Chromosome-scale genome assembly provides insights into flower coloration mechanisms of Canna indica.

Canna indica, which produce conspicuous and colorful flowers, are widely appreciated as ornamental plants. We used Pacific Biosciences sequencing (PacBio) and chromosome conformation capture (Hi-C) genome scaffolding to build a high-quality chromosome-scale genome assembly of C. indica and the genome assembly was 821Mb with a contig N50 of 48Mb assembled into nine chromosomes. The genome of C. indica was predicted to contain 31,130 genes and 30,816 genes were functionally annotated. Genome annotation identified 522 Mb (63.59 %) as repetitive sequences. Genome evolution analysis showed that whole-genome duplication occurred 53.4 million years ago. Transcriptome analysis revealed that petal coloration was linked with the expression of genes encoding enzymes involved in anthocyanin biosynthesis, carotenoid biosynthesis, and the methylerythritol phosphate (MEP) pathway. Furthermore, modules of co-expressed genes and hub genes were identified via weighted gene co-expression network analysis. These results suggested that, in Canna indica, deep red petal coloration was regulated by CHS2 and yellow petal coloration was associated with expression of ARF6 and NAC14. Considered together, the current study revealed a high-quality reference genome which may provide new insights into the molecular basis of flower coloration in Canna indica and help enhance the conservation and breeding of ornamental plants in general.

Network analysis and experimental pharmacology study explore the protective effects of Isoliquiritigenin on 5-fluorouracil-Induced intestinal mucositis.

5-fluorouracil (5-FU) is one of the most widely used chemotherapy drugs for malignant tumors. However, intestinal mucositis caused by 5-FU is a severe dose-limiting toxic effect and even leads to treatment interruption. Isoliquiritigenin (ISL) is one of the main active compounds of licorice, which is a traditional Chinese herbal medicine commonly used in inflammation and gastrointestinal diseases. It is speculated that ISL have protective effects on intestinal mucositis. However, no such studies have been reported. Therefore, to investigate the impact of ISL on 5-Fu-induced intestinal mucositis, a strategy based on network prediction and pharmacological experimental validation was proposed in this study. Firstly, the targets and mechanism of ISL in alleviating 5-Fu-induced gastrointestinal toxicity were predicted by network analysis. And the results were further confirmed by molecular docking. Then, a mouse model of intestinal mucositis was established by intraperitoneal injection of 5-FU (384 µmol/kg) to verify the prediction of network analysis. The network analysis results suggested that PTGS2 (Prostaglandin G/H synthase 2) and NOS2 (Nitric oxide synthase, inducible) might be the critical targets of ISL for reducing the intestinal toxicity of 5-FU. In addition, KEGG and GO enrichment analysis revealed that the HIF-1, TNF, MAPK, IL-17, PI3K-Akt, Ras, NF-kappa B signaling pathway, and biological processes of the inflammatory response, apoptosis regulation, NO production and NF-kappa B transcription factor activity might be involved in the mechanism of ISL against intestinal mucositis. Subsequent animal experiments showed that ISL could reduce the weight loss, leukopenia and mucosal damage caused by 5-FU. Compared with the intestinal mucositis model, the protein expressions of PTGS2, NOS2, TNFα (Tumor necrosis factor-alpha) and NF-κB p65 (nuclear factor kappa-B P65) were decreased after ISL treatment. In conclusion, this study is the fist time to find that ISL can attenuate 5-FU-induced intestinal mucositis in mice. Its anti-mucositis effect may be through regulating TNF/NF-κB pathway and inhibiting inflammatory mediators PTGS2 and NOS2. It will provide a potential candidate for the prevention and treatment of chemotherapy-induced intestinal mucositis.

Correlation between fetal cranial nervous system malformation and chromosome abnormality / 中华实用儿科临床杂志

Objective@#To investigate the correlation between fetal cranial nervous system malformation and chromosome abnormality.@*Methods@#The pregnant women with fetal cerebral nervous system dysplasia were collected from January 2013 to August 2018 at the Prenatal Diagnostic Center of the Sixth Affiliated Hospital of Guangzhou Medical University.The fetus was diagnosed by ultrasonography and karyotype analysis.@*Results@#A total of 18 cases of abnormal karyotypes were detected from 85 patient samples, and the abnormal rates were 21.18%.Single cranial nervous system malformation was found in 47 cases, abnormal karyotypes in 4 cases, multiple system malformation in 38 cases, and abnormal karyotypes in 14 cases, and the abnormal karyotype rate of multiple system malformation was higher than that of single cranial nervous malformation (36.84% vs.8.51%, χ2=10.101, P=0.001 5). And the 88.89%(16/18 cases)of abnormal karyotypes were founded in the early and middle pregnancy (≤28 weeks). The abnormal karyotype detection rates of cranial nervous system malformation associated with cardiovascular, skeletal and limb, facial neck abnormalities were 58.82% (10/17 cases), 50.00% (6/12 cases) and 50.00% (9/18 cases), respectively.In the fetal phenotypes, the abnormal karyotype detection rates of choroid plexus cysts were up to 64.29%, followed by arachnoid cysts (50.00%), craniocerebral abnormalities (45.45%) and holoprosencephaly (36.36%).@*Conclusions@#Chromosomal aneuploidy or structural abnormalities can lead to abnormal development of the fetal cranial nervous system, in which the rates of abnormal karyotypes on fetal cranial nervous with cardiovascular malformation and choroid plexus cysts are the highest.

Prenatal diagnosis of a fetus with trisomies of 11q23.3q25 and 22q11.1q11.21 / 中华医学遗传学杂志

OBJECTIVE@#To explore the phenotype and pathogenesis of a fetus with a rare chromosomal abnormality.@*METHODS@#The fetus was analyzed by clinical prenatal ultrasonography, G-banding karyotyping and next generation sequencing (NGS).@*RESULTS@#Prenatal ultrasonography of the fetus showed Dandy-Walker syndrome, growth restriction, and right-heart system dysplasia. The fetus had a chromosomal karyotype of 47,XY,t(11;22)(q23.3;q11.2),+der(22)t(11;22). Duplication of 11q23.3q25 and 22q11.1q21 were also detected by NGS. The chromosomal translocation carried by the fetus was derived from his father.@*CONCLUSION@#Duplications of chromosome 11q23.3q25 and 22q11.1q11.21 segments probably underlie the Dandy-Walker syndrome, growth restriction, and hypoplasia of the right heart system in the fetus.

Correlation between fetal cranial nervous system malformation and chromosome abnormality / 中华实用儿科临床杂志

Objective To investigate the correlation between fetal cranial nervous system malformation and chromosome abnormality.Methods The pregnant women with fetal cerebral nervous system dysplasia were collected from January 2013 to August 2018 at the Prenatal Diagnostic Center of the Sixth Affiliated Hospital of Guangzhou Medical University.The fetus was diagnosed by ultrasonography and karyotype analysis.Results A total of 18 cases of abnormal karyotypes were detected from 85 patient samples,and the abnormal rates were 21.18％.Single cranial nervous system malformation was found in 47 cases,abnormal karyotypes in 4 cases,multiple system malformation in 38 cases,and abnormal karyotypes in 14 cases,and the abnormal karyotype rate of multiple system malformation was higher than that of single cranial nervous malformation (36.84％ vs.8.51％,x2 =10.101,P =0.001 5).And the 88.89％ (16/18 cases) of abnormal karyotypes were founded in the early and middle pregnancy (≤ 28 weeks).The abnormal karyotype detection rates of cranial nervous system malformation associated with cardiovascular,skeletal and limb,facial neck abnormalities were 58.82％ (10/17 cases),50.00％ (6/12 cases) and 50.00％ (9/18 cases),respectively.In the fetal phenotypes,the abnormal karyotype detection rates of choroid plexus cysts were up to 64.29％,followed by arachnoid cysts (50.00％),craniocerebral abnormalities (45.45％) and holoprosencephaly (36.36％).Conclusions Chromosomal aneuploidy or structural abnormalities can lead to abnormal development of the fetal cranial nervous system,in which the rates of abnormal karyotypes on fetal cranial nervous with cardiovascular malformation and choroid plexus cysts are the highest.

High-resolution Mapping of Hyperglycemia-induced Gastric Slow Wave Dysrhythmias

BACKGROUND/AIMS: It is now recognised that gastric dysrhythmias are best characterised by their spatial propagation pattern. Hyperglycemia is an important cause of gastric slow wave dysrhythmia, however, the spatiotemporal patterns of dysrhythmias in this context have not been investigated. This study aims to investigate the relationship between hyperglycemia and the patterns of dysrhythmias by employing high-resolution (multi-electrode) mapping simultaneously at the anterior and posterior gastric serosa. METHODS: High-resolution mapping (8 × 16 electrodes per serosal) was performed in 4 anesthetized hounds. Baseline recordings (21 ± 8 minutes) were followed by intravenous injection of glucagon (0.5 mg per dose) and further recordings (59 ± 15 minutes). Blood glucose levels were monitored manually using a glucose sensing kit at regular 5-minute intervals. Slow wave activation maps, amplitudes, velocity, anisotropic ratio, and frequency were calculated. Differences were compared between baseline and post glucagon injection. RESULTS: Baseline slow waves propagated symmetrically and antegrade. The blood glucose levels were increased by an average of 112% compared to the baseline by the end of the recordings. All subjects demonstrated elevated incidence of slow wave dysrhythmias following injection compared to the baseline (48 ± 23% vs 6 ± 4%, P < 0.05). Dysrhythmias arose simultaneously or independently on anterior and posterior serosa. Spatial dysrhythmias occurred before and persisted after the onset and disappearance of temporal dysrhythmias. CONCLUSIONS: Infusion of glucagon induced gastric slow wave dysrhythmias, which occurred across a heterogeneous range of patterns and frequencies. The spatial dysrhythmias of gastric slow waves were shown to be more prevalent and persisted over a longer period of time compared to the temporal dysrhythmias.

Regulation of autophagy by tea polyphenols in diabetic cardiomyopathy / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

OBJECTIVE@#To investigate the effect of tea polyphenols on cardiac function in rats with diabetic cardiomyopathy, and the mechanism by which tea polyphenols regulate autophagy in diabetic cardiomyopathy.@*METHODS@#Sixty Sprague-Dawley (SD) rats were randomly divided into six groups: a normal control group (NC), an obesity group (OB), a diabetic cardiomyopathy group (DCM), a tea polyphenol group (TP), an obesity tea polyphenol treatment group (OB-TP), and a diabetic cardiomyopathy tea polyphenol treatment group (DCM-TP). After successful modeling, serum glucose, cholesterol, and triglyceride levels were determined; cardiac structure and function were inspected by ultrasonic cardiography; myocardial pathology was examined by staining with hematoxylin-eosin; transmission electron microscopy was used to observe the morphology and quantity of autophagosomes; and expression levels of autophagy-related proteins LC3-II, SQSTM1/p62, and Beclin-1 were determined by Western blotting.@*RESULTS@#Compared to the NC group, the OB group had normal blood glucose and a high level of blood lipids; both blood glucose and lipids were increased in the DCM group; ultrasonic cardiograms showed that the fraction shortening was reduced in the DCM group. However, these were improved significantly in the DCM-TP group. Hematoxylin-eosin staining showed disordered cardiomyocytes and hypertrophy in the DCM group; however, no differences were found among the remaining groups. Transmission electron microscopy revealed that the numbers of autophagosomes in the DCM and OB-TP groups were obviously increased compared to the NC and OB groups; the number of autophagosomes in the DCM-TP group was reduced. Western blotting showed that the expression of LC3-II/I and Beclin-1 increased obviously, whereas the expression of SQSTM1/p62 was decreased in the DCM and OB-TP groups (P<0.05).@*CONCLUSIONS@#Tea polyphenols had an effect on diabetic cardiomyopathy in rat cardiac function and may alter the levels of autophagy to improve glucose and lipid metabolism in diabetes.

Prevalence and genotype distribution of human papillomavirus in 961,029 screening tests in southeastern China (Zhejiang Province) between 2011 and 2015.

Human papillomavirus infection plays a key role in the development of cervical cancer. To establish a foundation for HPV-based screening and vaccination programs, we investigated the HPV prevalence and genotypic distributions in Chinese women from Zhejiang Province. Between 2011 and 2015, a total of 961,029 samples from 2021 clinical hospitals were tested HPV genotype by a PCR-based hybridization gene chip assay, and 443,890 samples were evaluated cervical cytology by liquid-based cytology analysis. Our results showed that the positive rate for HPV was 20.54%, which ranged from 28.72% to 17.81% and varied by year of recruitment. Age-specific prevalence showed a "two-peak" pattern, with the ≤20-year-old group presenting the highest HPV infection rate, followed by 61-70-year-old group. Overall, the most prevalent genotypes were HPV16, 52 and 58. Additionally, the odds ratios for the prevalence of the HR-HPV, LR-HPV and HPV-negative groups with abnormal cytology were 12.56, 3.21 and 0.06, respectively. Among genotypes, HPV 16 has been found to have the highest OR, followed by HPV58, 18, 52. Here, we present data regarding the prevalence and type distribution of HPV infection, which can serve as valuable reference to guide nationwide cervical cancer screening and HPV vaccination programs.

The Role of Cytokines in the Peripheral Blood of Major Depressive Patients.

BACKGROUND: Recent technological advances offer an opportunity to further elucidate the complex cytokine network in Major Depressive Disorder (MDD). The objective of this study was to investigate the role of pro-inflammatory and anti-inflammatory cytokines in the mechanism of depressive disorders. Given the activating role of cytokines on the hypothalamic-pituitary-adrenal (HPA) axis, and the relevance of its regulation in MDD, we also analyzed the relationships between several cytokines and cortisol levels. METHODS: Twenty-five unipolar depressive patients and 20 healthy controls were recruited in this study. Flow cytometric bead array system (FCM-CBA) was used to examine the concentration of cytokines (IL-2, IL-4, IL-6, IL-10, TNF, INF-α) in peripheral blood. Plasma Adrenocorticotropic Hormone (ACTH) and serum cortisol concentrations were detected. RESULTS: Compared with the controls, depressive patients had a significant increase in concentration of IL-2, TNF, serum cortisol, and TNF/IL-4 (p < 0.05). There was a significant positive correlation between serum cortisol and IL-2, as well as ACTH and IL-2 (p < 0.05) in depressive patients. There was a significant positive correlation between IL-2 and the Hamilton depression rating scale (HAMD) total scores in depressive patients, and also with TNF (p < 0.05). There was no significant difference in concentration of IL-4, IL-6, IL-10, and INF-α between two groups (p > 0.05). CONCLUSIONS: The present results suggest that depressive patients had an increase in concentration of some pro-inflammatory cytokines. Both IL-2 and TNF play important roles in the development of depressive disorders, and their concentration in peripheral blood may be used to evaluate the severity of depressive disorders.

The effects of microRNAs on glucocorticoid responsiveness.

PURPOSE: Glucocorticoids (GCs) are of wide usage in the clinical treatment of lymphoblastic malignancies such as acute lymphoblastic leukemia. However, individually distinctive responsiveness to the GC therapy may attenuate their clinical efficacy, and more reliable predictor for GC resistance is still eagerly needed. Recent studies indicate that microRNAs (miRNAs), which demonstrate regulatory functions targeting mRNAs during the post-transcription, involved in the regulation of GCs sensitivity through several mechanisms, especially adjusting the magnitude of GC receptors (GRs), which mediates the cellular effects of GCs and plays a pivotal role in GCs sensitivity, inspiring that special miRNAs pattern could serve as the biomarkers to predict GC sensitivity and bring forth potential strategies for overcoming drug resistance. In this review, we discuss related miRNAs and their diverse effects exerted on multifaceted complexity of GCs responsiveness for further exploiting the molecular mechanism of GC resistance and future construction of the molecular diagnostic method and reverse GC resistance. METHODS: We have reviewed and searched for eligible literature relating to the effects of microRNAs on GC responsiveness from systematic PubMed searches. RESULTS: GC response can be mediated by miRNAs through influence on GC signaling pathway, leading to diverse glucocorticoid responsiveness. Mutations in miRNA gene also influence GC response. As well, GCs regulate the function of several miRNAs, and suggesting a bidirectional influence among them. CONCLUSIONS: It is possible and necessary that miRNAs serve as stable biomarkers and GC resistant patients would benefit from an effective and early screening test.

MicroRNA-185-5p restores glucocorticoid sensitivity by suppressing the mammalian target of rapamycin complex (mTORC) signaling pathway to enhance glucocorticoid receptor autoregulation.

Overexpression of microRNA-185-5p (miR-185-5p) in glucocorticoid (GC)-sensitive acute lymphoblastic leukemia (ALL) was identified using a microarray and reverse transcription polymerase chain reaction and was further confirmed in ALL cell lines. A reporter assay confirmed that the Rictor-one component of mammalian target of rapamycin complex 2 (mTORC2) is a target of miR-185-5p. Decreased mTORC activity was also confirmed in GC-sensitive patients. Overexpression of miR-185-5p significantly enhanced GC sensitivity in CEM-C1 cells (GC resistance) by increasing the rate of cell apoptosis and cycle arrest, and decreasing cell survival, accompanied by a decrease in mTORC activity and an increase in GC-induced glucocorticoid receptor (GR) expression. Rapamycin, an mTORC1 inhibitor, showed similar effects to miR-185-5p. These results demonstrated that miR-185-5p enhances GC sensitivity via suppression of mTORC activity by enhancing GR autoupregulation and that miR-185-5p is a potential target for the diagnosis and reversion of GC resistance.

Effects of dimethyltin chloride on renal H~+K~+-ATPase and Na~+K~+-ATPase activity in rats / 中国职业医学

OBJECTIVE: To study the effects of dimethyltin chloride( DMT) on the activity of renal H~+K~+-ATPase( HKA)and Na~+K~+-ATPase( NKA) in SD rats. METHODS: i) In vitro experiment. Five specific pathogen free( SPF) healthy female SD rats were used. The kidney homogenates made with 0. 90% sodium chloride solution was added with DMT( mass concentration,1. 0 g/L) to make final concentrations of 0,1,25,125 and 625 mg/L respectively,then the HKA and NKA activities were detected by the enzyme-linked immunosorbent assay( ELISA). ii) In vivo experiment. Forty SPF healthy SD rats were divided into control group and exposure group,with 20 rats( 10 males and 10 females) in each group. The exposure group was given one-time intraperitoneal injection with DMT( 16. 000 mg / kg body weight),while the control group was given one-time intraperitoneal injection with same volume of 0. 90% sodium chloride solution. The rats were executed 1 and 24 hours after exposure. The kidney tissue was extracted to make kidney homogenates for determination of HKA and NKA activity by microplate reader. The blood from abdominal aorta was collected to measure the levels of serum K~+,Na~+and Cl-. RESULTS: i) In vitro experiment. The HKA activity was inhibited by DMT,and the effect of inhibition increased with the increase of DMT exposure dose( P < 0. 01),showing a dose-effect relationship. The DMT had no effect on NKA activity( P > 0. 05). ii) In vivo experiment. The body weight of rats at 24 hours time point in exposed group was lower than that in control group( P < 0. 01). The HKA activity of the kidney tissue in rats in exposed group was lower than that of control group( P < 0. 01). The NKA activity in kidney tissue of rats and the level serum K~+,Na~+and Cl-did not show statistical difference in main and interactive effects concerning treatment and exposure time( P > 0. 05). CONCLUSION: DMT could inhibit the HKA activity in kidney homogenates,but had no obvious effect on NKA activity.

Cell atavistic transition: Paired box 2 re-expression occurs in mature tubular epithelial cells during acute kidney injury and is regulated by Angiotensin II.

The regeneration of tubular epithelial cells (TECs) after acute kidney injury (AKI) is crucial for the recovery of renal structure and function. The mechanism by which quiescent TECs re-obtain a potential to regenerate remains unknown. In this study, we observed a transient re-expression of embryonic gene Paired box 2 (Pax2) in adult rat TECs in vivo during ischemia-reperfusion induced AKI and most Pax2 positive TECs co-expressed kidney injury molecule-1 (KIM-1), a tubular injury marker. The re-expression of Pax2 was accompanied by increased levels of intrarenal Angiotensin II, which is a crucial injury factor of AKI. Furthermore, we also found a temporary re-expression of Pax2 in NRK-52E cells under the stimulation of Angiotensin II. This stimulatory effect could be blocked by PD123319 (Angiotensin II type 2 receptor (AT2R) inhibitor) and AG490 (Janus Kinase 2 (JAK2) inhibitor). As Pax2 is essential for the phenotypic conversion from mesenchymal stem cells to TECs during kidney development, we proposed that the re-expression of Pax2 in mature TECs may be an indicator of "atavistic" transition which mimics but reverses the processes of development of TECs. This could be proved by that a progenitor marker, CD24, was also found to be transiently expressed shortly after the expression of Pax2 in NRK-52E cells stimulated with Angiotensin II. The expression of CD24 was also suppressed by PD123319 and AG490. Moreover, knockdown of Pax2 by RNA interference could significantly reduce the expression of CD24 in NRK-52E cells stimulated with Angiotension II. Those findings suggest that mature TECs can trans-differentiate into progenitor-like cells by "atavistic transition", which may participate in the recovery of tissue structure and Pax2 may play a pivotal role in this process. That might have important implications for further understanding of tubular regeneration after injury.

Loss of polycystin-1 inhibits Bicc1 expression during mouse development.

Bicc1 is a mouse homologue of Drosophila Bicaudal-C (dBic-C), which encodes an RNA-binding protein. Orthologs of dBic-C have been identified in many species, from C. elegans to humans. Bicc1-mutant mice exhibit a cystic phenotype in the kidney that is very similar to human polycystic kidney disease. Even though many studies have explored the gene characteristics and its functions in multiple species, the developmental profile of the Bicc1 gene product (Bicc1) in mammal has not yet been completely characterized. To this end, we generated a polyclonal antibody against Bicc1 and examined its spatial and temporal expression patterns during mouse embryogenesis and organogenesis. Our results demonstrated that Bicc1 starts to be expressed in the neural tube as early as embryonic day (E) 8.5 and is widely expressed in epithelial derivatives including the gut and hepatic cells at E10.5, and the pulmonary bronchi at E11.5. In mouse kidney development, Bicc1 appears in the early ureteric bud and mesonephric tubules at E11.5 and is also expressed in the metanephros at the same stage. During postnatal kidney development, Bicc1 expression gradually expands from the cortical to the medullary and papillary regions, and it is highly expressed in the proximal tubules. In addition, we discovered that loss of the Pkd1 gene product, polycystin-1 (PC1), whose mutation causes human autosomal dominant polycystic kidney disease (ADPKD), downregulates Bicc1 expression in vitro and in vivo. Our findings demonstrate that Bicc1 is developmentally regulated and reveal a new molecular link between Bicc1 and Pkd1.

The value of heart-type fatty acid binding protein in the early diagnosis of acute myocardial infarction in elderly patients / 中华老年医学杂志

Objective To investigate the diagnostic value of heart-type fatty acid binding protein (H-FABP) versus cardiac trofonin I (cTnI) and creatinekinase-MB (CK-MB) in early diagnosis of acute myocardial infarction (AMI) in elderly patients.Methods 67 patients with acute chest pain were selceted sequentially and divided into AMI group (n＝30) and non-AMI group (n=37).Plasma H-FABP level was rapidly detected by using colloidal gold reagent plate and solid phase immunochromatographic assay for qualitative determination within and after 6 hours of AMI onset.Plasma levels of cTnI and CK-MB were determined within and after 6 hours of onset.The diagnositic value of H-FABP,cTnI and CK-MB in AMI was compared within and after 6 hours of onset.Results The sensitivity of H-FABP was better than that of cTnI and CK-MB within 6 hours of onset (93.3％ vs.46.6％,23.3％,both P＜0.05).The negative predictive value of H-FABP was better than that of cTnI and CK-MB within 6 hours of onset (94.7％ vs.69.8％,61.1％,both P＜ 0.05) While,positive predictive value and specificity were basically the same between H-FABP,versus cTnI and CK-MB.H-FABP and cTnI levels had significant differences between AMI and non AMI group after 6 hours of onset (all P＜0.05).Plasma levels of cTnl and CK-MB were higher after 6 hours than within6 hours [cTnI (4.10±1.79) mg/L vs.(1.45±1.31) mg/L,CK MB(180.52± 158.70) U/L vs.(20.02± 7.97) U/L,both P＜0.05].Conclusions As compared with cTnI and CK-MB,within 6 hours after AMI onset,H-FABP as a new myocardial necrosis marker has higher sensitivity,specificity,positive and negative predictive values in the diagnosis of AMI.While,after 6 hours of AMI onset,H-FABP has the same diagnostic value as cTnI and CK-MB.

Nuclear HSP90 regulates the glucocorticoid responsiveness of PBMCs in patients with idiopathic nephrotic syndrome.

Resistance to glucocorticoid (GC) is a challenge for the treatment of patients with idiopathic nephrotic syndrome (INS). Most of the effects of GC are mediated by the GC receptor (GR). Heat shock protein 90 (HSP90) is an important molecular chaperone for the GR and is supposed to be the key factor in regulating GC effects. In a previous study, we found that both the expression and nuclear distribution of HSP90 were increased in GC resistant INS patients. The aim of this study is to explore how these phenomena contribute to GC resistance in INS patients. Healthy subjects and INS patients with different GC responses were recruited. The total HSP90 expression was determined by reverse transcription-PCR and flow cytometric analysis. Western blot analysis was used to evaluate the expression of nuclear HSP90. Co-immunoprecipitation and electrophoretic mobility gel shift assays were performed to explore the interaction between HSP90 and the GR in the nucleus as well as the DNA-binding activity of GR. We induced the upregulation of the expression of total HSP90 in PBMCs by treatment with interleukin-6 in vitro and found that the nuclear HSP90 level, the DNA-binding activity of the GR and the cell apoptotic responsiveness to GC remained unchanged. Furthermore, an increased nuclear HSP90 was demonstrated mainly by binding to GR in the nucleus, while the DNA-binding activity of the GR dramatically decreased in GC resistant INS patients. The present results suggest that the accumulation of HSP90 in the nucleus potentially hinders DNA-binding activity and transactivation, which may contribute to GC resistance in patients with INS.

WT1 and Pax2 re-expression is required for epithelial-mesenchymal transition in 5/6 nephrectomized rats and cultured kidney tubular epithelial cells.

Mature tubular epithelial cells in the adult kidney can undergo epithelial-mesenchymal transition (EMT), a phenotypic change that is linked to the pathogenesis of renal interstitial fibrosis. EMT may be considered the reverse of mesenchymal-epithelial transition, which occurs during normal kidney development. The Wilms' tumor suppressor gene WT1 and the paired box 2 gene Pax2 are needed to induce mesenchymal-epithelial transition and play key roles in the progression of nephrogenesis. However, until now, WT1 and Pax2 have not been tested for their direct involvement in the process of renal tubular EMT. In this study, we explored the potential roles of WT1 and Pax2 in EMT that is induced in the remnant kidney of rats following 5/6 nephrectomy. We also examined WT1 and Pax2 in cultured renal tubular epithelial (NRK52E) cells treated with interleukin-1α and investigated the effects of blocking EMT using RNA interference. We showed that WT1 and Pax2 were re-expressed in the EMT models, and these were accompanied by decreased expression of E-cadherin and increased expression of vimentin, Snail and α-smooth muscle actin. Silencing WT1 and Pax2 by RNA interference blocked the interleukin-1α-induced EMT in the NRK52E cells, as reflected in the suppression of α-SMA and Snail expression, the restoration of E-cadherin expression and normal cell morphology. Our experiments suggested that the re-expression of WT1 and Pax2 in the tubular epithelial cells plays important roles in the promotion of EMT, and there may be therapeutic value in silencing Pax2 and WT1 to prevent or reverse renal fibrosis.

The roles and administration methods of insulin in the early treatment of acute brain injury / 中国医师杂志

Objective To explore the roles of insulin in the early treatment of acute brain injury and its administration methods.Methods 253 patients were randomly divided into the intensive insulin therapy group and the conventional therapy group.Infection rates,the short-term effect (APACHE Ⅱ assessment),and long-term efficacy (GOS prognosis) was compared between two groups.Results The results of the strengthen treatment group in the rate of infection (25.95％ vs 39.34％,x2 =5.17,P ＜0.05),the short-term effect (11.33 ± 7.66 vs 16.49 ± 14.97,u =3.42,P ＜ 0.05) and the long-term efficacy (40.46％,55.73％,3.82％ vs 25.41％,68.85％,5.74％,x2 =7.62,P ＜0.05) were significantly better than the conventional therapy group with the statistically significant differences (P ＜ 0.05).Conclusions The hypoglycemic effect,neuroprotective effect,regulatory role,and nutrition role of insulin occurred in the early treatment of acute brain injury.After acute brain injury,patients with hyperglycemia should be treated early with an enough volume,continuous,and uniform insulin.