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MOF-808, owing to the synergistic effect of its large surface area and surface charge matching, showed a diclofenac sodium (DCF) removal capacity as high as 630 mg g-1, and the ability to adsorb 436 mg g-1 DCF in two hours, outperforming many common Zr-MOFs under the same conditions. Importantly, a series of free-standing mixed-matrix membranes made by combining polyacrylonitrile with MOF-808 were fabricated and exhibited high efficiency of removing DCF from water via an easily accessible filtration method.
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ObjectiveTo investigate the effects of probiotics combined with bismuth quadruple therapy (BQT) on clinical efficacy、gastrointestinal adverse reactions and intestinal flora in Helicobacter pylori (HP) positive patients. MethodsThe patients who were positive for HP from May 2023 to July 2023 in the department of gastroenterology of Shanghai first people's hospital were randomly divided into2 groups with 40 people in each group. The probiotic group was given 2 weeks of quadruple therapy with probiotics and standard BQT, followed by 4 weeks of oral probiotics after quadruple discontinuation. The placebo group was given 2 weeks of probiotic placebo and standard BQT, followed by 4 weeks of oral probiotic placebo. 13C urea breath test was used to evaluate the clinical efficacy, gastrointestinal symptoms rating Scale was used to evaluate the gastrointestinal adverse reactions of patients before and after the intervention, and microbial diversity 16S rDNA sequencing technology was used to detect the level of intestinal flora of patients before and after the intervention. ResultsThere was no significant difference in the eradication rate between the two groups (P>0.05). Before the intervention, there was no significant difference in the scores of the gastrointestinal symptom rating scale between the probiotic group and the placebo group. After the intervention, patients in the probiotic group had significantly lower pain scores on acid reflux (1.10±0.30 vs 1.35±0.53, P<0.05) and stomach or abdominal hunger than in the placebo group (1.07±0.26 vs 1.30±0.52, P<0.05). Through the before-and-after comparison of the probiotic group, the scores of abdominal pain (1.24±0.44 vs 1.58±0.71, P<0.05), stomach or abdominal hunger (1.07±0.26 vs 1.27±0.45, P<0.05) and dry and hard stool (1.24±0.49 vs 1.48±0.75,P<0.05) were significantly lower in the probiotic group than before the intervention in the probiotic group. ConclusionProbiotics combined with BQT can improve the gastrointestinal adverse reactions and intestinal flora disorders in the process of quadruple drug therapy, but it does not improve the eradication rate of HP.
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Polymorphs of ZnHPO3·2H2O with centrosymmetry (Cmcm) and noncentrosymmetry (C2) structures were prepared by modified solution evaporation and seed-crystal-induced secondary nucleation methods. In Cmcm-ZnHPO3·2H2O, the zinc atoms are only octahedrally coordinated, while in C2-ZnHPO3·2H2O, they feature both tetrahedral and octahedral coordination. As a result, Cmcm-ZnHPO3·2H2O features a 2D layered structure with lattice water molecules located in the interlayer space, while C2-ZnHPO3·2H2O features a 3D electroneutral framework of tfa topology connected by Zn(1)O4, Zn(2)O6, and HPO3 units. The UV-visible diffuse reflectance spectra associated with Tauc's analyses give a direct bandgap of 4.24 and 4.33 eV for Cmcm-ZnHPO3·2H2O and C2-ZnHPO3·2H2O, respectively. Moreover, C2-ZnHPO3·2H2O exhibits a weak second harmonic generation (SHG) response and a moderate birefringence for phase matching, indicating its potential as a nonlinear optical material. Detailed dipole moment calculation and analysis confirmed that the SHG response mainly derived from the HPO3 pseudo-tetrahedra.
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OBJECTIVES@#To investigate the distribution characteristics and correlation of intestinal and pharyngeal microbiota in early neonates.@*METHODS@#Full-term healthy neonates who were born in Shanghai Pudong New Area Maternal and Child Health Hospital from September 2021 to January 2022 and were given mixed feeding were enrolled. The 16S rRNA sequencing technique was used to analyze the stool and pharyngeal swab samples collected on the day of birth and days 5-7 after birth, and the composition and function of intestinal and pharyngeal microbiota were analyzed and compared.@*RESULTS@#The diversity analysis showed that the diversity of pharyngeal microbiota was higher than that of intestinal microbiota in early neonates, but the difference was not statistically significant (P>0.05). On the day of birth, the relative abundance of Proteobacteria in the intestine was significantly higher than that in the pharynx (P<0.05). On days 5-7 after birth, the relative abundance of Actinobacteria and Proteobacteria in the intestine was significantly higher than that in the pharynx (P<0.05), and the relative abundance of Firmicutes in the intestine was significantly lower than that in the pharynx (P<0.05). At the genus level, there was no significant difference in the composition of dominant bacteria between the intestine and the pharynx on the day of birth (P>0.05), while on days 5-7 after birth, there were significant differences in the symbiotic bacteria of Streptococcus, Staphylococcus, Rothia, Bifidobacterium, and Escherichia-Shigella between the intestine and the pharynx (P<0.05). The analysis based on the database of Clusters of Orthologous Groups of proteins showed that pharyngeal microbiota was more concentrated on chromatin structure and dynamics and cytoskeleton, while intestinal microbiota was more abundant in RNA processing and modification, energy production and conversion, amino acid transport and metabolism, carbohydrate transport and metabolism, coenzyme transport and metabolism, and others (P<0.05). The Kyoto Encyclopedia of Genes and Genomes analysis showed that compared with pharyngeal microbiota, intestinal microbiota was more predictive of cell motility, cellular processes and signal transduction, endocrine system, excretory system, immune system, metabolic diseases, nervous system, and transcription parameters (P<0.05).@*CONCLUSIONS@#The composition and diversity of intestinal and pharyngeal microbiota of neonates are not significantly different at birth. The microbiota of these two ecological niches begin to differentiate and gradually exhibit distinct functions over time.
Subject(s)
Humans , Infant, Newborn , Bacteria , China , High-Throughput Nucleotide Sequencing , Intestines , Microbiota , Pharynx/microbiology , RNA, Ribosomal, 16S/geneticsABSTRACT
OBJECTIVE: To screen differentially expressed gene (DEG) related to myelodysplastic syndrome (MDS) based on Gene Expression Omnibus (GEO) database, and explore the core genes and pathogenesis of MDS by analyzing the biological functions and related signaling pathways of DEG. METHODS: The expression profiles of GSE4619, GSE19429, GSE58831 including MDS patients and normal controls were downloaded from GEO database. The gene expression analysis tool (GEO2R) of GEO database was used to screen DEG according to | log FC (fold change) |≥1 and P<0.01. David online database was used to annotate gene ontology function (GO). Metascape online database was used to enrich and analyze differential genes in Kyoto Encyclopedia of Genes and Genomes (KEGG). The protein-protein interaction network (PPI) was constructed by using STRING database. CytoHubba and Mcode plug-ins of Cytoscape were used to analyze the key gene clusters and hub genes. R language was used to diagnose hub genes and draw the ROC curve. GSEA enrichment analysis was performed on GSE19429 according to the expression of LEF1. RESULTS: A total of 74 co-DEG were identified, including 14 up-regulated genes and 60 down regulated genes. GO enrichment analysis indicated that BP of down regulated genes was mainly enriched in the transcription and regulation of RNA polymerase II promoter, negative regulation of cell proliferation, and immune response. CC of down regulated genes was mainly enriched in the nucleus, transcription factor complexes, and adhesion spots. MF was mainly enriched in protein binding, DNA binding, and ß-catenin binding. KEGG pathway was enriched in primary immunodeficiency, Hippo signaling pathway, cAMP signaling pathway, transcriptional mis-regulation in cancer and hematopoietic cell lineage. BP of up-regulated genes was mainly enriched in type I interferon signaling pathway and viral response. CC was mainly enriched in cytoplasm. MF was mainly enriched in RNA binding. Ten hub genes and three important gene clusters were screened by STRING database and Cytoscape software. The functions of the three key gene clusters were closely related to immune regulation. ROC analysis showed that the hub genes had a good diagnostic significance for MDS. GSEA analysis indicated that LEF1 may affect the normal function of hematopoietic stem cells by regulating inflammatory reaction, which further revealed the pathogenesis of MDS. CONCLUSION: Bioinformatics can effectively screen the core genes and key signaling pathways of MDS, which provides a new strategy for the diagnosis and treatment of MDS.
Subject(s)
Computational Biology , Myelodysplastic Syndromes , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Gene Ontology , Humans , Myelodysplastic Syndromes/geneticsABSTRACT
This study aims to identify research trends of scaffolding in the field of science education. To this end, both descriptive analysis and co-word analysis were conducted to examine the selected articles published in the Social Science Citation Index journals from 2000 to 2019. A total of 637 papers were retrieved as research samples through rounds of searching in Web of Science database. Overall, this study reveals a growing trend of science educators' academic publications about scaffolding in the recent two decades. In these sample papers, from 1,487 non-repeated keywords, we extracted 286 author-defined keywords shared by at least two studies as a benchmark dictionary. A series of co-word analyses were then conducted based on the dictionary to reveal the underlying co-occurring relationships of the words in title and abstract of the sample papers. Results showed that "scaffolding," "support," and "design" were the top three most frequently used keywords during 2000 and 2019. Visualization of co-word networks in each 5-year period further helps clarify both educators' common research foci and relevant research trends. Derived discussion and potential research directions are also provided.
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CXC chemokine ligand 8 (CXCL8) is highly expressed in many human tumors including colorectal cancer, and it can promote the malignant progression of tumors. It was reported that M2 macrophages were abundant in colorectal cancer microenvironment, but whether CXCL8 affects the infiltration of M2 macrophages and its potential mechanism are not yet clear. The study aimed to investigate the effect of CXCL8 on M2 macrophage infiltration and chemotaxis in the colorectal cancer. Firstly, we analyzed the CXCL8 expression and immune cell infiltration in human colorectal cancer tissues from TCGA RNA-seq data. The expression of CXCL8 was verified by immunohistochemistry in tissues obtained from Shanxi Provincial Cancer Hospital. Then, Western blot and qRT-PCR were employed to detect CXCL8 expression in five colorectal cancer cell lines. THP-1 cells were allowed to differentiate into M2 macrophages via the phorbol myristate acetate (PMA) and IL-4 treatment, followed by detection of the chemotaxis of M2 macrophages towards HCT116, SW480 and CXCL8-HCT116, CXCL8-SW480 cell lines. HCT116 and SW480 cells were treated with interleukin 1β (IL-1β) to detect the expression of CXCL8, and co-cultured with M2 macrophages to analyze the chemotactic activity. The results revealed that the expression of CXCL8 was increased in pairs of CRC tissues versus normal adjacent tissues, and there were more M2 macrophage infiltration in cancer tissues with high expression of CXCL8. The mRNA and protein expression of CXCL8 in HCT116 and SW480 were increased after the IL-1β treatment (P < 0. 05). We confirmed that CXCL8 is a chemotactic factor for M2 macrophages by transwell assays (P<0. 05). In conclusion, CXCL8 in colorectal cancer cells can be induced by IL-1β in colorectal cancer cells and the upregulation of CXCL8 can promote the chemotaxis of M2 macrophages. The massive infiltration of M2 macrophages in colorectal cancer microenvironment may be related with the increased expression of CXCL8.
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Objective:To evaluate the efficacy and tolerability of the dual therapy of dolutegravir (DTG) plus lamivudine (3TC) as a switch simplified strategy in treatment-experienced human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients.Methods:Treatment-experienced HIV/AIDS patients who switched to a dual therapy containing DTG (50 mg, once daily) plus 3TC (300 mg, once daily) were included in Beijing You′an Hospital, Capital Medical University from September 2016 to May 2019. HIV RNA, CD4 + T lymphocyte count, blood lipid indexes, renal function indexes were collected when patients changed the treatment regimen (baseline) and after 48 weeks of treatment. Efficacy (HIV RNA<50 copies/mL) and safety of the dual therapy were analyzed. Statistical comparisons were performed using the Wilcoxon matched-pairs signed rank test. Results:The reasons for 33 patients switching the treatment regimen were virologic failure (four cases, 12.1%), simplification of regimen (11 cases, 33.3%), and drug toxicity (18 cases, 54.5%). The patients were treated with anti-retroviral therapy (ART) for 2.13 (1.05, 4.23) years before regimens switching. Twenty-nine (87.9%) patients were virologically suppressed at baseline, and four (12.1%) patients were virological failure. After switching to DTG plus 3TC, all 33 patients showed HIV RNA<50 copies/mL after 48 weeks of treatment. The baseline CD4 + T lymphocyte count was 543 (363, 595)/μL. After switching the treatment regimens for 48 weeks, CD4 + T lymphocyte count was significantly increased to 625 (455, 651)/μL, and the difference was statistically significant ( Z=3.14, P=0.002). Compared with baseline, low-density lipoprotein-cholesterol was increased after 48 weeks of treatment (2.35(1.80, 3.08) mmol/L vs 3.12(2.74, 3.87) mmol/L), while triglyceride (2.21(1.27, 4.37) mmol/L vs 1.61(1.20, 2.22) mmol/L), the ratio of total cholesterol to high-density lipoprotein-cholesterol (5.02 (4.13, 6.40) vs 4.70 (3.55, 5.35)) and estimated glomerular filtration rate (106.4(78.2, 118.2) mL/(min·1.73 m 2) vs 88.6 (75.7, 107.9) mL/(min·1.73 m 2)) were decreased. The differences were all statistically significant ( Z=4.89, 2.37, 2.09 and 2.83, respectively, all P<0.050). No patient discontinued due to adverse events. Conclusions:The use of dual therapy containing DTG and 3TC is effective and well-tolerated in treatment-experienced HIV/AIDS patients under any prior ART without significant adverse events.
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OBJECTIVE@#To screen differentially expressed gene (DEG) related to myelodysplastic syndrome (MDS) based on Gene Expression Omnibus (GEO) database, and explore the core genes and pathogenesis of MDS by analyzing the biological functions and related signaling pathways of DEG.@*METHODS@#The expression profiles of GSE4619, GSE19429, GSE58831 including MDS patients and normal controls were downloaded from GEO database. The gene expression analysis tool (GEO2R) of GEO database was used to screen DEG according to | log FC (fold change) |≥1 and P<0.01. David online database was used to annotate gene ontology function (GO). Metascape online database was used to enrich and analyze differential genes in Kyoto Encyclopedia of Genes and Genomes (KEGG). The protein-protein interaction network (PPI) was constructed by using STRING database. CytoHubba and Mcode plug-ins of Cytoscape were used to analyze the key gene clusters and hub genes. R language was used to diagnose hub genes and draw the ROC curve. GSEA enrichment analysis was performed on GSE19429 according to the expression of LEF1.@*RESULTS@#A total of 74 co-DEG were identified, including 14 up-regulated genes and 60 down regulated genes. GO enrichment analysis indicated that BP of down regulated genes was mainly enriched in the transcription and regulation of RNA polymerase II promoter, negative regulation of cell proliferation, and immune response. CC of down regulated genes was mainly enriched in the nucleus, transcription factor complexes, and adhesion spots. MF was mainly enriched in protein binding, DNA binding, and β-catenin binding. KEGG pathway was enriched in primary immunodeficiency, Hippo signaling pathway, cAMP signaling pathway, transcriptional mis-regulation in cancer and hematopoietic cell lineage. BP of up-regulated genes was mainly enriched in type I interferon signaling pathway and viral response. CC was mainly enriched in cytoplasm. MF was mainly enriched in RNA binding. Ten hub genes and three important gene clusters were screened by STRING database and Cytoscape software. The functions of the three key gene clusters were closely related to immune regulation. ROC analysis showed that the hub genes had a good diagnostic significance for MDS. GSEA analysis indicated that LEF1 may affect the normal function of hematopoietic stem cells by regulating inflammatory reaction, which further revealed the pathogenesis of MDS.@*CONCLUSION@#Bioinformatics can effectively screen the core genes and key signaling pathways of MDS, which provides a new strategy for the diagnosis and treatment of MDS.
Subject(s)
Humans , Computational Biology , Gene Expression Profiling , Gene Expression Regulation, Neoplastic , Gene Ontology , Myelodysplastic Syndromes/geneticsABSTRACT
Epidemiologic studies have indicated that dyslipidemia may facilitate the progression of cognitive dysfunction. We previously showed that patients with metabolic syndrome (MetS) had significantly higher plasma levels of electronegative very-low-density lipoprotein (VLDL) than did healthy controls. However, the effects of electronegative-VLDL on the brain and cognitive function remain unclear. In this study, VLDL isolated from healthy volunteers (nVLDL) or patients with MetS (metVLDL) was administered to mice by means of tail vein injection. Cognitive function was assessed by using the Y maze test, and plasma and brain tissues were analyzed. We found that mice injected with metVLDL but not nVLDL exhibited significant hippocampus CA3 neuronal cell loss and cognitive dysfunction. In mice injected with nVLDL, we observed mild glial cell activation in the medial prefrontal cortex (mPFC) and hippocampus CA3. However, in mice injected with metVLDL, plasma and brain TNF-α and Aß-42 levels and glial cell activation in the mPFC and whole hippocampus were higher than those in control mice. In conclusion, long-term exposure to metVLDL induced levels of TNF-α, Aß-42, and glial cells in the brain, contributing to the progression of cognitive dysfunction. Our findings suggest that electronegative-VLDL levels may represent a new therapeutic target for cognitive dysfunction.
Subject(s)
CA3 Region, Hippocampal , Cognitive Dysfunction , Lipoproteins, VLDL/toxicity , Prefrontal Cortex , Animals , CA3 Region, Hippocampal/metabolism , CA3 Region, Hippocampal/pathology , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/pathology , Dyslipidemias/metabolism , Humans , Inflammation/chemically induced , Inflammation/metabolism , Inflammation/pathology , Lipoproteins, VLDL/metabolism , Male , Metabolic Syndrome/metabolism , Mice , Prefrontal Cortex/metabolism , Prefrontal Cortex/pathologyABSTRACT
Aim To explore the cytotoxic and synergistic effects of decitabine and ruxolitinib on HEL cells with TET2 knockdown. Methods Stable TET2 knockdown by shRNA was established in HEL cell line. The change of cell proliferation was measured by CCK-8 assay. The median lethal dose (IC50) and colony formation assay were used to evaluate the cytotoxic effects of decitabine and ruxolitinib, the synergistic effects of which was further analyzed by Chou-Talalay method. Results The inhibition of TET2 increased the proliferative capacity of HEL cells. HEL cell lines became resistant to decitabine following shRNA-media- ted TET2 inactivation. Colony formation assay showed that the drug sensitivity of decitabine and ruxolitinib both decreased in TET2 knockdown HEL cells. The synergistic inhibitory effects of ruxolitinib and decitabine on TET2 knockdown HEL cells were observed. Conclusion The combination of ruxolitinib and decitabine may be an effective therapeutic strategy for accelerated or blast phase MPN patients with JAK2V6m and TET2 mutations.
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Human induced pluripotent stem cells (iPSCs) by four factors have the risks of teratoma formation and potential tumorigenicity. To overcome this major hurdle, we examined the mechanism(s) by which the cell cycle genes of embryonic cells were regulated. Naturally occurring embryonic stem cells (ESCs) possess two unique stemness properties: pluripotent differentiation into all cell types and self-renewal with no risk of tumor formation. Despite overwhelming reports describing iPSC pluripotency, there have been no observations of tumor prevention mechanism that suppresses tumor formation similar to that in naturally occurring ESCs. The ESC-specific microRNA (miRNA), miR-302, regulates human iPSC tumorigenicity through co-suppression of both cyclin E-CDK2 and cyclin D-CDK4/6 cell cycle pathways during G1-S phase transition. MiR-302 also silenced BMI-1, a cancer stem cell marker gene, to promote the expression of two senescence-associated tumor suppressor genes, p16Ink4a and p14/p19Arf. Together, the combinatory effect of reducing G1-S cell cycle transition and increasing p16/p14(p19) expression resulted in a relatively attenuated cell cycle rate similar to that of 2-to-8-cell-stage embryonic cells in early mammalian zygotes (20-24 h/cycle), as compared to the fast proliferation rate of iPSCs induced by four defined factors Oct4-Sox2-Klf4-c-Myc (12-16 h/cycle). In addition to the prevention of stem cell tumorigenicity, the mechanism underlying miR-302-mediated iPSCs also includes the initiation of global genomic DNA methylation, activation of ESC-specific gene expression, and inhibition of developmental signaling. Overall, we have established an effective protocol to express the intronic miR-302 cluster, according to its own natural biogenesis mechanism to generate tumor-free iPSCs for use in biology and therapy.
Subject(s)
Carcinogenesis/genetics , Cellular Reprogramming Techniques/methods , Induced Pluripotent Stem Cells/metabolism , MicroRNAs/genetics , Transfection/methods , Cellular Reprogramming , Electroporation/methods , Genetic Vectors/genetics , Humans , Introns , Kruppel-Like Factor 4ABSTRACT
Purpose@#Anterior gradient 3 (AGR3) belongs to human anterior gradient (AGR) family. The function of AGR3 on cancer remains unknown. This research aimed to investigate if AGR3 had prognostic values in invasive ductal carcinoma (IDC) of breast cancer and could promote tumor progression. @*Materials and Methods@#AGR3 expression was detected in breast benign lesions, ductal carcinoma in situ and IDC by immunohistochemistry analysis. AGR3’s correlations with clinicopathological features and prognosis of IDC patients were analyzed. By cell function experiments, collagen gel droplet-embedded culture drug sensitivity test and cytotoxic analysis, AGR3’s impacts on proliferation, invasion ability, and chemotherapeutic drug sensitivity of breast cancer cells were also detected. @*Results@#AGR3 was up-regulated in luminal subtype of histological grade I-II of IDC patients and positively correlated with high risks of recurrence and distant metastasis. AGR3 high expression could lead to bone or liver metastasis and predict poor prognosis of luminal B. In cell lines, AGR3 could promote proliferation and invasion ability of breast cancer cells which were consistent with clinical analysis. Besides, AGR3 could indicate poor prognosis of breast cancer patients treated with taxane but a favorable prognosis with 5-fluoropyrimidines. And breast cancer cells with AGR3 high expression were resistant to taxane but sensitive to 5-fluoropyrimidines. @*Conclusion@#AGR3 might be a potential prognostic indicator in luminal B subtype of IDC patients of histological grade I-II. And patients with AGR3 high expression should be treated with chemotherapy regimens consisting of 5-fluoropyrimidines but no taxane.
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Two new indium sulfate tellurites, namely, In2(SO4)(TeO3)(OH)2(H2O) and In3(SO4)(TeO3)2F3(H2O), were synthesized by hydrothermal method in a one-pot reaction. Their pure phase yields have been successfully optimized to 76% and 21%, respectively. In2(SO4)(TeO3)(OH)2(H2O) crystallized in centrosymmetric (CS) space group P21/n, while In3(SO4)(TeO3)2F3(H2O) formed a non-centrosymmetric (NCS) and chiral space group P212121. The CS compound features a 2D layered structure composed of 2D indium oxide layers decorated by sulfate tetrahedra and tellurite groups. The NCS compound displays a 3D network consisting of indium tellurite layers bridged by sulfate tetrahedra. Powder second harmonic generation measurements disclosed that In3(SO4)(TeO3)2F3(H2O) exhibits a weak frequency-doubling efficiency about 11% of the commercial KDP. Its powder laser damage threshold quantity was estimated to be 79.6 MW/cm2, which is about 36 times that of AGS. The two samples present wide optical band gaps of 4.86 and 4.10 eV, respectively, which were determined by Te, In, and O atoms based on density functional theory calculations.
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MiRNAs are naturally occurring, small, non-coding RNA molecules that post-transcriptionally regulate the expression of a large number of genes involved in various biological processes, either through mRNA degradation or through translation inhibition. MiRNAs play important roles in many aspects of physiology and pathology throughout the body, particularly in cancer, which have made miRNAs attractive tools and targets for translational research. The types of non-coding RNAs, biogenesis of miRNAs, circulating miRNAs, and direct delivery of miRNA were briefly reviewed. As a case of point, the role and perspective of miR-302, a family of ES-specific miRNA, on cancer, iPSCs, heart disease were presented.
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The hypothalamic paraventricular nucleus (PVN) is a crucial region involved in maintaining homeostasis through the regulation of cardiovascular, neuroendocrine, and other functions. The PVN provides a dominant source of excitatory drive to the sympathetic outflow through innervation of the brainstem and spinal cord in hypertension. We discuss current findings on the role of the PVN in the regulation of sympathetic output in both normotensive and hypertensive conditions. The PVN seems to play a major role in generating the elevated sympathetic vasomotor activity that is characteristic of multiple forms of hypertension, including primary hypertension in humans. Recent studies in the spontaneously hypertensive rat model have revealed an imbalance of inhibitory and excitatory synaptic inputs to PVN pre-sympathetic neurons as indicated by impaired inhibitory and enhanced excitatory synaptic inputs in hypertension. This imbalance of inhibitory and excitatory synaptic inputs in the PVN forms the basis for elevated sympathetic outflow in hypertension. In this review, we discuss the disruption of balance between glutamatergic and GABAergic inputs and the associated cellular and molecular alterations as mechanisms underlying the hyperactivity of PVN pre-sympathetic neurons in hypertension.
Subject(s)
Animals , Humans , Blood Pressure , Physiology , Excitatory Postsynaptic Potentials , Physiology , Hypertension , Hypothalamus , Physiology , Neurons , Physiology , Paraventricular Hypothalamic Nucleus , PhysiologyABSTRACT
Professor - believes that allergic rhinitis is mainly caused by deficiency of lung-spleen-kidney, combined with the attack of external pathogens, especially wind pathogens, which invade nasal orifices. Thus, three principles are established: syndrome differentiation and treatment, internal and external coherence, strengthening the root to eliminate pathogenic factors. For clinical practice, professor proposes the original acupuncture which takes the conception vessel and governor vessel as the general principles, takes syndrome differentiation as core, and takes regulating and as the major method. This acupuncture method integrates spirit and , bases on verified method and acupoint, combines acupuncture and medication, and achieves satisfactory results.
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Humans , Acupuncture , Acupuncture Points , Acupuncture Therapy , Meridians , Rhinitis, Allergic , TherapeuticsABSTRACT
Objective To investigate the relationship between hemoglobin and blood pressure of pregnant women in Zhoushan islands, so as to provide scientific evidence for the etiological study of gestational hypertension. Methods A retrospective study was conducted among 1 383 pregnant women who received perinatal care in Zhoushan Maternal and Child Health Hospital of Zhejiang Province from January 2017 to June 2018. Pregnant women were monitored for hemoglobin content and blood pressure in the early, middle and late pregnancy. The multivariate linear regression was used to analyze the relationship between hemoglobin content and blood pressure in different pregnancy. Results The incidence of anemia in early, middle and late pregnancy was 7.74%, 25.45% and 15.76% respectively. The multivariate linear regression showed that hemoglobin levels during pregnancy had effects on systolic blood pressure in early, middle and late pregnancy, and the earlier hemoglobin levels were monitored, the more obvious the effect on systolic blood pressure was.With the increase of hemoglobin level, systolic blood pressure increased, such as the effect of hemoglobin on systolic blood pressure in early pregnancy, mid-pregnancy and late pregnancy. Hemoglobin of first trimster had the greatest effect (β=0.10, P<0.001), Hemoglobin of second trimester had no obvious effect, and that of third trimester had the second effect (β=0.04, P=0.027).Hemoglobin levels and diastolic blood pressure levels were similar to their relationship with systolic blood pressure. Conclusions Hemoglobin levels during pregnancy have significant effects on systolic and diastolic blood pressure in first, second and third trimsters of pregnancy. Regular measurement of hemoglobin levels during pregnancy can improve the health of pregnant women.
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OBJECTIVE@#To explore the expression, localization and regulatory effect on mitochondrial calcium signaling of Rictor in embryonic stem cell-derived cardiomyocytes (ESC-CMs).@*METHODS@#Classical embryonic stem cell cardiomyogenesis model was used for differentiation of mouse embryonic stem cells into cardiomyocytes. The location of Rictor in ESC-CMs was investigated by immunofluorescence and Western blot. The expression of Rictor in mouse embryonic stem cells was interfered with lentiviral technology, then the superposition of mitochondria and endoplasmic reticulum (ER) in ESC-CMs was detected with immunofluorescence method; the cellular ultrastructure of ESC-CMs was observed by transmission electron microscope; the mitochondrial calcium transients of ESC-CMs was detected by living cell workstation;immunoprecipitation was used to detect the interaction between 1,5,5-trisphosphate receptor (IP3 receptor, IP3R), glucose-regulated protein 75 (Grp75) and voltage-dependent anion channel 1 (VDAC1) in mitochondrial outer membrane; the expression of mitochondrial fusion protein (mitonusin-2, Mfn2) was detected by Western blot.@*RESULTS@#Rictor was mainly localized in the endoplasmic reticulum and mitochondrial-endoplasmic reticulum membrane (MAM) in ESC-CMs. Immunofluorescence results showed that Rictor was highly overlapped with ER and mitochondria in ESC-CMs. After mitochondrial and ER were labeled with Mito-Tracker Red and ER-Tracker Green, it was demonstrated that the mitochondria of the myocardial cells in the Rictor group were scattered, and the superimposition rate of mitochondria and ER was lower than that of the negative control group (<0.01). The MAM structures were decreased in ESC-CMs after knockdown of Rictor. The results of the living cell workstation showed that the amplitude of mitochondrial calcium transients by ATP stimulation in ESC-CMs was decreased after knockdown of Rictor (<0.01). The results of co-immunoprecipitation showed that the interaction between IP3R, Grp75 and VDAC1 in the MAM structure of the cardiomyocytes in the Rictor group was significantly attenuated (<0.01); the results of Western blot showed that the expression of Mfn2 protein was significantly decreased (<0.01).@*CONCLUSIONS@#Using lentiviral technology to interfere Rictor expression in mouse embryonic stem cells, the release of calcium from the endoplasmic reticulum to mitochondria in ESC-CMs decreases, which may be affected by reducing the interaction of IP3R, Grp75, VDAC1 and decreasing the expression of Mfn2, leading to the damage of MAM structure.
Subject(s)
Animals , Mice , Calcium Signaling , Genetics , Gene Expression Regulation , Genetics , Gene Knockdown Techniques , Mitochondria , Physiology , Mouse Embryonic Stem Cells , Myocytes, Cardiac , Physiology , Protein Transport , Rapamycin-Insensitive Companion of mTOR Protein , Genetics , MetabolismABSTRACT
Through summarizing and analyzing a large number of documents and reports of large academic conferences in China, the current situation and the prospect of individualized drug delivery model were analyzed based on folate metabolic gene in pharmaceutical care. Folate metabolic genemethylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase reductase (MTRR) A66G were related with development of multiple diseases. Its polymorphism guidesindividualized drug administrationto increase the efficacy of drugs or decrease adverse effects.