Rapid and sustained resolution in generalized pustular psoriasis with IL-17A inhibitors required high adherence: a 96-week analysis in a real-life setting.

BACKGROUND: Generalized pustular psoriasis (GPP) is a rare, potentially life-threatening skin disease often requiring long-term therapy. We aimed to evaluate the use of Interleukin (IL)-17A inhibitors (secukinumab and ixekizumab) in GPP patients over 96 weeks. METHODS: We retrospectively analyzed a case series of 18 patients with GPP who received secukinumab (n = 13) and ixekizumab (n = 5) therapy with a 96-week follow-up period. The primary effectiveness analysis included determining the percentage of patients who achieved ≥90% or 100% improvement in the Generalized Pustular Psoriasis Area and Severity Index (GPPASI) score. Adherence was captured using the medication possession ratio (MPR). RESULTS: Using the as-observed (AO) method, 87% and 67% of patients treated with secukinumab or ixekizumab achieved GPPASI 90 and 100 responses, respectively. At Week 96, the mean GPPASI improvements from baseline GPPASI were 96.3% (95% CI: 0.91-1.01) using the AO method. After Week 48, 14 patients tapered (n = 8) or terminated (n = 6) the treatment. High-adherence therapy (MPR ≥ 80%) was significantly superior to the low-adherence group in the rate of patients achieving a GPPASI 100 response (AO, 100% vs. 38%, P < 0.05). By Week 96, 5 (27.8%) patients had new GPP flares, and 4 (80%) were in the low-adherence group. No new safety signals occurred. CONCLUSION: IL-17A inhibitors led to effective and sustained improvement in GPP patients, and high-adherence therapy had long-term positive effects on skin clearance. Given its relapsing nature, improving compliance is beneficial for long-term clinical management.

The role of neuroglial cells communication in ischemic stroke.

Ischemic stroke is one of the leading causes of death and disability globally, but its treatment options are limited due to therapeutic window and reperfusion injury constraints. Microglia, astrocytes, and oligodendrocytes are the major components of the neurovascular unit, and there is substantial evidence suggesting their contributions to maintaining homeostasis in the central nervous system. Neuroglial cells participate in neuronal physiological functions and the repair of damaged neurons through various communication methods, including gap junctions, chemical signaling, and extracellular vesicles, in conjunction with other components of the neurovascular unit. Ischemia-induced microglia and astrocytes polarize into "M1/M2" and "A1/A2" phenotypes and exert neurotoxic or neuroprotective effects by releasing soluble factors, secreting extracellular vesicles, and forming syncytia networks in the acute (<72 h), subacute (>72 h), and chronic phases (>6 weeks). Apoptosis of oligodendrocytes due to ischemic hypoxia leads to white matter injury, causing long-term cognitive dysfunction, and promoting oligodendrogenesis is a crucial direction for achieving functional recovery in ischemic stroke. In this article, we summarize the cellular interactions following cerebral ischemia, analyze the roles of neuroglial cells through gap junctions, chemical signaling, and extracellular vesicles in different stages of ischemic stroke, and further explore strategies for intervening in ischemic stroke.

Matrine suppresses liver cancer progression and the Warburg effect by regulating the circROBO1/miR-130a-5p/ROBO1 axis.

Matrine, an effective component extracted from the traditional Chinese herb, Sophora flavescens, has been indicated to exert antitumor activity in different types of cancer. However, the role and precise mechanism of matrine in the progression of liver cancer remains largely unclear. Cell viability, cell proliferation, cell apoptosis, and Warburg effect were estimated by cell counting kit-8 assay, colony formation assay, flow cytometry assay, and glucose uptake and lactate production assay, respectively. The candidate Circular RNAs (circRNAs) were screened by integrating the Gene Expression Omnibus database (GSE155949) analysis with the online program GEO2R. A quantitative real-time polymerase chain reaction was employed to test the expression of circRNA circROBO1, microRNA miR-130a-5p, and roundabout homolog 1 (ROBO1). The interaction of circROBO1/miR-130a-5p/ROBO1 axis was predicted and confirmed by bioinformatics analysis, a dual-luciferase reporter assay, and an RNA pull-down assay. A xenograft mouse model was employed to reveal the role of matrine in vivo. Matrine repressed liver cancer cell viability, proliferation, and Warburg effect, but increased cell apoptosis in vitro. CircROBO1 and ROBO1 were upregulated, but miR-130a-5p was downregulated in liver cancer tissues. Additionally, matrine could reduce the expression of circROBO1 and ROBO1, and increase the expression of miR-130a-5p. Mechanically, overexpression of circROBO1 partly recovered the effect of matrine on liver cancer cell viability, proliferation, apoptosis, and Warburg effect by regulating the miR-130a-5p/ROBO1 axis. Matrine impeded liver cancer development by mediating the circROBO1/miR-130a-5p/ROBO1 axis, which provided a theoretical basis for the application of matrine as an effective anticancer drug for liver cancer.

Exploring the Temporal Patterns of Dynamic Information Flow during Attention Network Test (ANT).

The attentional processes are conceptualized as a system of anatomical brain areas involving three specialized networks of alerting, orienting and executive control, each of which has been proven to have a relation with specified time-frequency oscillations through electrophysiological techniques. Nevertheless, at present, it is still unclear how the idea of these three independent attention networks is reflected in the specific short-time topology propagation of the brain, assembled with complexity and precision. In this study, we investigated the temporal patterns of dynamic information flow in each attention network via electroencephalograph (EEG)-based analysis. A modified version of the attention network test (ANT) with an EEG recording was adopted to probe the dynamic topology propagation in the three attention networks. First, the event-related potentials (ERP) analysis was used to extract sub-stage networks corresponding to the role of each attention network. Then, the dynamic network model of each attention network was constructed by post hoc test between conditions followed by the short-time-windows fitting model and brain network construction. We found that the alerting involved long-range interaction among the prefrontal cortex and posterior cortex of brain. The orienting elicited more sparse information flow after the target onset in the frequency band 1-30 Hz, and the executive control contained complex top-down control originating from the frontal cortex of the brain. Moreover, the switch of the activated regions in the associated time courses was elicited in attention networks contributing to diverse processing stages, which further extends our knowledge of the mechanism of attention networks.

Choroid plexus epithelium and its role in neurological diseases.

Choroid plexus epithelial cells can secrete cerebrospinal fluid into the ventricles, serving as the major structural basis of the selective barrier between the neurological system and blood in the brain. In fact, choroid plexus epithelial cells release the majority of cerebrospinal fluid, which is connected with particular ion channels in choroid plexus epithelial cells. Choroid plexus epithelial cells also produce and secrete a number of essential growth factors and peptides that help the injured cerebrovascular system heal. The pathophysiology of major neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, as well as minor brain damage diseases like hydrocephalus and stroke is still unknown. Few studies have previously connected choroid plexus epithelial cells to the etiology of these serious brain disorders. Therefore, in the hopes of discovering novel treatment options for linked conditions, this review extensively analyzes the association between choroid plexus epithelial cells and the etiology of neurological diseases such as Alzheimer's disease and hydrocephalus. Finally, we review CPE based immunotherapy, choroid plexus cauterization, choroid plexus transplantation, and gene therapy.

Polarized light compass-aided inertial navigation under discontinuous observations environment.

In recent years, integrated polarized light/inertial heading measurement systems have been widely used to obtain autonomous heading measurements of small unmanned combat platforms in the case of satellite navigation rejection. However, existing polarized light/inertial heading measurement systems have certain limitations. For example, they can only measure the heading angle in environments where continuous observations can be obtained. When encountering a complex environment with trees and/or tall buildings, the measured heading angle will contain sharp noise which greatly affects its accuracy. In particular, when encountering an underpass, it will lead to the complete loss of lock of the polarized light compass signal. Therefore, for the problem of sharp noise arising from a complex environment, a robust Cubature Kalman filter (CKF) data-fusion algorithm is proposed and verified by experiments. It is proved that the robust CKF algorithm has a certain ability to filter out the effects of poor measurements. After application of the robust CKF algorithm, the Root Mean Square Error (RMSE) of the heading angle reaches 0.3612°. This method solves the problem of low precision and poor stability of the polarized light/inertial system when high buildings and/or trees are contained in a complex environment. Next, in view of the problem that the polarized light compass signal is completely lost due to passing through an underground passage, a random forest regression (RFR) neural network model is established and introduced into the combined system. Simulated and outdoor experiments are carried out to verify the designed model using data obtained with a vehicle. The RMSE of the heading angle obtained in the experiment is 1.1894°, which solves the problem that the polarized light/inertial system cannot utilize discontinuous observations when attempting to detect the carrier heading angle.

Jasmonate-Responsive Transcription Factors NnWRKY70a and NnWRKY70b Positively Regulate Benzylisoquinoline Alkaloid Biosynthesis in Lotus (Nelumbo nucifera).

Lotus (Nelumbo nucifera) is a large aquatic plant that accumulates pharmacologically significant benzylisoquinoline alkaloids (BIAs). However, little is known about their biosynthesis and regulation. Here, we show that the two group III WRKY transcription factors (TFs), NnWRKY70a and NnWRKY70b, positively regulate the BIA biosynthesis in lotus. Both NnWRKY70s are jasmonic acid (JA) responsive, with their expression profiles highly correlated to the BIA concentration and BIA pathway gene expression. A dual-luciferase assay showed that NnWRKY70a could transactivate the NnTYDC promoter, whereas NnWRKY70b could activate promoters of the three BIA structural genes, including NnTYDC, NnCYP80G, and Nn7OMT. In addition, the transient overexpression of NnWRKY70a and NnWRKY70b in lotus petals significantly elevated the BIA alkaloid concentrations. Notably, NnWRKY70b seems to be a stronger BIA biosynthesis regulator, because it dramatically induced more BIA structural gene expressions and BIA accumulation than NnWRKY70a. A yeast two-hybrid assay further revealed that NnWRKY70b physically interacted with NnJAZ1 and two other group III WRKY TFs (NnWRKY53b and NnWRKY70a), suggesting that it may cooperate with the other group III WRKYs to adjust the lotus BIA biosynthesis via the JA-signaling pathway. To illustrate the mechanism underlying NnWRKY70b-mediated BIA regulation in the lotus, a simplified model is proposed. Our study provides useful insights into the regulatory roles of WRKY TFs in the biosynthesis of secondary metabolites.

Overexpression of OASL upregulates TET1 to induce aberrant activation of CD4+ T cells in systemic sclerosis via IRF1 signaling.

BACKGROUND: Systemic sclerosis (SSc), an autoimmune disease with unknown etiology and pathogenesis, is characterized by abnormal autoimmunity, vascular dysfunction, and progressive fibrosis of skin and organs. Studies have shown that a key factor in the pathogenesis of SSc is aberrant activation of CD4+ T cells. Our previous studies have shown that a global hypomethylation state of CD4+ T cells is closely related to aberrant activation. However, the exact mechanism of hypomethylation in CD4+T cells is not yet clear. METHODS: Illumina HiSeq 2500 Platform was used to screen differentially expressed genes and explore the role of OASL, TET1, and IRF1 in the abnormal activation of CD4+T cells in SSc. Finally, double luciferase reporter gene experiments were used to analyze the interaction between IRF1 and TET1. RESULTS: OASL overexpression could upregulate TET1 to increase the hydroxymethylation levels of CD4+ T cells and induce high expression of functional proteins (CD40L and CD70), thus promoting CD4+T cell aberrant activation. Moreover, OASL upregulated TET1 via IRF1 signaling activation, and a double luciferase reporter gene experiment revealed that IRF1 can bind to the TET1 promoter region to regulate its expression. CONCLUSIONS: OASL participates in the regulation of abnormal hypomethylation of CD4+ T cells in SSc, which implies a pivotal role for IFN signaling in the pathogenesis of SSc. Regulating DNA methylation and IFN signaling may serve as therapeutic treatments in SSc.

Genistein-3'-sodium sulfonate ameliorates cerebral ischemia injuries by blocking neuroinflammation through the α7nAChR-JAK2/STAT3 signaling pathway in rats.

BACKGROUND: Neuroinflammation plays a pivotal role in the acute progression of cerebral ischemia/reperfusion injury (I/RI). We previously reported that genistein-3'-sodium sulfonate (GSS), a derivative from the extract of the phytoestrogen genistein (Gen), protects cortical neurons against focal cerebral ischemia. However, the molecular mechanism underlying the neuroprotective effects exerted by GSS remains unclear. PURPOSE: The present study focused on the anti-inflammatory effects of GSS following I/RI in rats. STUDY DESIGN: Randomized controlled trial. METHODS: The tMCAO rat model and LPS-stimulated BV2 in vitro model were used. Longa's scare was used to observe neurological function. TTC staining and Nissl staining were used to evaluate brain injury. ELISA, qRT-PCR, Western blotting and immunofluorescent staining methods were used to detect cytokine concentration, mRNA level, protein expression and location. RESULTS: GSS treatment improves neurological function, reduces the volume of cerebral infarction, attenuates proinflammatory cytokines and inactivates the phosphorylation of JAK2 and STAT3 in I/RI rats. Furthermore, GSS increased the expression of α7nAChR. More importantly, the neuroprotective, anti-inflammatory and inhibiting JAK2/STAT3 signaling pathway effects of GSS were counteracted in the presence of alpha-bungarotoxin (α-BTX), an α7nAChR inhibitor, suggesting that α7nAChR is a potential target associated with the anti-inflammatory effects of GSS in the I/RI rats. GSS also inhibited BV2 cells from releasing IL-1ß via the α7nAChR pathway after LPS stimulation. CONCLUSION: GSS protects against cerebral I/RI through the expression of α7nAChR and inhibition of the JAK2/STAT3 pathway. Our findings provide evidence for the role of the cholinergic anti-inflammatory pathway in neuroinflammation and uncover a potential novel mechanism for GSS treatment in ischemic stroke. The downstream signals of GSS, α7nAChR- JAK2/STAT3 could also be potential targets for the treatment of I/RI.

Nanocarrier-delivered small interfering RNA for chemoresistant ovarian cancer therapy.

Ovarian cancer is the fifth leading cause of cancer-related death in women in the United States. Because success in early screening is limited, and most patients with advanced disease develop resistance to multiple treatment modalities, the overall prognosis of ovarian cancer is poor. Despite the revolutionary role of surgery and chemotherapy in curing ovarian cancer, recurrence remains a major challenge in treatment. Thus, improving our understanding of the pathogenesis of ovarian cancer is essential for developing more effective treatments. In this review, we analyze the underlying molecular mechanisms leading to chemotherapy resistance. We discuss the clinical benefits and potential challenges of using nanocarrier-delivered small interfering RNA to treat chemotherapy-resistant ovarian cancer. We aim to elicit collaborative studies on nanocarrier-delivered small interfering RNA to improve the long-term survival rate and quality of life of patients with ovarian cancer. This article is categorized under: RNA Methods > RNA Nanotechnology Regulatory RNAs/RNAi/Riboswitches > RNAi: Mechanisms of Action.

Effect of bone cement distribution on adjacent vertebral body fracture after unilateral percutaneous vertebroplasty for single segment osteoporotic vertebral compression fracture / 中国组织工程研究

BACKGROUND: Previous studies on the risk factors of adjacent vertebral fractures after percutaneous vertebroplasty at home and abroad mainly focus on the leakage of bone cement, the amount of bone cement injected, the viscosity of bone cement, the number and location of vertebral fractures, the loss of vertebral height and sex. OBJECTIVE: To predict and analyze the influence of bone cement distribution on adjacent vertebral body fracture after unilateral percutaneous vertebroplasty for single segment osteoporotic vertebral compression fracture. METHODS: Forty patients with single segment osteoporotic vertebral compression fracture, including 16 males and 24 females, aged (71.4 ±5.3) years who received percutaneous vertebroplasty in the Second Affiliated Hospital of Shanxi Medical University from June 2017 to June 2018 were included in this study. These patients were divided into a unilateral group (13 vertebrae in 13 cases) and a bilateral group (27 vertebrae in 27 cases) according to the distribution of bone cement shown on X-ray film. Patients in the unilateral group were sub-divided into groups A (8 vertebrae in 8 cases, contacting the upper and lower endplates at the same time) and B (5 vertebrae in 5 cases, not contacting the upper and lower endplates at the same time) according to whether bone cement contacted the upper and lower endplates at the same time. Patients in the bilateral group were sub-divided into groups C (11 vertebrae in 11 cases, contacting the upper and lower endplates at the same time) and D (16 vertebrae in 16 cases, not contacting with the upper and lower endplates at the same time). Visual analogue scale score, Oswestry disability index, and Cobb angle were compared between unilateral and bilateral groups before and 1 year after surgery. The compression rate between adjacent vertebral bodies and the angle between the upper and lower endplates were compared between groups A, B, C and D. This study was approved by the Medical Ethics Committee of the Second Affiliated Hospital of Shanxi Medical University. RESULTS AND CONCLUSION: (1) At 1 year after surgery, the Visual Analogue Scale score, Oswestry disability index, and Cobb angle in both unilateral and bilateral groups were significantly decreased compared with before surgery (P 0.05). (2) At 1 year after surgery, the compression rate between adjacent vertebral bodies in groups A-D was significantly increased compared with before surgery (P < 0.05), and the angle between the upper and lower endplates in groups A-D was significantly increased compared with before surgery (P < 0.05). (3) Disordered multiclass logistic regression analysis taking group D as reference showed that the compression degree of adjacent vertebrae in group A was the largest after percutaneous vertebroplasty, which was the risk factor of the compression change of adjacent vertebrae after surgery (P=0.003). Group B and group C were not the risk factors of the compression change of adjacent vertebrae after percutaneous vertebroplasty [P=0.065, 0.660]. (4) These results show that after percutaneous vertebroplasty, if bone cement is distributed unilaterally and closer to the upper and lower endplates of the vertebral body at the same time, then the trend of adjacent vertebral body fracture is greater. Therefore, prediction of bone cement distribution of this type is a risk factor of adjacent vertebral body fracture after percutaneous vertebroplasty.

3'-Daidzein Sulfonate Sodium Protects Against Chronic Cerebral Hypoperfusion-Mediated Cognitive Impairment and Hippocampal Damage via Activity-Regulated Cytoskeleton-Associated Protein Upregulation.

The learning and memory impairment caused by chronic cerebral hypoperfusion (CCH) is permanent and seriously affects the daily life of patients and their families. The compound 3'-daidzein sulfonate sodium (DSS) protects against CCH-mediated memory impairment and hippocampal damage in a rat model. In the present study, we further investigated the underlying mechanisms of this effect in the rat two-vessel occlusion (2VO) and the oxygen and glucose deprivation (OGD) primary hippocampal neuron models. The hippocampal expression of the activity-regulated cytoskeleton associated protein (Arc) following DSS administration was detected in vivo and in vitro and behavioral testing was used to investigate the role of Arc in the DSS-mediated rescue of CCH-induced neurotoxicity. DSS increased hippocampal Arc expression both in vivo and in vitro. Arc overexpression increased and Arc knockdown decreased hippocampal neuronal densities in rat 2VO model, when compared to DSS treatment alone. Arc overexpression decreased and Arc knockdown increased apoptotic hippocampal neurons in rat 2VO and OGD primary hippocampal neuron models, when compared to DSS treatment alone. Arc overexpression enhanced and Arc knockdown inhibited the beneficial effect of DSS on 2VO-induced cognitive impairment. DSS restored the neuronal OGD-mediated phosphorylation decrease in protein kinase alpha (PKA), extracellular signal-regulated protein kinases 1/2 (ERK1/2) and cAMP response element binding protein (CREB), in vitro. PKA and ERK1/2 inhibition blocked the DSS-mediated effects on neuronal apoptosis and OGD-induced Arc downregulation. In conclusion, DSS protects against CCH-mediated cognitive impairment and hippocampal damage via Arc upregulation, which is activated by the PKA/CREB and ERK/CREB signaling pathways. Our study further confirms the potential use of DSS as an effective treatment for CCH-associated diseases.

Tumor-Targeted and Biocompatible MoSe2 Nanodots@Albumin Nanospheres as a Dual-Modality Therapy Agent for Synergistic Photothermal Radiotherapy.

Integrating multiple tumor therapy functions into one nanoplatform has been a new tumor therapy strategy in recent years. Herein, a dual-modality therapy agent consisting of molybdenum selenide nanodots (MoSe2 NDs) and bovine serum albumin (BSA) assembled nanospheres (MoSe2@BSA NSs) was successfully synthesized. After conjugation of folic acid (FA) molecules via polyethylene glycol (PEG) "bridges," the FA-MoSe2@BSA NSs were equipped with tumor-targeting function. The BSA and PEG modifications provided the unstable MoSe2 NDs with excellent physiological stability. Since the end-product FA-MoSe2@BSA NSs had strong near-infrared (NIR) and X-ray absorbance properties, they exhibited good photothermal properties with excellent photothermal stability and radio-sensitization ability, hence, were explored as photothermal radiotherapy agents. In vitro and in vivo experiments indicated that the FA-MoSe2@BSA NSs possessed highly efficient tumor-targeting effect, great biocompability, and synergistic photothermal radiotherapy effect. This work suggests that such biocompatible FA-MoSe2@BSA NSs may be a promising multifunctional dual-modality tumor therapy agent for use in combination tumor therapy.

3'-Daidzein sulfonate sodium protects against memory impairment and hippocampal damage caused by chronic cerebral hypoperfusion.

3'-Daidzein sulfonate sodium (DSS) is a new synthetic water-soluble compound derived from daidzein, a soya isoflavone that plays regulatory roles in neurobiology. In this study, we hypothesized that the regulatory role of DSS in neurobiology exhibits therapeutic effects on hippocampal damage and memory impairment. To validate this hypothesis, we established rat models of chronic cerebral hypoperfusion (CCH) by the permanent occlusion of the common carotid arteries using the two-vessel occlusion method. Three weeks after modeling, rat models were intragastrically administered 0.1, 0.2, and 0.4 mg/kg DSS, once a day, for 5 successive weeks. The Morris water maze test was performed to investigate CCH-induced learning and memory deficits. TUNEL assay was used to analyze apoptosis in the hippocampal CA1, CA3 regions and dentate gyrus. Hematoxylin-eosin staining was performed to observe the morphology of neurons in the hippocampal CA1, CA3 regions and dentate gyrus. Western blot analysis was performed to investigate the phosphorylation of PKA, ERK1/2 and CREB in the hippocampal PKA/ERK1/2/CREB signaling pathway. Results showed that DSS treatment greatly improved the learning and memory deficits of rats with CCH, reduced apoptosis of neurons in the hippocampal CA1, CA3 regions and dentate gyrus, and increased the phosphorylation of PKA, ERK1/2, and CREB in the hippocampus. These findings suggest that DSS protects against CCH-induced memory impairment and hippocampal damage possibly through activating the PKA/ERK1/2/CREB signaling pathway.

3'-Daidzein sulfonate sodium provides neuroprotection by promoting the expression of the α7 nicotinic acetylcholine receptor and suppressing inflammatory responses in a rat model of focal cerebral ischemia.

In a previous study using a rat model of focal cerebral ischemia/reperfusion (I/R) injury, we found that 3'-Daidzein sulfonate sodium (DSS), a derivative of daidzein, exerts neuroprotective effects by alleviating brain edema and reducing levels of interleukin (IL)-6. The present study was designed to further examine the potential mechanisms of the neuroprotective properties of DSS in a rat model of cerebral I/R injury. We found that treatment with DSS ameliorated neurological deficit, infarct size, and cerebral water content in rats with cerebral I/R injury. Moreover, treatment with DSS significantly reduced the levels of IL-1ß, IL-6, and tumor necrosis factor (TNF)-α in serum and in the ischemic penumbra. Additionally, DSS treatment increased the expression of nicotinic acetylcholine receptor alpha 7 (α7nAChR), and inhibited the expression of glial fibrillary acidic protein, phosphorylated p65 nuclear factor κB, and phosphorylated inhibitor of NF-κBα, suggesting that DSS provides neuroprotection by suppressing inflammatory responses after focal cerebral I/R injury. Notably, α-bungarotoxin, an antagonist of α7nAChR, reversed the neuroprotective effects of DSS after cerebral I/R injury, suggesting that inhibition of α7nAChR expression is sufficient for reversal of the neuroprotective effects of DSS. In conclusion, we found that DSS treatment provides neuroprotection by promoting α7nAChR expression in a rat model of focal cerebral ischemia, thus establishing α7nAChR as a potential therapeutic target in cerebral I/R injury.

Dosimetric comparison and observation of three-dimensional conformal radiotherapy for recurrent nasopharyngeal carcinoma.

The aim of the study was to investigate the effect of three-dimensional conformal radiation therapy (3D-CRT) on nasopharyngeal carcinoma (NPC) and the incidence of complications. Between May 2010 and June 2012, 141 patients diagnosed with local recurrence of NPC due to cranial base lesions or cranial nerve symptoms, confirmed by pathology biopsy and/or by CT/MRI, were included in the present study. In accordance with the principle of randomized control, the patients were divided into three groups and treated with three different doses of 3D-CRT. The planned radiotherapy doses of 3D-CRT were 58/1.8-2 Gy, 62/1.8-2 Gy and 68/1.8-2 Gy, respectively. The survival rate, disease-free survival (DFS) rate and local control rate of the three groups of patients were compared as well as the adverse reactions observed after radiotherapy. The prognoses of NPC patients were analyzed by univariate and multivariate analyses. The follow-up rate of the study was 100%. The 5-year overall survival, DFS, and locoregional recurrence-free survival rates were: 43.2 vs. 64.53 vs. 75%, 29.13 vs. 42.82 vs. 39.7% and 30.76 vs. 44.19 vs. 45.4%, respectively. In addition, 62/1.8-2 Gy was similar in treatment effects to 68/1.8-2 Gy, but 68/1.8-2 Gy showed more adverse reactions than 62/1.8-2 Gy. Thus, 62/1.8-2 Gy can be used as a safe and effective dose for 3D-CRT treatment of NPC. Univariate and multivariate analyses showed that age may be the main prognostic factor of patients with NPC. In conclusion, 3D-CRT with a dose of 62/1.8-2 Gy is a safe, effective and tolerable treatment for NPC patients with good clinical value.

3'-Daidzein sulfonate sodium inhibits neuronal apoptosis induced by cerebral ischemia-reperfusion.

This study aimed to observe the effects of 3'-daidzein sulfonate sodium (DSS) on ischemia-reperfusion-induced brain injury and to analyze the mechanisms responsible for neuronal apoptosis. Focal ischemias were induced in male Sprague-Dawley rats using middle cerebral artery occlusion. The rats were divided into 5 groups based on sham surgery or real occlusion, and treatment with different doses of DSS (0.5, 1.0 and 2.0 mg/kg) or normal saline (model group), injected preoperatively into the rats with cerebral occlusion. After 2 h of ischemia and 24 h of reperfusion, neurological deficit scores were evaluated using the Longa grade point standard. The infarct volume was measured using a triphenyl tetrazolium chloride staining technique. Blood-brain barrier (BBB) permeability was measured using the Evans blue (EB) content of brain tissues, while electron microscopy was used to observe ultrastructural changes. The expression levels of Bcl-2, Bax and caspase-3 were detected by an immunohistochemical method and western blot analysis. The neurological deficit in rats pre-treated with DSS at all doses decreased significantly (P<0.05) in comparison with the model group, as did the cerebral infarct volume ratios. The brain EB content was significantly reduced by the injection of DSS. The ultrastructural integrity of the rat BBB was significantly preserved in the DSS-treated groups in comparison with the model group. This was concomitant with the reduced swelling of astrocytes and pericytes in the BBB. The immunohistochemistry results revealed that DSS significantly enhanced the expression of Bcl-2, and inhibited the expression of Bax and caspase-3 in the brain in comparison to the model group. The number of apoptotic cells in the groups treated with DSS was reduced in comparison with similar areas in the model group. These findings suggest that DSS within a dosage range of 0.5-2.0 mg/kg provides significant protection from injury to the BBB induced by cerebral ischemia-reperfusion, as it exerts a neuroprotective effect by inhibiting apoptosis.

Neuroprotective effects of genistein-3'-sodium sulfonate on focal cerebral ischemia in rats.

In order to improve the poor water solubility of genistein (4',5,7-trihydroxyisoflavone), which is extracted from food sources such as tofu, soybeans, and kudzu, we sulfonated genistein to synthesize a relatively more water-soluble compound, namely genistein-3'-sodium sulfonate (GSS). Our previous studies demonstrate that GSS protects cortical neurons from injury induced by focal cerebral ischemia. However, the molecular mechanisms underlying this protective effect remain unclear. We aimed to investigate the protective effect and potential molecular mechanisms of action of GSS in rat glutamate-induced cortical neuron injury in vitro and middle cerebral artery occlusion (MCAO) in vivo models. Our results showed that GSS exhibited a protective effect against glutamate-induced cytotoxicity in rat cortical neurons by reducing lactate dehydrogenase (LDH) release, inhibiting cell apoptosis, increasing Bcl-2/Bax expression ratio, and reducing Caspase 3 activity. GSS also decreased the infarcted area and neurological deficits in the rat MCAO model, reduced LDH release from the brain tissue to the serum, increased the Bcl-2/Bax expression ratio, and reduced Caspase 3 activity. These findings suggest that GSS protects rat cortical neurons from injury induced by focal cerebral ischemia in both in vitro and in vivo models, through increased Bcl-2/Bax expression ratio and reduced Caspase 3 activity.

Chitosan as a condensing agent induces high gene transfection efficiency and low cytotoxicity of liposome.

To enhance the transfection efficiency of the cationic liposomes, chitosan was selected as a DNA condensing agent. The particle size of the liposome/chitosan/DNA ternary complexes decreased and the zeta potential increased with the addition of chitosan. The formation of the ternary complexes was identified using agarose gel retardation study. The interaction of the ternary complexes was further confirmed by the decrease of the DNA fluorescence in the presence of [Ru(phen)2dppz](2+). In vitro and in vivo transfection activities of the complexes were determined using green fluorescent protein (GFP) expression in various cell lines and mouse tibial anterior muscle subcutaneously, respectively. Liposome/chitosan/DNA ternary complexes showed improved transfection efficiency in vitro cell culture system in the presence or absence of serum as well as in vivo mouse model system, as compared with liposome/DNA lipoplex. More importantly, the cell toxicity of the ternary complex is lower than that of lipoplex and liposome/poly-l-lysine/DNA ternary complex. The precondensation of DNA with chitosan can be a promising approach to further increase the transfection efficiency of cationic liposomes in clinical application.