Association between epileptiform discharges and the sleep cycle in 200 epileptic patients.

OBJECTIVE: The poor sleep quality of epileptic patients may be partly due to the occurrence epileptiform discharges (EDs). We observed the number of interictal discharges in each sleep stage and explored the associations between EDs and sleep phases in epileptic patients. METHODS: Two hundred epileptic patients and 182 healthy volunteers were enrolled in the current study. For all subjects, video electroencephalography (EEG) monitoring and 24-hr night polysomnography were conducted to detect EDs and analyze the sleep structures. RESULTS: EDs were detected in 91% of epileptic patients with the most frequent cases from the temporal lobe. The EDs detected during waking, sleeping, or both waking and nonrapid eye movement (NREM) sleep stages 1-2 accounted for 7.1%, 19.2%, and 25.3% of the total patients, respectively. EDs were rare during NREM stages 3-4 with 1.1% of total patients mainly in the central-temporal lobe. The total sleep time and time spent in REM were similar between the epileptic patients and healthy volunteers. However, epileptic patients spent a significantly longer mean sleep time in NREM stages 1-2 (293.91 ± 27.57 min vs. 223.17 ±15.28; p = .000) and less in NREM stages 3-4 (50.11 ± 12.12 min vs. 133.96 ± 10.77; p = .000) than healthy volunteers. Furthermore, asymmetric sleep spindles and fragmentary sleep structure as well as high inversion frequency were found in 26.7% and 43.3% of epileptic patients, respectively. CONCLUSION: Combination of long-term video EEG with polysomnography is a useful method to analyze associations between EDs and the sleep-wake cycle. This strategy can also help identify the nature of sleep disorders in epileptic patients, which may improve the treatment efficacy.

Exploring the mechanism of action of licorice in the treatment of COVID-19 through bioinformatics analysis and molecular dynamics simulation.

Purpose: The rapid worldwide spread of Corona Virus Disease 2019 (COVID-19) has become not only a global challenge, but also a lack of effective clinical treatments. Studies have shown that licorice can significantly improve clinical symptoms such as fever, dry cough and shortness of breath in COVID-19 patients with no significant adverse effects. However, there is still a lack of in-depth analysis of the specific active ingredients of licorice in the treatment of COVID-19 and its mechanism of action. Therefore, we used molecular docking and molecular dynamics to explore the mechanism of action of licorice in the treatment of COVID-19. Methods: We used bioinformatics to screen active pharmaceutical ingredients and potential targets, the disease-core gene target-drug network was established and molecular docking was used for verification. Molecular dynamics simulations were carried out to verify that active ingredients were stably combined with protein targets. The supercomputer platform was used to measure and analyze stability of protein targets at the residue level, solvent accessible surface area, number of hydrogen bonds, radius of gyration and binding free energy. Results: Licorice had 255 gene targets, COVID-19 had 4,628 gene targets, the intersection gene targets were 101. Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene ontology (GO) analysis showed that licorice played an important role mainly through the signaling pathways of inflammatory factors and oxidative stress. Molecular docking showed that Glycyrol, Phaseol and Glyasperin F in licorice may playe a role in treating COVID-19 by acting on STAT3, IL2RA, MMP1, and CXCL8. Molecular dynamics were used to demonstrate and analyze the binding stability of active ingredients to protein targets. Conclusion: This study found that Phaseol in licorice may reduce inflammatory cell activation and inflammatory response by inhibiting the activation of CXCL8 and IL2RA; Glycyrol may regulate cell proliferation and survival by acting on STAT3. Glyasperin F may regulate cell growth by inhibiting the activation of MMP1, thus reducing tissue damage and cell death caused by excessive inflammatory response and promoting the growth of new tissues. Therefore, licorice is proposed as an effective candidate for the treatment of COVID-19 through STAT3, IL2RA, MMP1, and CXCL8.

The association of SULT1A1 codon 213 polymorphism and breast cancer susceptibility: meta-analysis from 16 studies involving 23,445 subjects.

Epidemiological studies on the association between SULT1A1 codon 213 polymorphism and breast cancer risk are inconclusive. In order to derive a more precise estimation of the association, a meta-analysis was conducted in this article. Sixteen studies including 9,881 cases and 13,564 controls were collected for SULT1A1 codon 213 polymorphism by searching the databases of Medline, PubMed, Embase, and ISI Web of Knowledge. The strength of association between SULT1A1 codon 213 polymorphism and breast cancer susceptibility was assessed by calculating crude ORs with 95% CIs. When all the 21 studies were pooled into the meta-analysis, there was no evidence for significant association between SULT1A1 codon 213 polymorphism and breast cancer susceptibility (for Arg/Arg versus Arg/His: OR = 0.999, 95% CI = 0.941-1.061; for Arg/Arg versus His/His: OR = 1.121, 95% CI = 1.013-1.242; for dominant model: OR = 1.128, 95% CI = 1.01-1.26; for recessive model: OR = 1.151, 95% CI = 0.950-1.394). In the subgroup analysis by the source of controls, significant increased risk was found for hospital-based studies (for Arg/Arg versus Arg/His: OR = 1.173, 95% CI = 1.000-1.376; for Arg/Arg versus His/His: OR = 1.600, 95% CI = 1.134-2.256; for dominant model: OR = 1.269, 95% CI = 1.134-2.256; for recessive model: OR = 1.664, 95% CI = 1.070-2.588). In summary, the meta-analysis suggests that SULT1A1 codon 213 polymorphism may be associated with the hospital-based studies. However, large number of samples and representative hospital-based studies with homogeneous breast cancer patients and well-matched controls are warranted to confirm this finding.

Experimental investigation of the immunoregulatory and anti-inflammatory effects of the traditional Chinese medicine "Li-Yan Zhi-Ke Granule" for relieving chronic pharyngitis in rats.

Chronic pharyngitis, a chronic inflammation of the pharyngeal mucous membrane and submucous lymphoid tissues, is often caused by unsatisfactory treatment of acute pharyngitis or repeated occurrences of upper respiratory tract infection and is related to a high-dust environment. Traditional herbal pharmacotherapy is well known for combining plant species to create complex phytochemical mixtures in the attempt to ameliorate pathophysiological processes. The aim of current study is to investigate the effect of immunoregulation and anti-inflammation with the traditional Chinese medicine (TCM) "Li-Yan Zhi-Ke Granule" in rats. Determination of serum hemolysin and the carbon particle clearance test were performed. The results demonstrate that administration of the TCM "Li-Yan Zhi-Ke Granule" may improve the effect of phagocytosis by mononuclear macrophages and immune function in rats, and may also increase the immunoregulatory and anti-inflammatory responses of rats with chronic pharyngitis. This traditional drug could relieve the symptoms of sore throat and cough in rats with chronic pharyngitis.

Synthesis and characterization of graft copolymer of chitosan and polyethylene glycol.

MPEG was modified with 1,1'-carbonyldiimidazole, then the activated MPEG reacted with primary amino groups of chitosan. Synthesize the graft copolymer of chitosan and polyethylene glycol in two steps. The structure of the copolymer was characterized by FT-IR and 1H-NMR. It agrees with the PEG content of classical stealth nanoparticles materials. The X-ray diffraction and DSC analysis proved that the crystallinity of the copolymer increased. It is a promising material for the stealth nanoparticles. It is a potential new carrier for the drug delivery systems of long-circulation and solid carcinoma.

Differential proteomics identification of HSP90 as potential serum biomarker in hepatocellular carcinoma by two-dimensional electrophoresis and mass spectrometry.

The aim of the current study is to identify the potential biomarkers involved in Hepatocellular carcinoma (HCC) carcinogenesis. A comparative proteomics approach was utilized to identify the differentially expressed proteins in the serum of 10 HCC patients and 10 controls. A total of 12 significantly altered proteins were identified by mass spectrometry. Of the 12 proteins identified, HSP90 was one of the most significantly altered proteins and its over-expression in the serum of 20 HCC patients was confirmed using ELISA analysis. The observations suggest that HSP90 might be a potential biomarker for early diagnosis, prognosis, and monitoring in the therapy of HCC. This work demonstrates that a comprehensive strategy of proteomic identification combined with further validation should be adopted in the field of cancer biomarker discovery.

Hybrid manganese dioxide-bovine serum albumin nanostructure incorporated with doxorubicin and IR780 for enhanced breast cancer chemo-photothermal therapy.

The therapeutic outcome of chemotherapy is limited, although it is still the preferent strategy for cancer therapy. By regulation of tumor microenvironment and introduction of another therapeutic manner for combination therapy can enhance the anticancer activity of chemotherapeutics. Herein, we have constructed a hybrid nanostructure which composed of manganese dioxide (MnO2) and doxorubicin (DOX) as well as IR780 by stabilizing with BSA (BMDI) in one-pot procedure to alleviate tumor hypoxia and enhance tumor growth inhibition. The MnO2 can react with H2O2 to generate oxygen, and additionally react with GSH to realize tumor microenvironment responsive drug controlled release. And the release Mn ions further enhanced the magnetic resonance signal which made the BMDI a promising contrast agent for MRI. Moreover, the introduction of MnO2 has enhanced the anticancer activity of DOX in vitro and in vivo, and efficiently suppressed the tumor growth. By further introducing with photothermal therapy (PTT), the tumor growth was almost inhibited. It demonstrated that the BMDI hybrid nanostructure has great potential in tumor growth inhibition as therapeutics carrier.

[Effects of 5-HT1A receptor antagonist on ethanol induced hypothermia and behavioral thermoregulatory response in rats].

OBJECTIVE: To observe the effects of 5-HT1Areceptor antagonist p-MPI on ethanol induced hypothermia and behavioral ther-moregulatory response in rats. METHODS: Core temperature and motor activities were monitored in undisturbed male SD rats using radioteleme-try. The behavioral thermoregulatory response and core temperature were monitored in rats using radiotelemetric temperature gradient apparatus. The rats were placed in a temperature gradient that permitted the selection of ambient temperature ranging from 15℃ to 40℃. Effect of ethanol (3 g/kg) and 5-HT1A receptor antagonist p-MPPI(1 mg/kg) on core temperature, motor activities, and the behavioral thermoregulatory re-sponse were observed in rats. RESULTS: ①Ethanol led to a rapid reduction in core temperature. The hypothermic responses were accompanied with a preference for cooler ambient temperature. ②5-HT1A receptor antagonist attenuated the hypothermia induced by ethanol, and accompa-nied with a selection for warmer ambient temperature. CONCLUSIONS: ①Behavioral thermoregulatory observations suggested that the ethanol could decrease the thermoregulatory set point,because rats treated with ethanol selected cooler ambient temperature facilitates the reduction in core temperature.②5-HT might be involved in ethanol-induced hypothermia and behavioral thermoregulatory response.

Casitas B-Lineage Lymphoma RING Domain Inhibitors Protect Mice against High-Fat Diet-Induced Obesity and Insulin Resistance.

The casitas b-lineage lymphoma (c-Cbl) is an important adaptor protein with an intrinsic E3 ubiquitin ligase activity that interacts with E2 proteins such as UbCH7. c-Cbl plays a vital role in regulating receptor tyrosine kinase signaling. c-Cbl involves in whole-body energy homeostasis, which makes it a potential target for the treatment of type 2 diabetes and obesity. In the present study, we have designed two parental peptides and 55 modified peptides based on the structure of UbCH7 loop L1 and L2. Thirteen of the modified peptides showed increased inhibitory activity in a fluorescence polarization-based assay. In the in vivo proof of study principle, mice treated with peptides 10, 34, 49 and 51 were protected against high-fat diet-induced obesity and insulin resistant. These inhibitors may potentially lead to new therapeutic alternatives for obesity and type 2 diabetes.

A case of schizencephaly has a normal surface EEG but abnormal intracranial EEG: epilepsia partialis continua or dystonia?

Schizencephaly is a congenital malformation of the cerebral hemispheres, with communication between the lateral ventricle and the subarachnoid space. Marinelli reported that schizencephaly may be associated with continuous involuntary hand movements, such as dystonia or epilepsia partialis continua (EPC). We describe a young Chinese patient with continuous involuntary movements of the contralateral hand affected by schizencephaly. He has a normal scalp electroencephalogram (EEG) but abnormal intracranial EEG, with synchronized periodic lateralized epileptiform discharges. The results obtained from these EEG investigations and the clinical features of the involuntary movements are in favor of a diagnosis of secondary EPC.

Identification of adiponectin receptor agonist utilizing a fluorescence polarization based high throughput assay.

Adiponectin, the adipose-derived hormone, plays an important role in the suppression of metabolic disorders that can result in type 2 diabetes, obesity, and atherosclerosis. It has been shown that up-regulation of adiponectin or adiponectin receptor has a number of therapeutic benefits. Given that it is hard to convert the full size adiponectin protein into a viable drug, adiponectin receptor agonists could be designed or identified using high-throughput screening. Here, we report on the development of a two-step screening process to identify adiponectin agonists. First step, we developed a high throughput screening assay based on fluorescence polarization to identify adiponectin ligands. The fluorescence polarization assay reported here could be adapted to screening against larger small molecular compound libraries. A natural product library containing 10,000 compounds was screened and 9 hits were selected for validation. These compounds have been taken for the second-step in vitro tests to confirm their agonistic activity. The most active adiponectin receptor 1 agonists are matairesinol, arctiin, (-)-arctigenin and gramine. The most active adiponectin receptor 2 agonists are parthenolide, taxifoliol, deoxyschizandrin, and syringin. These compounds may be useful drug candidates for hypoadiponectin related diseases.

Development of a fluorescence polarization based high-throughput assay to identify Casitas B-lineage lymphoma RING domain regulators.

The E3 ubiquitin protein ligase Casitas B-lineage Lymphoma (Cbl) proteins and their binding partners play an important role in regulating signal transduction pathways. It is important to utilize regulators to study the protein-protein interactions (PPIs) between these proteins. However, finding specific small-molecule regulators of PPIs remains a significant challenge due to the fact that the interfaces involved in PPIs are not well suited for effective small molecule binding. We report the development of a competitive, homogeneous, high-throughput fluorescence polarization (FP) assay to identify small molecule regulators of Cbl (RING) domain. The FP assay was used to measure binding affinities and inhibition constants of UbCH7 peptides and small molecule regulators of Cbl (RING) domains, respectively. In order to rule out promiscuous, aggregation-based inhibition, two assay conditions were developed and compared side by side. Under optimized conditions, we screened a 10,000 natural compound library in detergent-free and detergent-present (0.01% Triton X-100) systems. The results indicate that the detergent-present system is more suitable for high-throughput screens. Three potential compounds, methylprotodioscin, leonuride and catalpol, have been identified that bind to Cbl (RING) domain and interfere with the Cbl (RING)-UbCH7 protein-protein interaction.