Effects of movement training based on rhythmic auditory stimulation in cognitive impairment: a meta-analysis of randomized controlled clinical trial.

Objective: According to the World Alzheimer's Disease Report in 2015,there were 9.9 million new cases of dementia in the world every year. At present, the number of patients suffering from dementia in China has exceeded 8 million, and it may exceed 26 million by 2040.Mild cognitive impairment (MCI) refers to the pathological state of pre-dementia with the manifestation of the progressive decline of memory or other cognitive functions but without decline of activities of daily life. It is particularly important to prevent or prolong the development of MCI into dementia. Research showing effects of rhythmic auditory stimulation based-movement training(RASMT) interventions on cognitive function is also emerging. Therefore, the present meta-analysis briefly summarize findings regarding the impacts of RASMT programs on cognitive impairment. Methods: Data from Pubmed, Embase, and Cochrane Library were utilized. The impact of RASMT on cognitive functions was evaluated using indicators such as overall cognitive status, memory, attention, and executive functions. The REVMAN5.3 software was employed to analyze bias risks integrated into the study and the meta-analysis results for each indicator. Results: A total of 1,596 studies were retrieved, of which 1,385 non-randomized controlled studies and 48 repetitive studies were excluded. After reviewing titles and abstracts of the remaining 163 articles, 133 irrelevant studies were excluded, 30 studies were downloaded and read the full text. Among 30 articles, 18 articles that did not meet the inclusion criteria were excluded, the other 12 studies were included in this meta-analysis. Utilizing the Cochrane Collaborative Network Bias Risk Assessment Scale, it was found that 11 studies explained the method of random sequence generation, nine studies did not describe allocation concealment, four were single-blinded to all researchers, and eight reported single-blinding in the evaluation of experimental results. In the meta-analysis, the main outcomes showed statistically significant differences in overall cognitive status [MD = 1.19, 95%CI (0.09, 2.29), (p < 0.05)], attention [MD = -1.86, 95%CI (-3.53, -0.19), (p < 0.05)], memory [MD = 0.71, 95%CI (0.33, 1.09), (p < 0.01)], and executive function [MD = -0.23, 95% CI (-0.44, -0.02), (p < 0.05)]. Secondary outcomes indicated no statistically significant differences in verbal fluency [MD = -0.51, 95%CI (-1.30, 0.27), (p = 0.20)], while depression [MD = -0.29, 95% CI (-0.42, -0.16), (p < 0.01)] and anxiety [MD = 0.19, 95% CI (0.06, 0.32), (p < 0.01)] exhibited statistically significant differences. The GRADEpro GDT online tool assessed the quality of evidence for the outcome measures, revealing one low-quality outcome, two moderate-quality outcomes, and one high-quality outcome in this review. Conclusion: This study shows that RASMT can improve the general cognitive status, memory, attention and executive function of patients with cognitive impairment. The quality of evidence revealed that MMSE was low, attention and memory were moderate, and executive function was high. The RAMST program (type of exercise: play percussion instruments; time of exercise: 30-60 min; frequency of exercise: 2-3 times/week; duration of exercise: more than 12 weeks) was proved to be more effective in improving cognitive function. However, the sample size is relatively insufficient, the future needs further study. Systematic review registration: PROSPERO, identifier: CRD42023483561.

Development and Application Evaluation of a Nursing Simulation Teaching Information System Based on Hospital Information Systems.

Background: The extensive application of hospital information systems in the current information-driven era suggests that nursing education should focus on information education. Methods: The newly developed hospital information system was used and evaluated by 544 students to explore the feasibility and necessity of such applications for teaching. Results: Overall, 97.1% of the students expressed satisfaction, and 96.0% supported simulated information education for nursing. The usability was good, with the system receiving a usability score of 72.625 ± 13.0907. The junior students had a higher score than the sophomores regarding system availability, and the difference was statistically significant. Conclusions: Students generally had a high degree of satisfaction with the simulated information nursing education system and highly approved of the teaching method. However, the system needs to be upgraded.

Surgical Treatment of Pineal Region Tumors: An 18 year-Experience at a Single Institution.

BACKGROUND: The pineal tumor was once considered as a restricted area for surgery. Such cases are rare, with many different opinions on surgical treatment. This study aimed to review our experience of tumor treatment in the pineal region and explore the optimal treatment strategy. METHODS: The clinical data of 72 patients with pineal tumors from January 1997 to May 2015 (18 years) were retrospectively analyzed. Preoperative preparation, pathology type, tumor resection rate, surgical approach, and follow-up outcomes were used as the indicators to evaluate the treatment efficacy. RESULTS: The Krause approach was used in 46 cases, the Poppen approach in 10 cases, and the transcallosal-lateral ventricle-choroid fissure approach in 16 cases. The postoperative pathological results were as follows: 24 cases of germinoma, 11 of teratoma, 15 of glioma, 6 of meningioma, 11 of Pineocytoma, 2 of cholesteatoma, 2 of cavernous hemangioma, and 1 of choriocarcinoma. Further, the study included 64 cases of total surgical resections, 8 of subtotal resections, and 2 deaths. The follow-up period was from 7 months to 10 years. Further, 51 (70.8%) patients were followed up. The multivariate regression model showed that the surgical method and the pathological type contributed significantly to predicting outcomes. CONCLUSIONS: The type of pathology, extent of excision, and surgical approach had a significant impact on the prognosis of patients. The transcallosal-lateral ventricle-choroid fissure approach for large and medium-sized pineal tumors near the posterior part of the third ventricle had good efficacy.

The value of ultrasound guided laser ablation in papillary thyroid recurrence carcinoma: A retrospective, single center study from China.

Objective: The efficacy and safety of ultrasound-guided percutaneous laser ablation (PLA) for treating recurrent papillary thyroid cancer nodules (RPTCNs). Methods: A retrospective study was conducted in 43 patients with single recurrent thyroid cancer which was diagnosed by fine needle aspiration biopsy (FNAB). The extent of ablation was assessed by contrast-enhanced ultrasound (CEUS) 24h after PLA. At baseline (before ablation), 6, and 12 months, and every 6 months thereafter, the following were recorded: nodule maximum diameter, volume reduction rate (VRR), complications, and side effects. Result: All 43 patients were successfully treated with PLA without serious complications. All patients underwent CEUS 24 hours after PLA treatment, and all achieved complete ablation. The success rate of single ablation was 100%. The average follow-up time was 23.47 ± 6.50 months, 12 ~ 36 months. At the last follow-up, 32 (74.4%) ablation lesions disappeared completely and 11 (25.6%) ablation lesions showed scar-like changes. No lymph node metastasis was found during follow-up. The maximum diameter and volume of nodules decreased from 5.1 ± 1.4 mm, 86.22 ± 20.46 mm3 before operation to 0.73 ± 1.1 mm, 1.02 ± 1.92 mm3 at the end of observation (P < 0.01). The average volume reduction rates (VRR) at 6, 12, 18, 24, 30 and 36 months after ablation were 11.92%, 60.64%, 82.26%, 90.96%, 93.7% and 97.79% respectively. No regrowth of treated nodule and distant metastases were detected. One patient (2.3%) had local recurrence and was treated with PLA again. Conclusion: Ultrasound-guided PLA appears to be effective and safe for treating unifocal RPTCNs in selected patients who are ineligible for surgery, which is suitable for clinical application and promotion.

Five new phloroglucinol derivatives from Syzygium brachyantherum and their α-glucosidase and PTP1B inhibitory activities.

Five new phloroglucinol derivatives were isolated from Syzygium brachyantherum, and their structures were elucidated as brachyanones A-E (1-5) on the basis of the extensive spectroscopic analysis. Among them, compounds 1 and 3 exhibited significant inhibitory activity against α-glucosidase with IC50 of 2.57 and 0.97 µM, respectively. Furthermore, compound 4 showed protein tyrosine phosphatase 1B (PTP1B) inhibitory effect with inhibition ratio of 89.42% at 100 µM. This discovery indicates that phloroglucinol derivatives with long aliphatic chain possibly play an important role in antidiabetic activity of Syzygium plants, and they could function as a promising antidiabetic agent.

CircRNA EPHB4 modulates stem properties and proliferation of gliomas via sponging miR-637 and up-regulating SOX10.

Gliomas are the most common type of primary brain tumors. CircRNA ephrin type-B receptor 4 (circEPHB4) is a circular RNA derived from the receptor tyrosine kinase EPHB4. However, the clinical significance and the specific roles of circEPHB4 in gliomas and glioma cancer stem cells (CSC) have not been studied. Here, we found that circEPHB4 (hsa_circ_0081519) and SOX10 were up-regulated and microRNA (miR)-637 was down-regulated in glioma tissues and cell lines. Consistently, circEPHB4 was positively correlated with SOX10 but negatively correlated with miR-637. The altered expressions of these molecules were independently associated with overall survival of patients. CircEPHB4 up-regulated SOX10 and Nestin by directly sponging miR-637, thereby stimulating stemness, proliferation and glycolysis of glioma cells. Functionally, silencing circEPHB4 or increasing miR-637 levels in glioma cells was sufficient to inhibit xenograft growth in vivo. In conclusion, the circEPHB4/miR-637/SOX10/Nestin axis plays a central role in controlling stem properties, self-renewal and glycolysis of glioma cells and predicts the overall survival of glioma patients. Targeting this axis might provide a therapeutic strategy for malignant gliomas.

Bismuth chelate as a contrast agent for X-ray computed tomography.

BACKGROUNDS: Due to the unexpected side effects of the iodinated contrast agents, novel contrast agents for X-ray computed tomography (CT) imaging are urgently needed. Nanoparticles made by heavy metal elements are often employed, such as gold and bismuth. These nanoparticles have the advantages of long in vivo circulation time and tumor targeted ability. However, due to the long residence time in vivo, these nanoparticles may bring unexpected toxicity and, the preparation methods of these nanoparticles are complicated and time-consuming. METHODS: In this investigation, a small molecular bismuth chelate using diethylenetriaminepentaacetic acid (DPTA) as the chelating agent was proposed to be an ideal CT contrast agent. RESULTS: The preparation method is easy and cost-effective. Moreover, the bismuth agent show better CT imaging for kidney than iohexol in the aspect of improved CT values. Up to 500 µM, the bismuth agent show negligible toxicity to L02 cells and negligible hemolysis. And, the bismuth agent did not induce detectable morphology changes to the main organs of the mice after intravenously repeated administration at a high dose of 250 mg/kg. The pharmacokinetics of the bismuth agent follows the first-order elimination kinetics and, it has a short half-life time of 0.602 h. The rapid clearance from the body promised its excellent biocompatibility. CONCLUSIONS: This bismuth agent may serve as a potential candidate for developing novel contrast agent for CT imaging in clinical applications.

Long non-coding RNA GAS5, by up-regulating PRC2 and targeting the promoter methylation of miR-424, suppresses multiple malignant phenotypes of glioma.

PURPOSE: Malignant gliomas remain significant challenges in clinic and pose dismal prognosis on patients. In this study, we focused on growth arrest-specific 5 (GAS5), a tumor suppressive long non-coding RNA in glioma, explored its crosstalk with miR-424, and examined their biological functions in glioma. METHODS: Expressions of GAS5 and miR-424 were measured using qRT-PCR. The regulation of GAS5 on miR-424 expression was examined in GAS5-overexpressing glioma cells by combining methylation-specific PCR, western blotting, and RNA immunoprecipitation. Functional significance of GAS5 and miR-424 on in vitro cell proliferation, apoptosis, migration, invasion, and in vivo tumor growth was examined using colony formation, flow cytometry, wound healing, transwell assay, and the xenograft model, respectively. The potential targeting of AKT3 by miR-424 was investigated using luciferase reporter assay. RESULTS: GAS5 and miR-424 were significantly down-regulated in glioma cells. GAS5 directly interacted with enhancer of zeste homolog 2 (EZH2), stimulated the formation of polycomb repressive complex 2 (PRC2), reduced the levels of DNA methyltransferases (Dnmts), alleviated promoter methylation of miR-424, and promoted miR-424 expression. Functionally, GAS5, by up-regulating miR-424, inhibited cell proliferation, migration, and invasion, while increased apoptosis of glioma cells in vitro, and suppressed xenograft growth in vivo. miR-424 directly inhibited AKT3 and altered the expressions of AKT3 targets, cyclinD1, c-Myc, Bax, and Bcl-2, which might contribute to its tumor suppressive activities. CONCLUSIONS: GAS5, by inhibiting methylation and boosting expression of miR-424, inhibits AKT3 signaling and suppresses multiple malignant phenotypes. Therefore, stimulating GAS5/miR-424 signaling may benefit the treatment of glioma.

The use of amphiphilic copolymer in the solid dispersion formulation of nimodipine to inhibit drug crystallization in the release media: Combining nano-drug delivery system with solid preparations.

Solid dispersion is a widely used method to improve the dissolution and oral bioavailability of water-insoluble drugs. However, due to the strong hydrophobicity, the drug crystallization in the release media after drug dissolution and the resulted decreased drug absorption retards the use of solid dispersions. It is widely known that the amphiphilic copolymer can encapsulate the hydrophobic compounds and help form stable nano-dispersions in water. Inspired by this, we tried to formulate the solid dispersion of nimodipine by using amphipathic copolymer as one of the carriers. Concerning the solid dispersions, there are many important points involved in these formulations, such as the miscibility between the drug and the carriers, the storage stability of solid dispersions, the dissolution enhancement and so on. In this study, a systemic method is proposed. In details, the supersaturation test and the glass transition temperature (Tg) measurement to predict the crystallization inhibition, the ratios of different components and the storage stability, the interactions among the components were investigated in detail by nuclear magnetic resonance (1H NMR) and isothermal titration calorimetry (ITC) and, the final dissolution and oral bioavailability enhancement. It was found that the amphiphilic copolymer used in the solid dispersion encouraged the formation the drug loading micelles in the release media and, finally, the problem of drug crystallization in the dissolution process was successfully solved.

Value of dynamic plasma cell-free DNA monitoring in septic shock syndrome: A case report.

BACKGROUND: Mortality due to septic shock is relatively high. The dynamic monitoring of plasma cell-free DNA (cfDNA) can guide the treatment of septic shock. CASE SUMMARY: Herein, we present a typical case of septic shock syndrome caused by the bacilli Acinetobacter baumannii and Pantoea. The patient complained of abdominal pain, fever and chills upon admission to the Emergency Department. Marked decreases in white blood cells and procalcitonin (PCT) were observed after the patient received continuous renal replacement and extracorporeal membrane oxygenation. Plasma cfDNA levels were consistently high, peaking at 1366.40 ng/mL, as measured by a duplex real-time PCR assay with an internal control, which was developed as a novel method for the accurate quantification of cfDNA. The patient died of septic shock on HD 8, suggesting that cfDNA could be used to monitor disease progression more effectively than PCT and the other inflammatory factors measured in this case. CONCLUSION: CfDNA may be a promising marker that complements other inflammatory factors to monitor disease progression in patients with septic shock.

Comparisons of microbiological characteristics and antibiotic resistance of Klebsiella pneumoniae isolates from urban rodents, shrews, and healthy people.

BACKGROUND: The comparisons of molecular characterization and antibiotic resistance of Klebsiella pneumoniae (KP) isolates from humans and other animal hosts are not well studied. Our goal was to compare the molecular epidemiology of KP strains that were isolated from urban rodents, shrews, and healthy people. RESULTS: K. pneumoniae (KP) isolates were isolated from fecal samples of rodents, shrews and healthy adults in 2015 in southern China. In total, 465 fecal samples were collected, of which 85 from rodents, 105 from shrews, and 275 from healthy adults. Antimicrobial susceptibility and production of extended-spectrum ß-lactamases (ESBL) of the isolates were tested. PCR-based methods were used to detect specific genes, including ESBL genes (blaTEM, blaSHV, and blaCTX-M) in ESBL-producing isolates, capsular serotypes (K1, K2, K5, K20, K54, and K57) in hypervirulent KPs (hvKPs), and virulence genes (magA, wcaG, rmpA, uge, kfu, and aerobactin) in hvKP isolates. Multilocus sequence type (MLST) and pulsed-field gel electrophoresis (PFGE) were performed to exclude the homology of these isolates. The carriage rate of KP in urban rodents and shrews (78.42%) was higher than that in healthy adults (66.18%) (χ2 = 8.206, P = 0.004). The prevalence rates of ESBL-producing isolates among rodents, shrews, and humans were 7.94, 12.79, and 17.03%, respectively. The positive rates of CTX-M, TEM and SHV types in ESBL-producing isolates were 29.79, 27.66, and 17.02%, respectively. Serotype K1, K5, K20, and K57 were detected in both small mammals and humans. PFGE typing revealed thirty-six clusters. PFGE cluster A was clustered by samples of shrews and healthy adult, with a similarity of 88.4%. MLST typing revealed thirty-eight types. ST23 and ST35 were detected in samples of shrews and healthy adults. ST37 was detected in samples of 2 rodents and a healthy adult. CONCLUSIONS: Overlapping serotypes of hvKP were observed in both the animals and humans. The same PFGE or MLST types were also found in isolates derived humans, rodents and shrews. Therefore, urban rodents and shrews might play a certain role in the transmission of drug-resistant and hypervirulent KP.

Synthesis and antitumor evaluation of neolaxiflorin B inspired compounds.

BACKGROUND: Neolaxiflorin B is derived from ent-kaurane like laxiflorin J and eriocalyxin B with a relatively low potency as an antitumor agent. During preliminary structure-activity relationship studies, the α,ß-unsaturated ketone (enone) system is an important active group. METHODS: Seven neolaxiflorin B derivatives containing α,ß-unsaturated ketone moieties were synthesized. In vitro, activity was evaluated against three human tumor cell lines and a rat myogenic cell line (HepG2, NSCLC-H292, SNU-1040, and L6, respectively) by MTT assay. RESULTS: Compound 15 appeared a promising antitumor lead due to its cytotoxic potency and relatively high selectivity, with an SI value of 13.14. Flow cytometry analysis was conducted to show that NSCLC-H292 cells were blocked in the G0/G1 phase in the presence of compound 15, thus inhibiting the proliferation of tumor cells. CONCLUSION: This study has revealed that compound 15 is a promising antitumor lead due to the cytotoxic potencies and the high selectivity it displayed when compared to natural counterparts.

Synthesis of Novel ent-Kaurane-Type Diterpenoid Derivatives Effective for Highly Aggressive Tumor Cells.

We have designed and synthesized 6 ent-Kaurane-type diterpenoid derivatives containing α,ß-unsaturated ketone moieties. In vitro, activity was evaluated against three human tumor cell lines and a rat myogenic cell line (HepG2, NSCLC-H292, SNU-1040, L6) by MTT assay. All the tested compounds exhibited comparable or higher activity than DDP and eriocalyxin B. Compounds 16, 17 and 18 are promising anti-tumor leads due to their cytotoxic potencies and higher selectivity, with SI values of 161.06, 47.80 and 128.20, respectively.

Effects of Fibronectin 1 on Cell Proliferation, Senescence and Apoptosis of Human Glioma Cells Through the PI3K/AKT Signaling Pathway.

BACKGROUND/AIMS: The current study aimed to investigate the role by which fibronectin 1 (FN1) influences the cell cycle, senescence and apoptosis in human glioma cells through the PI3K/ AKT signaling pathway. METHODS: Differentially expressed genes (DEGs) were identified based on gene expression data (GSE12657, GSE15824 and GSE45921 datasets) and probe annotation files from Gene Expression Omnibus. The DEGs were identified in connection with gene ontology (GO) enrichment analysis and with the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The positive expression of the FN1 protein was detected by immunohistochemistry. The glioma cell lines U251 and T98G were selected and assigned into blank, negative control (NC) and siRNA-FN1 groups. A dual luciferase reporter gene assay was used to investigate the effects of FN1 on transcriptional activity through the PI3K/AKT signaling pathway. An MTT assay was applied for the detection of cell proliferation, while flow cytometry was employed for cell cycle stage and cellular apoptosis detection. ß-galactosidase staining was utilized to detect cellular senescence, a scratch test was applied to evaluate cell migration, and a transwell assay was used to analyze cell invasion. Western blotting and qRT-PCR methods were used to detect the protein and mRNA expression levels, respectively, of the FN1 gene and the related genes in the PI3K/AKT pathway (PI3K, AKT and PTEN), the cell cycle (pRb, CDK4 and Cyclin D1) and cell senescence (p16 and p21) among the collected tissues and cells. RESULTS: GSE12657 profiling revealed FN1 to be the most upregulated gene in glioma. Regarding the GSE12657 and GSE15824 datasets, FN1 gene expression was higher in glioma tissues than in normal tissues. GO enrichment analysis and KEGG pathway enrichment analysis indicated that FN1 is involved in the synthesis of extracellular matrix (ECM) components and the PI3K/AKT signaling pathway. Verification was provided, indicating the role played by the FN1 gene in the regulation of the PI3K/AKT signaling pathway, as silencing the FN1 gene was found to inhibit cell proliferation, promote cell apoptosis and senescence, and reduce migration and invasion through the down-regulation of FN1 gene expression and disruption of the PI3K-AKT signaling pathway. CONCLUSION: The findings of this study provide evidence highlighting the prominent role played by FN1 in stimulating glioma growth, invasion, and survival through the activation of the PI3K/AKT signaling pathway.

SJP-L-5 inhibits HIV-1 polypurine tract primed plus-strand DNA elongation, indicating viral DNA synthesis initiation at multiple sites under drug pressure.

In a previous study the small molecule SJP-L-5 that inhibits HIV replication, has been shown to block uncoating of the viral capsid. Continued study showed that SJP-L-5 might hinder HIV capsid uncoating by blocking the completion of reverse transcription. However, to date, the mechanism has not been fully elucidated. Here, the effects of SJP-L-5 for reverse transcription were explored via quantitative PCR, DIG-labelled ELISA, fluorescent resonance energy transfer, and Southern blot assays. We also analyzed the resistance profile of this compound against reverse transcriptase. Our results show that SJP-L-5 preferentially inhibits PPT primed plus-strand DNA synthesis (EC50 = 13.4 ± 3.0 µM) over RNA primed minus-strand DNA synthesis (EC50 > 3,646 µM), resulting in formation of five segmented plus-strand DNA and loss of HIV DNA flap, suggesting failure of both nuclear import and integration. Moreover, resistance study evidenced that SJP-L-5 requires the amino acid residues Val108 and Tyr181 to exert an inhibitory effect. These results indicate SJP-L-5 as a new non-nucleoside reverse transcriptase inhibitor that inhibits HIV-1 polypurine tract primed plus-strand DNA synthesis, initiating HIV-1 down-stream plus-strand DNA synthesis at multiple sites under drug pressure.

The influence of Schisandrin B on a model of Alzheimer's disease using ß-amyloid protein Aß1-42-mediated damage in SH-SY5Y neuronal cell line and underlying mechanisms.

Schisandrin B, an active substance, is derived from Chinese herb fruit Wuweizi, which exerts various pharmacological activities and has displayed significant beneficial effects in ameliorating Alzheimer's disease (AD). The aim of this study was to further extend our examination for the use of schisandrin B extract in the potential treatment of AD effects by investigating DNA methylation (DNMT), known to be modified in this disease using SH-SY5Y neuronal cell line exposed to ß-amyloid protein (Aß1-42). In particular, the purpose of this investigation was to examine alterations in mRNA and protein expression of DNMT. Data demonstrated that schisandrin B blocked Aß1-42-mediated injury in SH-SY5Y neuronal cell line as evidenced by a restoration of cellular morphology and cell viability to approximate control levels at the highest 10 µg/ml Schisandrin B. Incubation with Aß1-42 significantly decreased mRNA and protein expression of DNMT3A and DNMT1 in SH-SY5Y neuronal cell line. Incubation with Aß1-42 followed by 24 treatment with schisandrin B significantly inhibited the Aß1-42 -induced changes in mRNA and protein expression of DNMT3A and DNMT3B in a concentration-dependent manner. It is of interest that the mRNA expression of DNMT3A and DNMT1 were significantly higher than control. Data thus indicate schisandrin B was effective in inhibiting the actions of Aß1-42 on cell survival and morphology and that DNA methylation may be associated with the beneficial findings.

Exendin-4 Ameliorates Lipotoxicity-induced Glomerular Endothelial Cell Injury by Improving ABC Transporter A1-mediated Cholesterol Efflux in Diabetic apoE Knockout Mice.

ATP-binding cassette transporter A1 (ABCA1), which promotes cholesterol efflux from cells and inhibits inflammatory responses, is highly expressed in the kidney. Research has shown that exendin-4, a glucagon-like peptide-1 receptor (GLP-1R) agonist, promotes ABCA1 expression in multiple tissues and organs; however, the mechanisms underlying exendin-4 induction of ABCA1 expression in glomerular endothelial cells are not fully understood. In this study we investigated the effect of exendin-4 on ABCA1 in glomerular endothelial cells of diabetic kidney disease (DKD) and the possible mechanism. We observed a marked increase in glomerular lipid deposits in tissues of patients with DKD and diabetic apolipoprotein E knock-out (apoE-/-) mice by Oil Red O staining and biochemical analysis of cholesterol. We found significantly decreased ABCA1 expression in glomerular endothelial cells of diabetic apoE-/- mice and increased renal lipid, cholesterol, and inflammatory cytokine levels. Exendin-4 decreased renal cholesterol accumulation and inflammation and increased cholesterol efflux by up-regulating ABCA1. In human glomerular endothelial cells, GLP-1R-mediated signaling pathways (e.g. Ca2+/calmodulin-dependent protein kinase, cAMP/PKA, PI3K/AKT, and ERK1/2) were involved in cholesterol efflux and inflammatory responses by regulating ABCA1 expression. We propose that exendin-4 increases ABCA1 expression in glomerular endothelial cells, which plays an important role in alleviating renal lipid accumulation, inflammation, and proteinuria in mice with type 2 diabetes.

SJP-L-5, a novel small-molecule compound, inhibits HIV-1 infection by blocking viral DNA nuclear entry.

BACKGROUND: Small-molecule compounds that inhibit human immunodeficiency virus type 1 (HIV-1) infection can be used not only as drug candidates, but also as reagents to dissect the life cycle of the virus. Thus, it is desirable to have an arsenal of such compounds that inhibit HIV-1 infection by various mechanisms. Until now, only a few small-molecule compounds that inhibit nuclear entry of viral DNA have been documented. RESULTS: We identified a novel, small-molecule compound, SJP-L-5, that inhibits HIV-1 infection. SJP-L-5 is a nitrogen-containing, biphenyl compound whose synthesis was based on the dibenzocyclooctadiene lignan gomisin M2, an anti-HIV bioactive compound isolated from Schisandra micrantha A. C. Smith. SJP-L-5 displayed relatively low cytotoxicity (50% cytoxicity concentrations were greater than 200 µg/ml) and high antiviral activity against a variety of HIV strains (50% effective concentrations (EC50)) of HIV-1 laboratory-adapted strains ranged from 0.16-0.97 µg/ml; EC50s of primary isolates ranged from 1.96-5.33 µg/ml). Analyses of the viral DNA synthesis indicated that SJP-L-5 specifically blocks the entry of the HIV-1 pre-integration complex (PIC) into the nucleus. Further results implicated that SJP-L-5 inhibits the disassembly of HIV-1 particulate capsid in the cytoplasm of the infected cells. CONCLUSIONS: SJP-L-5 is a novel small-molecule compound that inhibits HIV-1 nuclear entry by blocking the disassembly of the viral core.

Maternal diabetes causes abnormal dynamic changes of endoplasmic reticulum during mouse oocyte maturation and early embryo development.

BACKGROUND: The adverse effects of maternal diabetes on oocyte maturation and embryo development have been reported. METHODS: In this study, we used time-lapse live cell imaging confocal microscopy to investigate the dynamic changes of ER and the effects of diabetes on the ER's structural dynamics during oocyte maturation, fertilization and early embryo development. RESULTS: We report that the ER first became remodeled into a dense ring around the developing MI spindle, and then surrounded the spindle during migration to the cortex. ER reorganization during mouse early embryo development was characterized by striking localization around the pronuclei in the equatorial section, in addition to larger areas of fluorescence deeper within the cytoplasm. In contrast, in diabetic mice, the ER displayed a significantly higher percentage of homogeneous distribution patterns throughout the entire ooplasm during oocyte maturation and early embryo development. In addition, a higher frequency of large ER aggregations was detected in GV oocytes and two cell embryos from diabetic mice. CONCLUSIONS: These results suggest that the diabetic condition adversely affects the ER distribution pattern during mouse oocyte maturation and early embryo development.

[Changes of neuroglobin in the pathologic process of contusion and laceration of brain in children].

OBJECTIVE: To study the role of neuroglobin (Ngb) in the pathologic process of contusion and laceration of brain in children. METHODS: The proteins in the brain tissue were extracted by two-dimensional gel electrophoresis in 3 children undergoing brain ventricular neoplasms resection (normal brain tissue) and in 8 children with contusion and laceration of brain. The image analysis was done using the PDQuest 7.0 software. The differential protein spots were detected and analyzed with Applied Biosystems Voyager System 4307 MALDI-TOF Mass Spectrometer and bioinformatical skills. Ngb expression in the brain tissue was measured using immunohistochemisty. Ngb expression in plasma was measured using ELISA in 15 children with contusion and laceration of brain and 10 healthy children. RESULTS: Expression maps of the brain tissue were established by two-dimensional gel electrophoresis in children with contusion and laceration of brain and healthy children. Six differential protein spots were found and 5 of them were identified by mass spectrum. Immunohistochemisty assay showed that Ngb expression in the brain tissue in children with contusion and laceration of brain was significantly higher than in normal controls (P<0.05). ELISA results showed that Ngb expression in the plasma increased significantly 6, 12, 18, 24 and 48 hours after trauma in children with contusion and laceration of brain compared with healthy children (P<0.01). CONCLUSIONS: Ngb may play an important role in the pathologic process of contusion and laceration of brain in children.