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1.
Mol Pain ; 19: 17448069231159356, 2023.
Article in English | MEDLINE | ID: mdl-36750423

ABSTRACT

Aim: The aim of this study is to investigate the mechanism and interaction of microRNA-181a (miR-181a), toll-like receptor 4 (TLR4) and nuclear factor-kappa B (NF-κB) in gastric hypersensitivity in diabetic rats. Methods: Diabetes was induced by a single intraperitoneal injection of streptozotocin (STZ; 65 mg/kg) in female SD rats. Gastric balloon distension technique was used to measure diabetic gastric hypersensitivity. Gastric-specific (T7-T10) dorsal root ganglion (DRG) neurons were acutely dissociated to measure excitability with patch-clamp techniques. Western blotting was employed to measure the expressions of TLR4, TRAF6 and NF-κB subunit p65 in T7-T10 DRGs. The expressions of microRNAs in T7-T10 DRGs were measured with quantitative real-time PCR and fluorescence in situ hybridization. Dual-luciferase reporter gene assay was used to detect the targeting regulation of microRNAs on TLR4. Results: (1) Diabetic rats were more sensitive to graded gastric balloon distention at 2 and 4 weeks. (2) The expression of TLR4 was significantly up-regulated in T7-T10 DRGs of diabetic rats. Intrathecal injection of CLI-095 (TLR4-selective inhibitor) attenuated diabetic gastric hypersensitivity, and markedly reversed the hyper-excitability of gastric-specific DRG neurons. (3) The expressions of miR-181a and miR-7a were significantly decreased in diabetic rats. MiR-181a could directly regulate the expression of TLR4, while miR-7a couldn't. (4) Intrathecal injection of miR-181a agomir down-regulated the expression of TLR4, reduced the hyper-excitability of gastric-specific neurons, and alleviated gastric hypersensitivity. (5) p65 and TLR4 were co-expressed in Dil-labeled DRG neurons. (6) Inhibition of p65 attenuated diabetic gastric hypersensitivity and hyper-excitability of gastric-specific DRG neurons. (7) The expression of TRAF6 was significantly up-regulated in diabetic rats. CLI-095 treatment also reduced the expression of TRAF6 and p65. Conclusion: The reduction of microRNA-181a in T7-T10 DRGs might up-regulate TLR4 expression. TLR4 activated NF-κB through MyD88-dependent signaling pathway, increased excitability of gastric-specific DRG neurons, and contributed to diabetic gastric hypersensitivity.


Subject(s)
Diabetes Mellitus, Experimental , MicroRNAs , Rats , Female , Animals , NF-kappa B/metabolism , Toll-Like Receptor 4/metabolism , Rats, Sprague-Dawley , In Situ Hybridization, Fluorescence , TNF Receptor-Associated Factor 6/metabolism , MicroRNAs/genetics
2.
BMC Anesthesiol ; 21(1): 296, 2021 11 27.
Article in English | MEDLINE | ID: mdl-34836503

ABSTRACT

BACKGROUND: The purpose of this study was to retrospectively analyze clinical characteristics and prognostic risk factors of urosepsis patients admitted to two intensive care units in Shanghai, China. METHODS: Clinical data from patients diagnosed with urosepsis were retrospectively retrieved and analyzed from ICU in two regional medical centers from January 2015 to December 2019. RESULTS: Two hundred two patients were included in the subsequent analysis eventually, with an average age of 72.02 ± 9.66 years, 79.21% of the patients were female and the mortality rate of 15.84%.The proportion of patients with chronic underlying diseases such as diabetes and hypertension was relatively high (56.44, 49.50%, respectively), and the incidence of shock was also high (41.58%) correspondingly. The most common pathogen isolated was Escherichia coli (79.20%), of which the extended-spectrumß-lactamases (ESBLs)(+) accounted for 42.57%. In multivariate analysis, the strongest predictors for death were mechanical ventilation (OR 7.260, 95% CI 2.200-23.963; P = 0.001),chronic kidney disease (CKD) (OR 5.140, 95% CI 1.596-16.550; P = 0.006), APACHE II score (OR 1.321, 95% CI 1.184-1.473; P < 0.001) and lactate (OR 1.258, 95% CI 1.037-1.527; P = 0.020). Both APACHE II score and lactate had the ideal predictive value, with the area under the ROC curve (AUC) of 0.858 and 0.805 respectively. CONCLUSION: The patients with urosepsis were characterized by a higher proportion of female, older age, more percentage of comorbidities in this region, and patients with ESBLs (+) Escherichia coli infection were more prone to shock. Mechanical ventilation, comorbidity with CKD, APACHE II score and lactate were independent risk factors for death in urosepsis patient, but lactate level and APACHE II score had better predictive value for prognosis.


Subject(s)
Sepsis/blood , Sepsis/epidemiology , Urinary Tract Infections/blood , Urinary Tract Infections/epidemiology , Age Distribution , Aged , China/epidemiology , Critical Illness , Female , Humans , Intensive Care Units , Lactic Acid/blood , Male , Patient Acuity , Prognosis , Renal Insufficiency, Chronic/blood , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/epidemiology , Respiration, Artificial/statistics & numerical data , Retrospective Studies , Risk Factors , Sepsis/diagnosis , Sex Distribution , Survival Analysis , Urinary Tract Infections/diagnosis
3.
Int J Clin Pract ; 75(12): e14865, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34523203

ABSTRACT

BACKGROUND: Evidence shows that simplified SOFA scoring system has better clinical practice. OBJECTIVE: This study aimed to validate and compare the scores acquired with simplified organ dysfunction criteria optimized for electronic health records (eSOFA), and simplified and accurate sequential organ failure assessment (sa-SOFA) for their accuracies in predicting the prognosis of septic patients. METHODS: This retrospective observational study was conducted at three major academic hospitals. Clinical data from 574 patients diagnosed with sepsis following the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)were retrospectively retrieved and analysed. Scores from the quick sequential organ failure assessment (qSOFA) and sequential organ failure assessment (SOFA) were used as reference scores. The area under the receiver operating characteristic curve (AUROC) was used to assess the performance of eSOFA and sa-SOFA scores in predicting in-hospital mortality. RESULTS: AUROC analysis demonstrated the predictability of the four scoring systems for sepsis surveillance, listed in descending order as: sa-SOFA, 0.790 (95% confidence interval [CI]: 0.754-0.822); SOFA, 0.774 (95% CI: 0.738-0.808); eSOFA, 0.729 (95% CI: 0.691-0.765); and qSOFA, 0.618 (95% CI: 0.577-0.658). Moreover, sa-SOFA and SOFA scores (Z = 1.950, P = .051) did not significantly differ from each other in discriminatory power, but the sa-SOFA score had a higher power than eSOFA score (P values < .001). CONCLUSION: sa-SOFA appeared to have performed better than eSOFA score for predicting in-hospital mortality in patients' sepsis. Further large prospective studies are needed to externally validate.


Subject(s)
Organ Dysfunction Scores , Sepsis , Hospital Mortality , Humans , Intensive Care Units , Prognosis , ROC Curve , Retrospective Studies , Sepsis/diagnosis
4.
World J Stem Cells ; 13(1): 115-127, 2021 Jan 26.
Article in English | MEDLINE | ID: mdl-33584983

ABSTRACT

BACKGROUND: Collagen is one of the most commonly used natural biomaterials for tendon tissue engineering. One of the possible practical ways to further enhance tendon repair is to combine a porous collagen sponge scaffold with a suitable growth factor or cytokine that has an inherent ability to promote the recruitment, proliferation, and tenogenic differentiation of cells. However, there is an incomplete understanding of which growth factors are sufficient and optimal for the tenogenic differentiation of rat bone marrow mesenchymal stem cells (BMSCs) in a collagen sponge-based 3D culture system. AIM: To identify one or more ideal growth factors that benefit the proliferation and tenogenic differentiation of rat BMSCs in a porous collagen sponge scaffold. METHODS: We constructed a 3D culture system based on a type I collagen sponge scaffold. The surface topography of the collagen sponge scaffold was observed by scanning electron microscopy. Primary BMSCs were isolated from Sprague-Dawley rats. Cell survival on the surfaces of the scaffolds with different growth factors was assessed by live/dead assay and CCK-8 assay. The mRNA and protein expression levels were confirmed by quantitative real-time polymerase chain reaction and Western blot, respectively. The deposited collagen was assessed by Sirius Red staining. RESULTS: Transforming growth factor ß1 (TGF-ß1) showed great promise in the tenogenic differentiation of BMSCs compared to growth differentiation factor 7 (GDF-7) and insulin-like growth factor 1 (IGF-1) in both the 2D and 3D cultures, and the 3D culture enhanced the differentiation of BMSCs into tenocytes well beyond the level of induction in the 2D culture after TGF-ß1 treatment. In the 2D culture, the proliferation of the BMSCs showed no significant changes compared to the control group after TGF-ß1, IGF-1, or GDF-7 treatment. However, TGF-ß1 and GDF-7 could increase the cell proliferation in the 3D culture. Strangely, we also found more dead cells in the BMSC-collagen sponge constructs that were treated with TGF-ß1. Moreover, TGF-ß1 promoted more collagen deposition in both the 2D and 3D cultures. CONCLUSION: Collagen sponge-based 3D culture with TGF-ß1 enhances the responsiveness of the proliferation and tenogenic differentiation of rat BMSCs.

5.
Epigenomics ; 12(10): 843-857, 2020 05.
Article in English | MEDLINE | ID: mdl-32212929

ABSTRACT

Aim: To study the expression pattern of circular RNAs in diabetic peripheral neuropathy. Materials & methods: Transmission electron microscopy was used to observe the ultrastructure of sciatic nerves and dorsal root ganglion (DRGs). circRNAs in DRGs were identified with high-throughput RNA sequencing. Whole-genome mRNAs were detected by a chip scan. Results: The ultrastructure of sciatic nerves and DRGs in diabetes mellitus mice changed significantly. A total of 11,004 circRNAs and 15 differentially expressed circRNAs, as well as 35,368 mRNAs and 133 differentially expressed mRNAs were identified in DRGs between wild-type and diabetes mellitus mice. 11 circRNAs and 14 mRNAs have a significant correlation using strict coexpression analysis. The expression of circRNA.4614 was validated to be upregulated significantly. Conclusion: Our study suggested that circRNAs might be involved in the regulation of mRNA expressions in diabetic peripheral neuropathy.


Subject(s)
Diabetic Neuropathies/genetics , RNA, Circular/genetics , RNA, Messenger/genetics , Animals , Ganglia, Spinal/ultrastructure , Gene Expression Profiling , High-Throughput Nucleotide Sequencing , Mice , Mice, Inbred C57BL , Microscopy, Electron, Transmission , Sciatic Nerve/ultrastructure
6.
CNS Neurosci Ther ; 26(7): 762-772, 2020 07.
Article in English | MEDLINE | ID: mdl-32175676

ABSTRACT

AIMS: Painful diabetic neuropathy (PDN) is a refractory complication of diabetes. The study aimed to investigate the role of α-lipoic acid (ALA) on the regulation of transient receptor potential vanilloid-1 (TRPV1) in dorsal root ganglion (DRG) neurons of rats with diabetes. METHODS: Whole-cell patch-clamp recordings were employed to measure neuronal excitability in DiI-labeled DRG neurons of control and streptozotocin (STZ)-induced diabetic rats. Western blotting and immunofluorescence assays were used to determine the expression and location of NF-κBp65 and TRPV1. RESULTS: STZ-induced hindpaw pain hypersensitivity and neuronal excitability in L4-6 DRG neurons were attenuated by intraperitoneal injection with ALA once a day lasted for one week. TRPV1 expression was enhanced in L4-6 DRGs of diabetic rats compared with age-matched control rats, which was also suppressed by ALA treatment. In addition, TRPV1 and p65 colocated in the same DRG neurons. The expression of p65 was upregulated in L4-6 DRGs of diabetic rats. Inhibition of p65 signaling using recombinant lentiviral vectors designated as LV-NF-κBp65 siRNA remarkably suppressed TRPV1 expression. Finally, p65 expression was downregulated by ALA treatment. CONCLUSION: Our findings demonstrated that ALA may alleviate neuropathic pain in diabetes by regulating TRPV1 expression via affecting NF-κB.


Subject(s)
Antioxidants/therapeutic use , Diabetes Mellitus, Experimental/metabolism , NF-kappa B/metabolism , Neuralgia/metabolism , TRPV Cation Channels/metabolism , Thioctic Acid/therapeutic use , Animals , Antioxidants/pharmacology , Diabetes Mellitus, Experimental/drug therapy , Female , Ganglia, Spinal/drug effects , Ganglia, Spinal/metabolism , NF-kappa B/antagonists & inhibitors , Neuralgia/drug therapy , Rats , Rats, Sprague-Dawley , TRPV Cation Channels/antagonists & inhibitors , Thioctic Acid/pharmacology
7.
Mol Pain ; 15: 1744806919838659, 2019.
Article in English | MEDLINE | ID: mdl-30838902

ABSTRACT

BACKGROUND AND AIM: Diabetic neuropathic pain is a refractory and disabling complication of diabetes mellitus. The pathogenesis of the diabetic neuropathic pain is still unclear, and treatment is insufficient. The aim of this study is to investigate the roles of glucose-6-phosphate dehydrogenase (G6PD) and toll-like receptor 4 (TLR4) in neuropathic pain in rats with diabetes. METHODS: Type 1 diabetes model was induced by intraperitoneal injection of streptozotocin (STZ, 75 mg/kg) in adult female Sprague-Dawley rats. Paw withdrawal threshold and paw withdrawal latency of rats were measured by von Frey filaments and thermal radiation, respectively. The expressions of G6PD and TLR4 in L4-L6 dorsal root ganglions (DRGs) were measured by western blotting and quantitative real-time polymerase chain reaction analysis. Fluorescent immunohistochemistry was employed to detect expressions of G6PD and TLR4 and co-location of G6PD with TLR4. RESULTS: The mRNA and protein expression levels of G6PD in DRGs were significantly decreased in diabetic rats when compared with age-matched control rats. Upregulation of G6PD by intrathecal injection of G6PD overexpression adenovirus markedly attenuated hindpaw pain hypersensitivity of diabetic rats. The mRNA and protein expression levels of TLR4 in DRGs of diabetic rats were significantly increased when compared with control rats. Intrathecal injection of TLR4-selective inhibitor CLI-095 attenuated diabetic pain in dose- and time-dependent manners. Furthermore, G6PD and TLR4 were co-localized in DRG neurons. Intrathecal injection of G6PD overexpression adenovirus greatly reduced TLR4 expression, while intrathecal injection of CLI-095 had no significant effect on G6PD expression in diabetic rats. CONCLUSIONS: Our results suggest that decrease in G6PD expression was involved in diabetic peripheral neuropathic pain, which was most likely through upregulation of TLR4 expression in the DRGs of rats.


Subject(s)
Diabetic Neuropathies/drug therapy , Diabetic Neuropathies/metabolism , Glucosephosphate Dehydrogenase/metabolism , Toll-Like Receptor 4/metabolism , Animals , Female , Ganglia, Spinal/drug effects , Ganglia, Spinal/metabolism , Glucosephosphate Dehydrogenase/genetics , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects , Sulfonamides/therapeutic use , Toll-Like Receptor 4/antagonists & inhibitors , Toll-Like Receptor 4/genetics
8.
Bioorg Med Chem Lett ; 28(6): 1149-1153, 2018 04 01.
Article in English | MEDLINE | ID: mdl-29496368

ABSTRACT

A series of cinnamic acid derivatives and its heteroaromatic ring analogues were synthesized and evaluated for acaricidal activity in vitro against Psoroptes cuniculi, a mange mite. Among them, eight compounds showed the higher activity with median lethal concentrations (LC50) of 0.36-1.07mM (60.4-192.1µg/mL) and great potential for the development of novel acaricidal agent. Compound 40 showed both the lowest LC50 value of 0.36mM (60.4µg/mL) and the smallest median lethal time (LT50) of 2.6h at 4.5mM, comparable with ivermectin [LC50=0.28mM (247.4µg/mL), LT50=8.9h], an acaricidal drug standard. SAR analysis showed that the carbonyl group is crucial for the activity. The type and chain length of the alkoxy in the ester moiety and the steric hindrance near the ester group significantly influence the activity. The esters were more active than the corresponding thiol esters, amides, ketones or acids. Replacement of the phenyl group of cinnamic esters with α-pyridyl or α-furanyl significantly increase the activity. Thus, a series of cinnamic esters and its heteroaromatic ring analogues with excellent acaricidal activity emerged.


Subject(s)
Acaricides/pharmacology , Cinnamates/pharmacology , Psoroptidae/drug effects , Acaricides/chemical synthesis , Acaricides/chemistry , Animals , Cinnamates/chemical synthesis , Cinnamates/chemistry , Dose-Response Relationship, Drug , Molecular Structure , Structure-Activity Relationship
9.
PLoS One ; 13(1): e0190299, 2018.
Article in English | MEDLINE | ID: mdl-29293569

ABSTRACT

DNA methylation is an important mechanism of epigenetic modification. Methylation changes during stress responses and developmental processes have been well studied; however, their role in plant adaptation to the day/night cycle is poorly understood. In this study, we detected global methylation patterns in leaves of the black poplar Populus nigra 'N46' at 8:00 and 24:00 by methylated DNA immunoprecipitation sequencing (MeDIP-seq). We found 10,027 and 10,242 genes to be methylated in the 8:00 and 24:00 samples, respectively. The methylated genes appeared to be involved in multiple biological processes, molecular functions, and cellular components, suggesting important roles for DNA methylation in poplar cells. Comparing the 8:00 and 24:00 samples, only 440 differentially methylated regions (DMRs) overlapped with genic regions, including 193 hyper- and 247 hypo-methylated DMRs, and may influence the expression of 137 downstream genes. Most hyper-methylated genes were associated with transferase activity, kinase activity, and phosphotransferase activity, whereas most hypo-methylated genes were associated with protein binding, ATP binding, and adenyl ribonucleotide binding, suggesting that different biological processes were activated during the day and night. Our results indicated that methylated genes were prevalent in the poplar genome, but that only a few of these participated in diurnal gene expression regulation.


Subject(s)
Circadian Rhythm , DNA Methylation , Genome, Plant , Populus/genetics , Adaptation, Physiological , Darkness , Immunoprecipitation , Light , Plant Leaves/metabolism , Populus/physiology
10.
J Huazhong Univ Sci Technolog Med Sci ; 37(5): 807-810, 2017 Oct.
Article in English | MEDLINE | ID: mdl-29058300

ABSTRACT

We report one case of pediatric acute myeloid leukemia type 2 (AML-M2) who presented with karyotypic aberration of trisomy 21 with the t(5;11) chromosomal translocation. The patient achieved complete remission after two cycles of chemotherapy of daunorubicin, cytarabine and etoposide. Then, follow-up cytogenetic analysis from bone marrow cell cultures demonstrated a normal karyotype of 46, XY. After 9 years, the patient relapsed and the karyotypic abnormalities of trisomy 21 with t(5;11) reappeared. It was concluded that trisomy 21 with t(5; 11) is a new unfavorable cytogenetic aberration in AML-M2.


Subject(s)
Chromosomes, Human, Pair 11/genetics , Chromosomes, Human, Pair 5/genetics , Down Syndrome/genetics , Leukemia, Myeloid, Acute/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Child, Preschool , Chromosome Aberrations , Follow-Up Studies , Humans , Leukemia, Myeloid, Acute/genetics , Male , Remission Induction , Translocation, Genetic
11.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-297203

ABSTRACT

The study reports a female neonate with a gestational age of 29weeks and a birth weight of 1 210 g. Ten minutes after birth, the neonate was admitted to the hospital due to shortness of breath. Several days after birth, the neonate presented with hyperglycemia, polyuria, and poor weight gain, accompanied by azotemia, hypochloremic metabolic alkalosis, hypokalemia, and hyponatremia. Laboratory examinations showed elevated levels of aldosterone, renin, and angiotensin II. Gene detection revealed SLC12A1 gene mutation. Neonatal Bartter syndrome was thus confirmed. The neonate was treated with sodium and potassium supplements, and was followed up for 8 months. During the follow-up, the mental and neural development of the neonate was almost normal at the corrected age, and regular reexaminations showed slight metabolic alkalosis and almost normal electrolyte levels. For the neonates who have the symptoms of unexplainable polyurine and electrolyte disorders, it is important to examine the levels of aldosterone, renin and angiotensin. A definite diagnosis of neonatal Bartter syndrome can be made based on the presence of SLC12A1 gene mutation.


Subject(s)
Female , Humans , Infant, Newborn , Acidosis , Bartter Syndrome , Therapeutics , Hypokalemia , Recurrence , Weight Gain
12.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-333422

ABSTRACT

We report one case of pediatric acute myeloid leukemia type 2 (AML-M2) who presented with karyotypic aberration of trisomy 21 with the t(5;ll) chromosomal translocation.The patient achieved complete remission after two cycles of chemotherapy of daunorubicin,cytarabine and etoposide.Then,follow-up cytogenetic analysis from bone marrow cell cultures demonstrated a normal karyotype of 46,XY.After 9 years,the patient relapsed and the karyotypic abnormalities of trisomy 21 with t(5;ll) reappeared.It was concluded that trisomy 21 with t(5;11) is a new unfavorable cytogenetic aberration in AML-M2.

13.
Article in Chinese | WPRIM (Western Pacific) | ID: wpr-261176

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the influence of delayed cord clamping (DCC) on preterm infants with a gestational age of <32 weeks.</p><p><b>METHODS</b>Ninety preterm infants with a gestational age of <32 weeks delivered naturally from January to December, 2015 were enrolled and randomly divided into DCC group (46 infants) and immediate cord clamping (ICC) group (44 infants). The routine blood test results, total amount of red blood cell transfusion, blood gas parameters, mean arterial pressure, bilirubin peak, total time of phototherapy, and incidence rates of necrotizing enterocolitis, late-onset sepsis, intracranial hemorrhage, retinopathy, and bronchopulmonary dysplasia were compared between the two groups.</p><p><b>RESULTS</b>Compared with the ICC group, the DCC group had significantly higher levels of hemoglobin, hematocrit, mean arterial pressure, and standard base excess (P<0.05), as well as a significantly lower percentage of preterm infants who underwent volume expansion and dopamine treatment and a significantly lower amount of red blood cell transfusion (P<0.05). The body temperature, pH value, HCO3(-) concentration, serum bilirubin peak, total time of phototherapy, and incidence rates of late-onset sepsis, retinopathy, grade≥2 intracranial hemorrhage, and grade≥2 neonatal necrotizing enterocolitis showed no significant differences between the two groups (P>0.05).</p><p><b>CONCLUSIONS</b>DCC is a safe clinical intervention and can improve the prognosis of preterm infants with a gestational age of <32 weeks.</p>


Subject(s)
Female , Humans , Infant, Newborn , Male , Constriction , Delivery, Obstetric , Methods , Gestational Age , Blood , Infant, Premature , Time Factors , Umbilical Cord
14.
Molecules ; 19(6): 8051-66, 2014 Jun 16.
Article in English | MEDLINE | ID: mdl-24936707

ABSTRACT

As part of our continuing research on isoquinoline acaricidal drugs, this paper reports the preparation of a series of the 2-aryl-1-cyano-1,2,3,4-tetrahydroisoquinolines with various substituents on the N-phenyl ring, their in vitro acaricidal activities against Psoroptes cuniculi, a mange mite, and discusses their SAR as well. The structures of all compounds, including 12 new ones, were elucidated by analysis of UV, IR, NMR, ESI-MS, HR-MS spectra and X-ray diffraction experiments. All target compounds showed varying degrees of activity at 0.4 mg/mL. Compound 1 showed the strongest activity, with a 50% lethal concentration value (LC50) of 0.2421 µg/mL and 50% lethal time value (LT50) of 7.79 h, comparable to the standard drug ivermectin (LC50 = 0.2474 µg/mL; LT50 = 20.9 h). The SAR showed that the substitution pattern on the N-aromatic ring exerted a significant effect on the activity. The substituents 2'-F, 3'-F, 2'-Cl, 2'-Br and 2'-CF3 remarkably enhanced the activity. Generally, for the isomers with the same substituents at different positions, the order of the activity was ortho > meta > para. It was concluded that the target compounds represent a class of novel promising candidates or lead compounds for the development of new tetrahydroisoquinoline acaricidal agents.


Subject(s)
Acaricides/chemical synthesis , Acaricides/pharmacology , Psoroptidae/drug effects , Tetrahydroisoquinolines/chemistry , Acaricides/chemistry , Animals , Magnetic Resonance Spectroscopy , Structure-Activity Relationship , X-Ray Diffraction
15.
Zhongguo Dang Dai Er Ke Za Zhi ; 16(2): 129-34, 2014 Feb.
Article in Chinese | MEDLINE | ID: mdl-24568904

ABSTRACT

OBJECTIVE: To study the expression of ecotropic viral integration site (EVI1) gene in childhood acute myeloid leukemia (AML) and the clinical features of EVI1-positive children with AML. METHODS: The clinical data of EVI1-positive children with AML were collected and analyzed. RT-PCR and real-time quantitative PCR were used for qualitative and quantitative analysis of expression of EVI1. Flow cytometry (FCM) was used for determining the immunophenotypes of bone marrow cells. Multiparameter FCM was used for monitoring minimal residual disease. The karyotypes were determined. RESULTS: Of 241 children with AML, 33 (13.7%) were positive for EVI1 expression. There were no significant differences in age at first visit as well as the white blood cell count, hemoglobin level, and platelet count in peripheral blood between EVI1-positive and EVI1-negative children with AML (P>0.05), but EVI1-positive children had a significantly increased proportion of females compared with EVI1-negative children (P<0.05). The change in EVI1 expression was not synchronous with clinical remission and the change of MRD: some children had clinical remission or negative conversion of MRD before negative conversion of EVI1, while some had negative conversion of EVI1 before clinical remission or while MRD showed positive. EVI1 gene was usually co-expressed with other fusion genes. CD33 (100%), CD38 (88%), and HLADR (76%) were highly expressed in EVI1-positive children with AML. Abnormal chromosome structure or number was found in 15 patients. Compared with EVI1-negative children, EVI1-positive children had significantly lower complete remission rates after the first course of treatment (P<0.05). CONCLUSIONS: EVI1-positive children with AML have a poor short-term prognosis. In the development of AML, the activation of EVI1 gene is not isolated, but the result of interactions with other genes or chromosome abnormalities, and the mechanism of activation and its function need further study.


Subject(s)
DNA-Binding Proteins/genetics , Leukemia, Myeloid, Acute/genetics , Proto-Oncogenes/genetics , Transcription Factors/genetics , Adolescent , Child , Child, Preschool , Chromosome Aberrations , Female , Flow Cytometry , Gene Expression Regulation, Neoplastic , Humans , Immunophenotyping , Infant , Leukemia, Myeloid, Acute/immunology , MDS1 and EVI1 Complex Locus Protein , Male , Neoplasm, Residual , Prognosis
16.
PLoS One ; 7(10): e47811, 2012.
Article in English | MEDLINE | ID: mdl-23094096

ABSTRACT

The microRNAs (miRNAs) miR482 and miR1448 are disease resistance-related miRNAs; the former is ubiquitously distributed in seed plants whereas the latter has only been reported in Populus trichocarpa. The precursor and mature sequences of poplar miR1448 are highly homologous to those of poplar miR482, and these two miRNAs are located in one transcript as a polycistron. Therefore, we hypothesized that the MIR1448 gene may have evolved from the MIR482 gene in poplar. However, the molecular evolution patterns of this process remain unclear. In this study, utilizing cloning and Blast analysis in NCBI ESTs and whole-genome shotgun contigs (WGS) dataset, we determined that the MIR482-MIR1448 polycistron is a family-specific clustered miRNA in Salicaceae. Moreover, phylogenetic analysis illustrated that MIR1448 is the product of a tandem duplication event from MIR482. Nucleotide substitution analysis revealed that both MIR482 and MIR1448 have more rapid evolution ratios than ribosomal DNA (rDNA) genes, and that compensatory mutations that occurred in the stem region of the secondary structure were the main mechanisms that drove the evolution of these MIRNA genes. Furthermore, by comparing the substitution patterns in the miRNA-target complexes of miR482 and miR1448, we inferred that co-evolution between miRNAs and their targets was the major force that drove the "duplicated MIR482" evolve to MIR1448. We propose a novel miRNA-target pairing pattern called the "frameshift targeted mechanism" to explain the gain of target genes by miR1448. The results also imply that the major role of miR482 was in resistance to disease or other stresses via NBS-LRR proteins, whereas the biological functions of miR1448 are more diverse.


Subject(s)
Evolution, Molecular , Gene Expression Regulation, Plant , Genes, Plant , MicroRNAs , Phylogeny , Populus/genetics , RNA, Plant , Arabidopsis/genetics , Base Sequence , Cloning, Molecular , Gene Duplication , Molecular Sequence Data , Multigene Family , Oryza/genetics , Populus/classification , Populus/immunology , RNA Folding , Sequence Homology, Nucleic Acid
17.
PLoS One ; 7(9): e44968, 2012.
Article in English | MEDLINE | ID: mdl-23028709

ABSTRACT

MicroRNAs (miRNAs), a type of short (21-23 nucleotides), non-coding RNA molecule, mediate repressive gene regulation through RNA silencing at the post-transcriptional level, and play an important role in defense and response to abiotic and biotic stresses. In the present study, Affymetrix® miRNA Array, real-time quantitative PCR (qPCR) for miRNAs and their targets, and miRNA promoter analysis were used to validate the gene expression patterns of miRNAs in Populus trichocarpa plantlets induced with the poplar stem canker pathogen, Botryosphaeria dothidea. Twelve miRNAs (miR156, miR159, miR160, miR164, miR166, miR168, miR172, miR319, miR398, miR408, miR1448, and miR1450) were upregulated in the stem bark of P. trichocarpa, but no downregulated miRNAs were found. Based on analysis of the miRNAs and their targets, a potential co-regulatory network was developed to describe post-transcriptional regulation in the pathological development of poplar stem canker. There was highly complex cross-talk between diverse miRNA pathway responses to biotic and abiotic stresses. The results suggest that miR156 is probably an integral component of the miRNA response to all environmental stresses in plants. Cis-regulatory elements were binding sites for the transcription factors (TFs) on DNA. Promoter analysis revealed that TC-rich repeats and a W1-box motif were both tightly related disease response motifs in Populus. Promoter analysis and target analysis of miRNAs also revealed that some TFs regulate their activation/repression. Furthermore, a feedback regulatory network in the pathological development of poplar stem canker is provided. The results confirm that miRNA pathways regulate gene expression during the pathological development of plant disease, and provide new insights into understanding the onset and development of poplar stem canker.


Subject(s)
Ascomycota/physiology , Gene Expression Regulation, Plant , MicroRNAs/metabolism , Plant Diseases/microbiology , Populus/genetics , Populus/microbiology , RNA, Plant/metabolism , Genes, Plant/genetics , MicroRNAs/genetics , Populus/physiology , Promoter Regions, Genetic/genetics , RNA, Plant/genetics , Stress, Physiological , Up-Regulation
18.
Acta Crystallogr Sect E Struct Rep Online ; 66(Pt 2): m213-4, 2010 Jan 30.
Article in English | MEDLINE | ID: mdl-21579675

ABSTRACT

In the crystal structure of the title compound, {[MnNa(C(6)H(4)NO(3))(3)]·H(2)O}(n), the Mn(II) cation is located on a threefold rotation axis and is chelated by three 2-oxidopyridinium-3-carboxyl-ate (opc) anions in an octa-hedal coordination. The Na(I) cation is located on a threefold rotation axis and is surrounded by six O atoms from three opc anions. The opc anions link the Mn and Na cations, forming a three-dimensional polymeric structure. The uncoordinated water mol-ecule, located on a threefold rotation axis, is equally disordered over two sites. The three-dimensional network is consolidated by N-H⋯O hydrogen bonds.

19.
Acta Crystallogr Sect E Struct Rep Online ; 65(Pt 4): m387-8, 2009 Mar 11.
Article in English | MEDLINE | ID: mdl-21582338

ABSTRACT

The title compound, [CoNa(4)(C(8)H(3)O(7)S)(2)(H(2)O)(12)](n), is a three-dimensional coordination polymer bridged by sulfoisophthalate trianions and water mol-ecules. The Co(II) atom, located on an inversion centre, is coordinated by two carboxyl-ate groups of the sulfoisophthalate trianions and by four water mol-ecules in a distorted CoO(6) octa-hedral geometry. Two independent Na(I) atoms also have a distorted octa-hedral coordination geometry formed by water, carboxyl-ate O and sulfonate O atoms. An extensive O-H⋯O and C-H⋯O hydrogen-bonding network is present in the crystal structure, as well as weak π-π stacking [centroid-centroid distance = 3.9553 (11) Å].

20.
Acta Crystallogr Sect E Struct Rep Online ; 65(Pt 4): m429-30, 2009 Mar 25.
Article in English | MEDLINE | ID: mdl-21582369

ABSTRACT

In the crystal structure of the title compound, [Na(4)Ni(C(8)H(3)O(7)S)(2)(H(2)O)(12)](n), the Ni(II) cation occupies an inversion centre and is coordinated by the carboxyl groups of the sulfoisophthalate trianions and water mol-ecules in a distorted octa-hedral geometry. Two independent Na(I) atoms are connected by the carboxyl and sulfonate groups of the sulfoisophthalate ligands anions and water mol-ecules in a distorted octa-hedral geometry. The sulfoisophthalate ligands and coordinated water mol-ecules bridge the Ni(II) and Na(I) cations, forming a three-dimensional polymeric structure. Weak π-π stacking is present between parallel benzene rings [centroid-centroid distance = 3.9349 (10) Å]. Extensive O-H⋯O and C-H⋯O hydrogen bonding helps to stabilize the crystal structure.

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