Myocardium , Computational Biology , Sepsis , Macrophages , Cytokines , Gene Expression ProfilingABSTRACT
Health damage including chronic disease caused by air pollution have attracted increasing attention. With the acceleration of industrialization and urbanization, the emission of air pollutants has increased, and its association with chronic diseases has become a research trending topic. Cardiovascular disease, cancer, diabetes, and chronic respiratory disease are the major chronic diseases, causing about 86.6% of the total deaths in China. The prevention and control of chronic diseases, especially the etiologic prevention, is a major public health issue related to national health. This article summarizes the recent progress in research of association of indoor and outdoor air pollution with all-cause mortality, the deaths and disease burden of four major chronic diseases, i.e. cardiovascular disease, cancer, diabetes, and chronic respiratory disease, and puts forward suggestions for the reduction of the burden caused by chronic diseases due to air pollution to provide a theoretical foundation to revise air quality standards in China.
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Humans , Cardiovascular Diseases , Air Pollution , China , Cost of Illness , Chronic Disease , Respiratory Tract DiseasesABSTRACT
Objective To explore the expression of PD-1 and CTLA-4 in osteosarcoma and their clinical significance. Methods Fifty-eight cases of osteosarcoma encountered from 2007 to 2016 were enrolled. The expression levels of PD-1 and CTLA-4 were detected through immunohistochemistry (EnVision method). Results PD-1 was positively expressed in 31 (53.4%) cases and negatively expressed in 27 (46.6%) cases. CTLA-4 was positively expressed in 19 (32.8%) cases and negatively expressed in 39 (67.2%) cases. A total of 12 (20.7%) cases were PD-1 and CTLA-4 double positive, whereas 20 (34.5%) cases were double negative, and 26 (44.8%) cases were single positive. The positive expression of PD-1 was correlated with neoadjuvant chemotherapy, tumor metastasis and relapse, and shortened survival time (P < 0.05). The positive expression of CTLA-4 was partly related with late Ennecking stage (P=0.051). Double positive expression was related to the highest tumor metastasis and relapse rates and the worst prognosis (P < 0.05), compared with double negative and single positive expression. Conclusion Positive expression of PD-1 and CTLA-4 in osteosarcoma is associated with worse prognosis, whereas double positive expression is associated with the highest tumor relapse and metastasis rates and shortest survival time. These results are potential valuable references for osteosarcoma immunotherapy.
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Polymyxin antibiotics,particularly polymyxin B and polymyxin E(colistin),are often considered a last line of defense against penicillin carbapenem-resistant Enterobacteriaceae(CRE),because of their favorable clinical antibacterial effects.However,the emergence and spread of plasmid-mediated colistin resistance genes(mcr),and their multiple isoforms,have posed a substantial threat to public health in recent years.The mcr-1 genes exhibit complexity in both host and transmis-sion routes,and diversity in both the genetic environment and ecological locus distribution.Herein,we discuss the prevalence,transmission routes,drug resistance and transmission mechanisms of mcr-1 positive isolates,on the basis of epidemiological studies of Enterobacteriaceae carrying mcr-1 worldwide.to provide a theoretical reference for researchers.
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IgA-dominant infection-related glomerulonephritis (IgA-IRGN) is a unique form of infection-associated glomerulonephritis. The main causative organism is staphylococcus. Although IgA-IRGN is rare in children, the prevalence is gradually increasing, and the prognosis is poor in children with immunodeficiency and mucocutaneous barrier dysfunction. The clinical manifestations are varying degrees of hematuria, proteinuria, acute kidney injury and hypocomplementemia. The renal pathology is similar to postinfectious glomerulonephritis, therefore differential diagnosis is challenging. The paper reviews the current research progress of IgA-IRGN to improve the pediatrician's understanding of IgA-IRGN in children and avoid misdiagnosis.
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BACKGROUND@#The benefits of healthy lifestyles are well recognized. However, the extent to which improving unhealthy lifestyles reduces cardiovascular disease (CVD) risk needs to be discussed. We evaluated the impact of lifestyle improvement on CVD incidence using data from the China-PAR project (Prediction for Atherosclerotic Cardiovascular Disease Risk in China).@*METHODS@#A total of 12,588 participants free of CVD were followed up for three visits after the baseline examination. Changes in four lifestyle factors (LFs) (smoking, diet, physical activity, and alcohol consumption) were assessed through questionnaires from the baseline to the first follow-up visit. Cox proportional hazard models were used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs). The risk advancement periods (RAPs: the age difference between exposed and unexposed participants reaching the same incident CVD risk) and population-attributable risk percentage (PAR%) were also calculated.@*RESULTS@#A total of 909 incident CVD cases occurred over a median follow-up of 11.14 years. Compared with maintaining 0-1 healthy LFs, maintaining 3-4 healthy LFs was associated with a 40% risk reduction of incident CVD (HR = 0.60, 95% CI: 0.45-0.79) and delayed CVD risk by 6.31 years (RAP: -6.31 [-9.92, -2.70] years). The PAR% of maintaining 3-4 unhealthy LFs was 22.0% compared to maintaining 0-1 unhealthy LFs. Besides, compared with maintaining two healthy LFs, improving healthy LFs from 2 to 3-4 was associated with a 23% lower risk of CVD (HR = 0.77, 95% CI: 0.60-0.98).@*CONCLUSIONS@#Long-term sustenance of healthy lifestyles or improving unhealthy lifestyles can reduce and delay CVD risk.
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For the first time, this study evaluated the gender differences and mechanisms of the antidepressant effects of raw Rehmanniae Radix(RRR) based on the classic depression model with traditional Chinese medicine syndrome of Yin deficiency and internal heat. The depression model with Yin deficiency and internal heat was established by the widely recognized and applied method of thyroxine induction of the classic depression model with Yin deficiency and internal heat(chronic unpredictable mild stress). Male and female mice were simultaneously treated with RRR. The study analyzed indicators of nourishing Yin and clearing heat, conventional antidepressant efficacy test indicators, and important biomolecules reflecting the pathogenesis and prevention and treatment mechanisms of depression, and conducted a correlation analysis of antidepressant efficacy, Yin-nourishing and heat-clearing efficacy, and biological mechanism in different genders, thereby comprehensively assessing the antidepressant effects of RRR on depression of Yin deficiency and internal heat, as well as its gender differences and mechanisms. RRR exhibited antidepressant effects in both male and female mouse models, and its antidepressant efficacy showed gender differences, with a superior effect observed in females. Moreover, the effects of RRR on enhancing or improving hippocampal neuronal pathology, nucleus-positive areas, postsynaptic dense area protein 95, and synaptophysin protein expression were more significant in females than in males. In addition, RRR significantly reversed the abnormal upregulation of nuclear factor(NF)-κB/cyclooxygenase 2(COX2)/NOD-like receptor thermal protein domain associated protein 3(NLRP3) pathway proteins in the hippocampus of both male and female mouse models. The antidepressant effects of RRR were more pronounced in depression female mice with Yin deficiency and internal heat syndrome, possibly due to the improvement of neuronal damage and enhancement of neuroplasticity. The antidepressant mechanisms of RRR for depression with Yin deficiency and internal heat syndrome may be associated with the downregulation of the NF-κB/COX2/NLRP3 pathway to reduce neuronal damage and enhance neuroplasticity.
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Male , Female , Mice , Animals , Yin Deficiency , NLR Family, Pyrin Domain-Containing 3 Protein , Sex Factors , Cyclooxygenase 2 , NF-kappa B , Antidepressive Agents/pharmacologyABSTRACT
Objective: To observe the effect of platelets on hematopoietic stem cell (HSCs) implantation in mice with radiation-induced bone marrow injury and bone marrow transplantation models. Methods: ①Male C57BL/6 mice were divided into a single irradiation group and a radiation infusion group after receiving (60)Co semimyeloablative irradiation for 18-10 weeks. The irradiation infusion group received 1×10(8) platelets expressing GFP fluorescent protein. ② The allogeneic bone marrow transplantation model was established. The experimental groups included the simple transplantation group (BMT) and the transplantation infusion group (BMT+PLT). The BMT group was infused through the tail vein only 5 × 10(6) bone marrow cells, the BMT+PLT group needs to be infused with bone marrow cells at the same time 1× 10(8) platelets. ③ Test indicators included peripheral blood cell and bone marrow cell counts, flow cytometry to detect the proportion of hematopoietic stem cell (HSC) and hematopoietic progenitor cells, bone marrow cell proliferation and apoptosis, and pathological observation of vascular niche damage and repair. Results: ①On the 3rd, 7th, 14(th), and 21st days after irradiation, the bone marrow cell count of the infusion group was higher than that in the single irradiation group (P<0.05), and the peripheral blood cell count was also higher. A statistically significant difference was found between the white blood cell count on the 21st day and the platelet count on the 7th day (P<0.05). In the observation cycle, the percentage of bone marrow cell proliferation in the infusion group was higher, while the percentage of apoptosis was lower. ② The results of bone tissue immunofluorescence after irradiation showed that the continuity of hematopoietic niche with red fluorescence was better in the irradiation infusion group. ③The chimerism percentage in the BMT+PLT group was always higher than that in the BMT group after transplantation.④ The BMT+PLT group had higher bone marrow cell count and percentage of bone marrow cell proliferation on the 7th and 28th day after transplantation than that in the BMT group, and the percentage of bone marrow cell apoptosis on the 14th day was lower than that in the BMT group (P<0.05). After the 14th day, the percentage of stem progenitor cells in the bone marrow cells of mice was higher than that in the BMT group (P<0.05). ⑤The immunohistochemical results of bone marrow tissue showed that the continuity of vascular endothelium in the BMT+PLT group was better than that in the BMT group. Conclusion: Platelet transfusion can alleviate the injury of vascular niche, promotes HSC homing, and is beneficial to hematopoietic reconstruction.
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Mice , Animals , Bone Marrow Transplantation , Bone Marrow , Mice, Inbred C57BL , Hematopoietic Stem Cells , Bone Marrow Diseases , Hematopoietic Stem Cell Transplantation , Mice, Inbred BALB CABSTRACT
Aim To study the apoptosis of human hep-atoma cell line ( HepG2 ) induced by different polar parts of Arnebia euchroma ( Royle ) Johnst ( AE ) and to verify its anti-hepatoma effect by a mouse orthotopic liver cancer model so as to explore the anti-cancer effect of AE extract. Methods Firstly, MTT method and Annexin V-FITC/PI double staining method were used to detect the anti-proliferative and pro-apoptotic effects of each polar part of AE on HepG2 cells, and Western blot was used to detect the expression of Bcl-2 apoptosis family proteins incells. Based on the above experimental results, the effective parts with significant pro-apoptotic effect were screened out for anti-in situ liver cancer experiments in mice, and the organ indexes, liver function indexes and tissue sections of mice with orthotopic liver cancer before and after administration were evaluated. Results With the decrease of the polarity of AE extract,the anti-proliferation and pro-apoptotic effects on HepG2 cells were enhanced, and the anti-proliferation and apoptosis-inducing effects of AE petroleum ether fraction ( AEP) were the most significant. When AEP dose was 1.56 (μg • L
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This study explored toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction for the first time, and further explored its detoxification mechanism. Nine processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction were prepared by orthogonal experiment with three factors and three levels. Based on the decrease in the content of the main hepatotoxic component diosbulbin B before and after processing of Rhizoma Dioscoreae Bulbiferae by high-performance liquid chromatography, the toxicity attenuation technology was preliminarily screened out. On this basis, the raw and representative processed products of Rhizoma Dioscoreae Bulbiferae were given to mice by gavage with 2 g·kg~(-1)(equival to clinical equivalent dose) for 21 d. The serum and liver tissues were collected after the last administration for 24 h. The serum biochemical indexes reflecting liver function and liver histopathology were combined to further screen out and verify the proces-sing technology. Then, the lipid peroxidation and antioxidant indexes of liver tissue were detected by kit method, and the expressions of NADPH quinone oxidoreductase 1(NQO1) and glutamate-cysteine ligase(GCLM) in mice liver were detected by Western blot to further explore detoxification mechanism. The results showed that the processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reduced the content of diosbulbin B and improved the liver injury induced by Rhizoma Dioscoreae Bul-biferae to varying degrees, and the processing technology of A_2B_2C_3 reduced the excessive levels of alanine transaminase(ALT) and aspartate transaminase(AST) induced by raw Rhizoma Dioscoreae Bulbiferae by 50.2% and 42.4%, respectively(P<0.01, P<0.01). The processed products of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction reversed the decrease protein expression levels of NQO1 and GCLM in the liver of mice induced by raw Rhizoma Dioscoreae Bulbiferae to varying degrees(P<0.05 or P<0.01), and it also reversed the increasing level of malondialdehyde(MDA) and the decreasing levels of glutathione(GSH), glutathione peroxidase(GPX), and glutathione S-transferase(GST) in the liver of mice(P<0.05 or P<0.01). In summary, this study shows that the optimal toxicity attenuation processing technology of Rhizoma Dioscoreae Bulbiferae stir-fried with Paeoniae Radix Alba decoction is A_2B_2C_3, that is, 10% of Paeoniae Radix Alba decoction is used for moistening Rhizoma Dioscoreae Bulbiferae and processed at 130 ℃ for 11 min. The detoxification mechanism involves enhancing the expression levels of NQO1 and GCLM antio-xidant proteins and related antioxidant enzymes in the liver.
Subject(s)
Mice , Animals , Antioxidants/analysis , Plant Extracts/pharmacology , Drugs, Chinese Herbal/chemistry , Rhizome/chemistry , Paeonia/chemistry , Glutathione/analysisABSTRACT
This study aims to separate and characterize self-assembled nanoparticles(SAN) from Shaoyao Gancao Decoction(SGD) and determine the content of active compounds. Further, we aimed to observe the therapeutic effect of SGD-SAN on imiquimod-induced psoriasis in mice. The separation of SGD was performed by dialysis, and the separation process was optimized by single factor experiment. The SGD-SAN isolated under the optimal process was characterized, and the content of gallic acid, albiflorin, paeoniflorin, liquiritin, isoliquiritin apioside, isoliquiritin, and glycyrrhizic acid in each part of SGD was determined by HPLC. In the animal experiment, mice were assigned into a normal group, a model group, a methotrexate group(0.001 g·kg~(-1)), and SGD, SGD sediment, SGD dialysate, and SGD-SAN groups of different doses(1, 2, and 4 g·kg~(-1)) respectively. The psoriasis grade of mice was evaluated based on the pathological changes of skin lesions, the content of inflammatory cytokines, organ index and other indicators. The results showed that SAN obtained by centrifugation at 13 000 r·min~(-1) for 30 min was stable after dialysis for 4 times, which were uniform spherical nanoparticles with the particle size of(164.43±1.34) nm, the polydispersity index of(0.28±0.05), and the Zeta potential of(-12.35±0.80) mV. The active compound content accounted for more than 70% of SGD. Compared with the model group, SAN and SGD decreased the skin lesion score, spleen index, and inflammatory cytokine levels(P<0.05 or P<0.01) and alleviated the skin thickening and infiltration of inflammatory cells. However, the sediment group and the dialysate group had no obvious effect. SGD showed a good therapeutic effect on imiquimod-induced psoriasis in mice, and SAN demonstrated the effect equivalent to SGD in a dose-dependent manner. Therefore, we conclude that the SAN formed during decocting is the main active form of SGD, which can lower the levels of inflammatory cytokines, promote the normal differentiation of keratinocytes, and reduce the infiltration of inflammatory cells in the treatment of psoriasis lesions in mice.