Isocucurbitacin B inhibits glioma growth through PI3K/AKT pathways and increases glioma sensitivity to TMZ by inhibiting hsa-mir-1286a.

Aim: Glioma accounts for 81% of all cancers of the nervous system cancers and presents one of the most drug-resistant malignancies, resulting in a relatively high mortality rate. Despite extensive efforts, the complete treatment options for glioma remain elusive. The effect of isocucurbitacin B (isocuB), a natural compound extracted from melon pedicels, on glioma has not been investigated. This study aims to investigate the inhibitory effect of isocuB on glioma and elucidate its underlying mechanisms, with the objective of developing it as a potential therapeutic agent for glioma. Methods: We used network pharmacology and bioinformatics analysis to predict potential targets and associated pathways of isocuB in glioma. Subsequently, the inhibitory effect of isocuB on glioma and its related mechanisms were assessed through Counting Kit-8 (CCK-8), wound healing, transwell, Western blot (WB), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and other in vitro experiments, alongside tumor formation experiments in nude mice. Results: Based on this investigation, it suggested that isocuB might inhibit the growth of gliomas through the PI3K-AKT and MAPK pathways. Additionally, we proposed that isocuB may enhance glioma drug sensitivity to temozolomide (TMZ) via modulation of hsa-mir-1286a. The CCK-8 assay revealed that isocuB exhibited inhibitory effects on U251 and U87 proliferation and outperformed TMZ. Wound healing and transwell experiments showed that isocuB inhibited the invasion and migration of U251 cells by suppressing the activity of MMP-2/9, N-cadherin, and Vimentin. The TdT-mediated dUTP-biotin nick end labeling (TUNEL) and flow cytometry (FCM) assays revealed that isocuB induced cell apoptosis through inhibition of BCL-2. Subsequently, we conducted RT-qPCR and WB experiments, which revealed that PI3K/AKT and MAPK pathways might be involved in the mechanism of the inhibition isocuB on glioma. Additionally, isocuB promoted the sensitivity of glioma U251 to TMZ by inhibiting hsa-mir-1286a. Furthermore, we constructed TMZ-resistant U251 strains and demonstrated effective inhibition by isocuB against these resistant strains. Finally, we confirmed that isocuB can inhibit tumor growth in vivo through experiments on tumors in nude mice. Conclusion: IsocuB may protect against glioma by acting on the PI3K/AKT and MAPK pathways and promote the sensitivity of glioma U251 to TMZ by inhibiting hsa-mir-1286a.

Intracardiac echocardiography-guided catheter ablation of highly symptomatic accelerated idioventricular rhythm originating from the right ventricular apical diverticulum.

Ventricular diverticula are saccule-like structures formed by the protrusion of the ventricular myocardium from the endocardial surface towards the free wall. Most diverticula are muscular structures, and patients usually have no obvious clinical symptoms. However, diverticula may contribute to arrhythmogenesis due to localized myocardial structural disturbances. Right ventricular apical diverticulum (RVAD) is very rare, and we report a case of highly symptomatic accelerated idioventricular rhythm (AIVR) originating from the RVAD that underwent intracardiac echocardiography (ICE)-guided catheter ablation with no recurrence during follow-up.

[Trueness of different digital design methods for incisal guidance of maxillary anterior implant-supported single crowns].

OBJECTIVE: To compare the trueness of incisal guidance of implant-supported single crowns designed by patient-specific motion (PSM) with that designed by average-value virtual articulator (AVA). METHODS: The study had recruited 12 participants with complete dentition and stable incisal guidance. An intraoral scanner was used to scan digital casts and record two types of patient-specific motion (data only including protrusive movement, and data including protrusive movement and lateral protrusive movement). The lingual surfaces of the maxillary incisors which guided the protrusive movement was selected and elevated to create a reference cast. A maxillary central incisor of original casts was vir-tually extracted and implanted to generate a working cast. The Dental system software program was used to design implant-supported single crowns with the anatomical coping design method. The incisal guidance was designed by different methods. The incisal guidance in control group was designed by the average-value virtual articulator. The incisal guidance in experiment groups was designed by the patient-specific motion only including protrusive movement (PSM1) and with the patient-specific motion including protrusive movement and lateral protrusive movement (PSM2). The incisal guidance of prosthesis designed by these 3 methods were compared with the original incisal guidance in Geomagic Control 2015 (3DSystem, America). The measurements included: Average of positive values, ratio of positive area and maximum value reflecting supra-occlusion; average of negative values, ratio of negative area and minimum value reflecting over-correction; and root mean square reflecting overall deviation. RESULTS: Statistical data were collected using the median (interquartile range) method. The average of positive values, ratio of positive area and average of negative values of the PSM2 group were smaller than those of the control group [8.0 (18.8) µm vs. 37.5 (47.5) µm; 0 vs. 7.2% (38.1%); -109.0 (63.8) µm vs.-66.5 (64.5) µm], and the ratio of negative area of PSM2 group was larger than those of the control group [52.9% (47.8%) vs. 17.3% (45.3%)], with significant differences (P all < 0.05). The ratio of positive area [0.1% (7.0%)] and average of negative values [-97.0 (61.5) µm] of PSM1 group, were smaller than those of the control group, and the ratio of negative area [40.7% (39.2%)] of the PSM1 group was larger than that of the control group, with significant differences (P < 0.05). The average of positive values [20.0 (42.0) µm] and ratio of positive area of PSM1 group was larger than that of the PSM2 group with significant differences (P < 0.05). CONCLUSION: To establish the incisor guidance of implant-supported single crowns, compared with the average-value virtual articulator and the patient-specific motion only including protrusive movement, the patient-specific motion including protrusive movement and lateral protrusive movement is more conducive to reducing the protrusive interference of prosthesis and improving the occlusal fit.

Regulated cell death in glioma: promising targets for natural small-molecule compounds.

Gliomas are prevalent malignant tumors in adults, which can be categorized as either localized or diffuse gliomas. Glioblastoma is the most aggressive and deadliest form of glioma. Currently, there is no complete cure, and the median survival time is less than one year. The main mechanism of regulated cell death involves organisms coordinating the elimination of damaged cells at risk of tumor transformation or cells hijacked by microorganisms for pathogen replication. This process includes apoptosis, necroptosis, autophagy, ferroptosis, pyroptosis, necrosis, parthanayosis, entosis, lysosome-dependent death, NETosis, oxiptosis, alkaliptosis, and disulfidaptosis. The main goal of clinical oncology is to develop therapies that promote the effective elimination of cancer cells by regulating cell death are the main goal of clinical oncology. Recently, scientists have utilized pertinent regulatory factors and natural small-molecule compounds to induce regulated cell death for the treatment of gliomas. By analyzing the PubMed and Web of Science databases, this paper reviews the research progress on the regulation of cell death and the role of natural small-molecule compounds in glioma. The aim is to provide help for the treatment of glioblastoma.

Research progress of delivery strategies related mucus barrier in mucosal drug delivery / 药学学报

The mucous barrier is a major physiological obstacle that the mucosal drug delivery system needs to deal with. In response to this physiological barrier, many achievements have been made in research of mucosal adhesion and mucus penetration. This review puts emphasis on the progress of the research on new mucosal adhesion strategies such as cationization, sulfhydrylization, maleimide functionalization, lectinization and catechol conjugation; polyethylene glycol (PEG), polyvinyl alcohol (PVA), poly (2-alkyl-2-oxazoline) (POZ), zwitterionic polymers and other mucus-inert materials, strategies to enhance mucus penetration ability such as enzyme functionalization, reducing agent pretreatment and so on. The problems of each strategy are also analyzed and discussed, which can provide some references for clinical transformation.

Preparation of oxytocin liposomes modified by cell penetrating peptides and evaluation on brain targeting efficiency via intranasal delivery / 药学学报

The water-soluble polypeptide drug oxytocin was encapsulated in liposomes by reverse-phase evaporation vesicle method to obtain oxytocin loaded liposomes (OT@LPs) which was further modified with cationic cell penetrating peptide—arginine octamer (R8) to get R8 modified oxytocin loaded liposomes (OT@LPs-R8) which showed enhanced mucoadhesive. The brain targeting efficiency was evaluated preliminarily after nasal administration. OT@LPs-R8 showed a round shape with a particle size distribution of 110.2 ± 7.3 nm, a surface potential as high as +18 mV, a drug loading (62.17 ± 1.88) %, an encapsulation rate (5.85 ± 0.72) %, and stood stable in nasal mucus. After nasal administration, it could significantly prolong the retention and enhance the distribution in the brain with no irritation to the nasal mucosa. The animal experiment in line with the regulations of the Department of Laboratory Animal Science of Fudan University on the ethics of animal experiments had been carried out after passing the review of the Animal Ethics Committee of Fudan University. The results showed nasal administration of OT@LPs-R8 could promote oxytocin directly into the brain from the nose which expected to become a new carrier for delivery of oxytocin to the brain.

Response of growth and photosynthetic characteristics of Polygonatum cyrtonema to shading conditions / 中国中药杂志

The purpose of this experiment was to study the effects of different shading conditions on the growth,physiological characteristics and biomass allocation of Polygonatum cyrtonema,which offered a theoretical basis for its cultivation.Different light environments(100%,80%,60% and 35% light transmittance) were simulated with shading treatments.Growth and photosynthetic indexes of P.cyrtonema were measured and the variances were analyzed.The results show that shading decreased superoxide anion radical(O-·2)production rate and hydrogen peroxide(H_2O_2) accumulation,kept the activity of SOD,POD and CAT enzyme at a high level.Furthermore,The content of chlorophyll a and chlorophyll b,net photosynthetic rate(Pn),stomatal conductance(Gs),transpiration rate(Tr),maximal photochemical efficiency of photosystem Ⅱ(Fv/Fm),photochemical quenching index(q P) and effective quantum yield of photosystem II(ΦPSⅡ) of P.cyrtonema were increased while the intercellular CO2 concentration(Ci),Foand NPQ were decreased by shading.Shading is beneficial to P.cyrtonema growth,can increase the total biomass P.cyrtonema.The allocation proportion of biomass on the aerial portion of P.cyrtonema increased but underground parts decreased with increasing shading conditions.In this study,P.cyrtonema can grow well in shading conditions,shading is beneficial to the formation of the yield and quality of the rhizomes of P.cyrtonema,especially in 65% light transmittance.

The role of calcitonin gene-related peptide in migraine prevention by botulinum toxin type A

@#Objectives: Calcitonin gene-related peptide (CGRP) is currently considered to be a major contributing factor in migraine headache. Botulinum toxin type A (BTXA) was found to be effective in migraine prevention. However, the mechanism of action in patients was unknown. Using injection as in clinical setting, the study aimed to determine whether BTXA could decrease the sensitization of the trigeminovascular nociceptive system through the reduction of CGRP action. Methods: Adult male Wistar rats were pretreated with normal saline solution or BTXA before KCl application to induce cortical spreading depression (CSD) or NaCl application as a control. Regional cerebral blood flow at parietal cortex was measured for 90 min after KCl or NaCl application. Tissues from trigeminal ganglion (TG) and trigeminal nucleus caudalis (TNC) were then collected for CGRP and c-Fos measurement respectively. Results: BTXA pretreatment significantly decreased the cumulative blood flow and number of hyperemic peaks induced by KCl. Numbers of CGRP positive cells at TG and c-Fos positive cells at TNC were also reduced by BTXA.Conclusion: BTXA pretreatment reduced CGRP production and release from the TG leading to lessen CSD production and persistent activation of TNC which played a major role in migraine headache.

Effects of N and Zn interaction on growth, yield and active components of Agastache rugosa / 中国中药杂志

The study is aimed to explore the effect of combination use of nitrogen(N) and zinc(Zn) fertilizers on the growth, yield and the effective components of Agastache rugosa. A. rugosa was grown under two N application rate (120, 300 kg·hm⁻²) and five Zn levels (0, 20, 50, 100，150 kg·hm⁻²) under field condition. The effect of the treatments on the physiological indicators, distribution of nitrogen and zinc and volatile oil components of A. rugosa were studied. The results showed that the combination use of N and Zn could significantly affect the growth and development, yield and volatile oil components of A. rugosa. Under the test conditions, the highest yield of Agastaches Herba was obtained when 50 kg·hm⁻² of Zn fertilizer was applied with high N application rate of 300 kg·hm⁻². Under the same N application rate, the increase of Zn production was positively correlated with the amount of Zn application in a certain concentration range, but excessive Zn application led to the decrease of yield. With the increase of N application level, the content of Zn also significantly increased. The combination use of N and Zn increased the yield of Agastaches Herba. High level of N application was beneficial to the absorption and accumulation of N and Zn of A. rugosa. Zn fertilizer could also promote the absorption and accumulation of N of A. rugosa. The interaction between N and Zn had significant influence on the main chemical constituents of the volatile oil of A. rugosa. Among the volatile oil chemical constituents of A. rugosa the content of pulegone (34.56%-53.91%) and piperonyl methyl ether (18.86%-42.27%) were much higher. Under the same N application rate, different Zn application rates also had significant effects on the main chemical components of volatile oil.

Research progress and application of head finite element model / 医用生物力学

The finite element method (FEM) is a technology for numerical analysis which based on the development of the electronic computer,and also a more advanced biomechanical research method.Early FEM was applied in the fields of engineering science and technology.In recent years,FEM has been widely used for brain research in biomedical engineering.With the rapid development of traffic and transportation,the high incident of craniocerebral injury has become a serious threat to human health year by year.The biomechanical mechanism of craniocerebral injury can be well researched by establishing the finite element model of human head.In this review,establishment,development and application of human head finite element model are summarized,and the future research direction is discussed as well.

Research progress and application of head finite element model / 医用生物力学

The finite element method (FEM) is a technology for numerical analysis which based on the development of the electronic computer, and also a more advanced biomechanical research method. Early FEM was applied in the fields of engineering science and technology. In recent years, FEM has been widely used for brain research in biomedical engineering. With the rapid development of traffic and transportation, the high incident of craniocerebral injury has become a serious threat to human health year by year. The biomechanical mechanism of craniocerebral injury can be well researched by establishing the finite element model of human head. In this review, establishment, development and application of human head finite element model are summarized, and the future research direction is discussed as well.

Effect of IL-29 on trypsin-induced protease-activated receptor expression on P815 mast cells / 中国免疫学杂志

Objective:To investigate the modulatory effect of IL-29 on trypsin-induced protease activated receptors (PARs) ex-pression on P815 mast cell.Methods:After P815 mast cells were challenged with different concentrations of IL-29 alone or combined with trypsin for 2 h, 6 h and 16 h, the challenged cells were collected and analysed by flow cytometry to detect the protein expression of PARs on P815 cells, and analysed by real time RT-PCR to detect the mRNA expression of PARs on P 815 cells.Results:Compared with the corresponding control , IL-29 induced significantly decreased expression of PAR-1 at protein and mRNA level on P815 cells, and upregulated PAR-3, PAR-4 mRNA level on P815 cells, whereas IL-29 did little effect on the expressions of PAR-2,3,4 at protein level on P815 cells accordingly.Preincubation of mast cell with IL-29 did not alter trypsin-induced PAR-1 expression on P815 cells, whereas up-regulated expression of PAR-2, 3, 4 were detected when P815 cell were pre-treated with IL-29 before being challenged with trypsin compared with the corresponding control .Conclusion: IL-29 can upregulate trypsin-induced PARs expression on mast cells through which participated in mast cell related inflammation .

Protection of vanillin derivative VND3207 on plasmid DNA damage induced by different LET ionizing radiation / 中华放射医学与防护杂志

Objective To evaluate the radioprotective effect of vanillin derivative VND3207 on DNA damage induced by different LET ionizing radiation.Methods The plasmid DNA in liquid was irradiated by 60Co γ-rays, proton or 7Li heavy ion with or without VND3207.The conformation changes of plasmid DNA were assessed by agarose gel electrophoresis and the quantification was done using gel imaging system.Results The DNA damage induced by proton and 7Li heavy ion was much more serious as compared with that by 60Co γ-rays, and the vanillin derivative VND3207 could efficiently decrease the DNA damage induced by all three types of irradiation sources, which was expressed as a significantly reduced ratio of open circular form (OC) of plasmid DNA.The radioprotective effect of VND3207 increased with the increasing of drug concentration.The protective efficiencies of 200 μmol/L VND3207 were 85.3% (t =3.70,P =0.033), 73.3% (t = 10.58, P =0.017)and 80.4% (t =8.57,P =0.008)on DNA damage induction by 50 Gy of γ-rays, proton and 7Li heavy ion, respectively.It seemed that the radioprotection of VND3207 was more effective on DNA damage induced by high LET heavy ion than that by proton.Conclusions VND3207 has a protective effect against the genotoxicity of different LET ionizing radiation, especially for γ-rays and 7 Li heavy ion.

Characteristics of combining loss of heterozygosity of 1p/19q in glioma / 中华外科杂志

<p><b>OBJECTIVES</b>To find possible factors correlated with combined loss of heterozygosity (LOH) of 1p and 19q.</p><p><b>METHODS</b>The status of 1p and 19q of 138 glioma specimen from January 2009 to December 2009 was evaluated by Fluorescence in situ hybridization (FISH) method, and the frequencies of combining LOH of 1p/19q were compared between different pathologies, brain sub-regions, genders and ages.</p><p><b>RESULTS</b>The frequencies of combined LOH of 1p and 19q of oligodendroglial (81.3%) and oligo astrocytic tumors (55.8%) were significantly higher than that of astrocytic tumor (22.2%) (P < 0.01), and the frequency of oligodendroglial tumor was significantly higher than that of oligo astrocytic tumor (P < 0.05). The frequency of combining LOH of 1p and 19q in frontal lobe (61.8%) was higher than that in temporal (31.8%) and insular lobes (34.6%) (P < 0.05).</p><p><b>CONCLUSION</b>Combining LOH of 1p and 19q has significant correlation with the pathologies and brain sub-regions.</p>

siRNA-mediated silencing of Cockayne Cyndrome group B gene potentiates radiation-induced apoptosis and antiproliferative effect in HeLa cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Cockayne syndrome (CS) is a rare human genetic disorder characterized by increased UV sensitivity, developmental abnormalities and premature aging. Cells isolated from individuals with CS have a defect in transcription-coupled DNA repair. Despite the repair defect, there is no any increased risk of spontaneous or UV-induced cancer for CS individuals. The strategy of RNA interfering was used here to explore the potential radiosensitizing and anticancer activity of targeting CS group B (CSB) gene.</p><p><b>METHODS</b>The vectors encoding CSB-specific siRNAs were constructed by inserting duplex siRNA encoding oligonucleotides into the plasmid P(silencer TM 3.1). The cell lines expressing the CSB-siRNA were generated from HeLa cells transfected with the above vectors. Colony-forming ability was used to assay cell survival. Cell cycle was analyzed by FACScan flow cytometry. The apoptosis was measured by detecting the accumulation of sub-G(1) population as well as by fluorescence staining assay. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to semi-quantify mRNA expression. Protein level was detected by Western blotting analysis.</p><p><b>RESULTS</b>Two constructs encoding CSB-specific siRNA were generated, both of them resulted in remarkable suppression on CSB expression in HeLa cells, and led to an increased sensitivity to (gamma-ray and UV light. siRNA-mediated silencing of CSB decreased cell proliferation rate, increased spontaneous apoptosis as well as the occurrence of UV- or cisplatin-induced apoptosis by 2 to 3.5 fold. A significant S phase blockage and a remarkable reduction of G(1) population were induced in control HeLa cells at 18 hours after being exposed to 10 J/m(2) of UV light. The S phase blockage was also observed in UV-irradiated CSB-siRNA transfected HeLa cells, but the extent of increased S phase population was lower than that in the UV-irradiated control cells. No or a relative weak reduction on G(1) phase population was observed in UV-irradiated CSB-siRNA transfected HeLa cells. In addition, siRNA-mediated silencing of CSB promoted the elimination of G(2)/M phase cells after UV light radiation.</p><p><b>CONCLUSIONS</b>siRNA-mediated silencing of CSB causes cells to proliferate more slowly, sensitize cells to genotoxicants, and modify UV radiation-induced cell cycle changes. siRNA-mediated inactivation of CSB could be an attractive strategy for ameliorating cancer therapy, which can be fulfilled via the combination of gene therapy and sensitization of radiotherapy or chemotherapy.</p>

Sampling survey of disability in 0-6 year-old children in China / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To investigate the current status of disabled children and prevalence of disabilities in children aged 0-6 years and their risk factors, and to provide scientific evidence for making relevant policies for disabled children.</p><p><b>METHODS</b>In a community-based cross-sectional study, multi-phase, stratified, unequal proportional and cluster sampling was adopted to survey 60 124 children aged 0-6 years. All the investigated children were screened for disabilities, and those with positive screening tests were further diagnosed by various specialties.</p><p><b>RESULTS</b>A total of 819 children were diagnosed as disabled with an overall prevalence of 1.362%, 0.155% for hearing disability, 0.160% for visual disability, 0.931% for intelligent disability, 0.424% for limb disability, and 0.101% for mental disability. Prevalence of disability in children was higher in rural areas, and in families with two or more children, low educational level or in divorced families.</p><p><b>CONCLUSION</b>The prevalence of disability can be reduced by economic development, improvement of health care and quality of population, as well as harmonious familial relationship, early prevention of disability, and preschool education for disabled children.</p>