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Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) combined with sensitizer is a potential method to reverse TRAIL-resistance in tumor cells. Rhein (RH) is a monomer extracted from Chinese herbs that has been reported to show anti-tumor effects in a variety of tumor cells, but the role of RH in TRAIL-induced anti-tumor effects in bladder cancer cells has not been reported. In this study, we found that the combined treatment of a non-toxic concentration of RH with TRAIL significantly inhibited the proliferation and induced apoptosis in both TRAIL sensitive and resistant bladder cancer cell lines. Furthermore, we found that RH promoted bladder cancer cell apoptosis by up-regulating DR5 expression. Our findings provide potential value in the clinical treatment of bladder cancer.

Chemotherapy continues to be the most commonly applied strategy for cancer. Despite the impressive clinical success obtained with several drugs, increasing numbers of (multi)drug-resistant tumors are reported. To overcome this shortcoming, novel drug candidates and delivery systems are urgently needed. Herein, a therapeutic copper polypyridine complex encapsulated in natural nanocarrier apoferritin is reported. The generated nanoparticles showed higher cytotoxicity toward various (drug-resistant) cancer cell lines than noncancerous cells. The study of the mechanism revealed that the compound triggers cell autophagy-dependent apoptosis. Promisingly, upon injection of the nanodrug conjugate into the bloodstream of a mouse model bearing a multidrug-resistant colon tumor, a strong tumor growth inhibition effect was observed. To date, this is the first study describing the encapsulation of a copper complex in apoferritin that acts by autophagy-dependent apoptosis.

OBJECTIVE: To investigate the effect of honokiol on demyelination after compressed spinal cord injury (CSCI) and it's possible mechanism. DESIGN: Animal experiment study. SETTING: Institute of Neuroscience of Chongqing Medical University. INTERVENTIONS: Total of 69 Sprague–Dawley (SD) rats were randomly divided into 3 groups: sham group (n=15), honokiol group (n=27) and vehicle group (n=27). After established CSCI model by a custom-made compressor successfully, the rats of sham group were subjected to the limited laminectomy without compression; the rats of honokiol group were subjected to CSCI surgery and intraperitoneal injection of 20 mg/kg honokiol; the rats of vehicle group were subjected to CSCI surgery and intraperitoneal injection of an equivalent volume of saline. Outcome measures: The locomotor function of each group was assessed using the Basso, Beattie and Bresnahan (BBB) rating scale. The pathological changes of myelinated nerve fibers of spinal cord in 3 groups were detected by osmic acid staining and transmission electron microcopy (TME). Immunofluorescence and Western blot were used to research the experessions of active caspase-3, caspase-12, cytochrome C and myelin basic protein (MBP) respectively. RESULTS: In the vehicle group, the rats became paralyzed and spastic after injury, and the myelin sheath became swollen and broken down along with decreased number of myelinated nerve fibers. Western blot analysis manifested that active caspase-3, caspase-12 and cytochrome C began to increase 1 d after injury while the expression of MBP decreased gradually. After intervened with honokiol for 6 days, compared with the vehicle group, the locomotor function and the pathomorphological changes of myelin sheath of the CSCD rats were improved with obviously decreased expression of active caspase-3, caspase-12 and cytochrome C. CONCLUSIONS: Honokiol may improve locomotor function and protect neural myelin sheat from demyelination via prevention oligodendrocytes (OLs) apoptosis through mediate endoplasmic reticulum (ER)-mitochondria pathway after CSCI.

The blood–brain barrier (BBB) is an essential component of the neurovascular unit that controls the exchanges of various biological substances between the blood and the brain. BBB damage is a common feature of different central nervous systems (CNS) disorders and plays a vital role in the pathogenesis of the diseases. Non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNA (lncRNAs), and circular RNAs (circRNAs), are important regulatory RNA molecules that are involved in almost all cellular processes in normal development and various diseases, including CNS diseases. Cumulative evidences have demonstrated ncRNA regulation of BBB functions in different CNS diseases. In this review, we have summarized the miRNAs, lncRNAs, and circRNAs that can be served as diagnostic and prognostic biomarkers for BBB injuries, and demonstrated the involvement and underlying mechanisms of ncRNAs in modulating BBB structure and function in various CNS diseases, including ischemic stroke, hemorrhagic stroke, traumatic brain injury (TBI), spinal cord injury (SCI), multiple sclerosis (MS), Alzheimer's disease (AD), vascular cognitive impairment and dementia (VCID), brain tumors, brain infections, diabetes, sepsis-associated encephalopathy (SAE), and others. We have also discussed the pharmaceutical drugs that can regulate BBB functions via ncRNAs-related signaling cascades in CNS disorders, along with the challenges, perspective, and therapeutic potential of ncRNA regulation of BBB functions in CNS diseases.

Vascular cognitive impairment and dementia (VCID) is defined as a progressive dementia disease related to cerebrovascular injury and often occurs in aged populations. Despite decades of research, effective treatment for VCID is still absent. The pathological processes of VCID are mediated by the molecular mechanisms that are partly modulated at the post‐transcriptional level. As small endogenous non‐coding RNAs, microRNAs (miRs) can regulate target gene expression through post‐transcriptional gene silencing. miRs have been reported to play an important role in the pathology of VCID and have recently been suggested as potential novel pharmacological targets for the development of new diagnosis and treatment strategies in VCID. In this review, we summarize the current understanding of VCID, the possible role of miRs in the regulation of VCID and attempt to envision future therapeutic strategies. Since manipulation of miR levels by either pharmacological or genetic approaches has shown therapeutic effects in experimental VCID models, we also emphasize the potential therapeutic value of miRs in clinical settings., miR regulatory mechanisms in experimental VCID.

Chondroblastoma is a rare, benign, cartilaginous-derived tumor accounting for ∼1% to 2% of all primary bone tumors and almost 9% of all benign bone tumors. In this case report, we describe a patient with chondroblastoma and a secondary aneurysmal bone cyst, with the adjacent talus being mildly affected. The initial diagnosis was giant cell tumor and was then confirmed after computed tomography-assisted biopsy. We performed a total calcanectomy via bilateral structural iliac bone autografting to relieve pain and reconstruct the loadbearing function because of the presence of extensive lesions. The patient was pain free and expressed satisfaction with postsurgical dorsiflexion and plantarflexion function at the 60-month follow-up visit. Radiographic images showed that the autografted iliac bone was completely healed, with no evidence of local recurrence.

Although the phosphorylation of 4E-BP1 that has been detected in high-grade prostate cancer has been reported in previous studies, overexpression of p4E-BP1 and 4EBP1 and their clinical significance in prostate cancer still remain unknown.One hundred six samples of prostate tissues were collected and analyzed by immunohistochemistry with p4E-BP1 or 4E-BP1 specific antibodies. Everolimus was used to block the phosphorylation of p4E-BP1, and then flow cytometry, clone formation, transwell, and wound healing assays were performed to detect the survival and invasive ability of the prostate cancer cells.We found that the expression of 4E-BP1 and p4E-BP1 was higher in prostate cancer tissues than in normal tissues. Interestingly, the expression of p4E-BP1 was significantly associated with Gleason score and lymph node metastasis, but had no obvious correlation with PSA and the presence of bone or visceral metastasis. However, no evident correlation was found between the positive expression of 4E-BP1 and these clinical characteristics. In in vitro experiments, we found similar results as the clinical presentation that 4E-BP1 and p4E-BP1 were low expressed in normal prostate epithelial cells, but in prostate cancer cells, as the malignancy increasing, 4E-BP1 and p4E-BP1 expression also gradually increased. Then, we used Everolimus to inhibit the phosphorylation of 4E-BP1 and found that Everolimus effectively reduced cloning formation, inhibited cell migration, and promoted apoptosis in a dose-dependent manner in PC3 cells.These findings suggest that p4E-BP1 is a potential biomarker and therapy target for prostate cancer, and patients with high expressions of p4E-BP1 may benefit from Everolimus treatment.

Background Periprosthetic joint infection (PJI) is considered to be one of the most challenging complications of joint replacement, which remains unpredictable. As a simple and emerging biomarker, calprotectin (CLP) has been considered to be useful in ruling out PJI in recent years. The purpose of this study was to investigate the accuracy and sensitivity of CLP in the diagnosis of PJI. Methods We searched and screened the publications from PubMed, Web of Science, EMBASE, and Cochrane Library from database establishment to June 2021. Subsequently, Stata version 16.0 software was used to combine the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), operating characteristic curve, and area under the curve (AUC). Heterogeneity across articles was evaluated by the I2 statistics. Finally, sources of heterogeneity were detected by subgroup analysis based on study design, detection method, sample size, and cutoff values. Results A total of 7 studies were included in our study, comprising 525 patients. The pooled sensitivity, specificity, PLR, and NLR of CLP for PJI diagnosis were 0.94(95% CI 0.87–0.98), 0.93(95% CI 0.87–0.96), 13.65(95% CI 6.89–27.08), and 0.06(95% CI 0.02–0.15), respectively, while the DOR and AUC were 222.33(95% CI 52.52–941.11) and 0.98 (95% CI 0.96–0.99), respectively. Conclusion Synovial CLP is a reliable biomarker and can be used as a diagnostic criterion for PJI in the future. However, the uncertainty resulting from the poor study numbers and sample sizes limit our ability to definitely draw conclusions on the basis of our study.

BackgroundA retrospective study was conducted to evaluate and compare the clinical and radiological outcomes of one-stage fibular impaction allografting and vascularized greater trochanter flap autografting for the treatment of bilateral osteonecrosis of the femoral head (ONFH).MethodsPatients who underwent one-stage aforementioned hip-preserving surgeries due to bilateral ONFH were retrospectively reviewed from January 2008 to December 2013. Sixty-nine patients (138 hips) with a mean age of 31.5 years and mean follow-up of 7.0 years were included. Hips that underwent fibular impaction allografting and vascularized greater trochanter flap autografting were assigned as group A and group B, respectively. Harris Hip Score (HHS) and Visual Analogue Scale (VAS) were used for clinical evaluation, and a series of X-ray images were used for radiological assessment. For inter-group analysis, the pairedttest was used for continuous data, and the Wilcoxon rank sum test was used for non-parametric data, while the Mann-WhitneyUtest was used for intra-group analysis.ResultsThe HHS and VAS in both groups A and B had a substantial advancement when compared with the preoperative level (p p p = 0.04). It was discovered that the appropriate indication for each procedure was patients with Association for Research on Osseous Circulation (ARCO) stages II and III, respectively.ConclusionOne-stage hip-preserving surgeries for the management of bilateral ONFH could obtain good medium and long-term outcomes. It was recommended that fibular impaction allografting is more suitable for patients in ARCO stage II, while for patients in ARCO stage III, vascularized greater trochanter flap autografting is a better preference.Trial registrationRetrospectively registered.

Antibiotic-loaded bone cement (ALBC) was usually used to prevent periprosthetic joint infection (PJI) in primary total knee arthroplasty (PTKA), but whether to use ALBC or plain bone cement in PTKA remains unclear. We aimed to compare the occurrence rate of PJI using two different cements, and to investigate the efficacy of different antibiotic types and doses administered in preventing surgical site infection (SSI) with ALBC.The availability of ALBC for preventing PJI was evaluated by using a systematic review and meta-analysis referring to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Existing articles until December 2021 involving PTKA patients with both ALBC and plain bone cement cohorts were scanned by searching "total knee arthroplasty", "antibiotic-loaded cement", "antibiotic prophylaxis", "antibiotic-impregnated cement" and "antibiotic-laden cement" in the database of PubMed/MEDLINE, Embase, Web of Science and the Cochrane Library. Subgroup analysis included the effectiveness of different antibiotic types and doses in preventing SSI with ALBC. The modified Jadad scale was employed to score the qualities of included articles.Eleven quantitative studies were enrolled, including 34,159 knees undergoing PTKA. The meta-analysis results demonstrated that the use of prophylactic ALBC could significantly reduce the prevalence of deep incisional SSI after PTKA, whereas there was no significant reduction in the rate of superficial incisional SSI. Moreover, gentamicin-loaded cement was effective in preventing deep incisional SSI, and the use of high-dose ALBC significantly reduced the rate of deep incisional SSI after PTKA. Besides, no significant adverse reactions and complications were stated during the use of ALBC in PTKA.The preventive application of ALBC during PTKA could reduce the rates of deep PJI. Furthermore, bone cement containing gentamicin and high-dose ALBC could even better prevent deep infection after PTKA. However, the existing related articles are mostly single-center and retrospective studies, and further high-quality ones are needed for confirmation.

Small cell lung cancer (SCLC) is the most malignant type of lung cancer. We previously reported that arsenic trioxide (AsTICs were enriched by culturing human SCLC cell line as sphere cells in specified serum-free medium. The expression of stem cell markers, CD133 and CD44, and the in vivo tumorigenicity of both TICs and their parental cells were examined. To demonstrate the inhibitory effect of AsOur data demonstrate that As

Background To compare the mid-long-term clinical and radiological outcomes between a combination of cortico-cancellous iliac bone graft with vascularized greater trochanter flap (Group A) and isolate iliac bone graft (Group B) in the treatment of Osteonecrosis of the Femoral Head (ONFH). Methods From January 2006 to December 2012, 123 patients (135 hips) who underwent abovementioned hip-preserving surgeries were included for analysis. Clinical outcomes were assessed based on Harris Hip Score (HHS) System and The Western Ontario and McMaster University Index (WOMAC) scores between the preoperative and the last follow-up. A series of postoperative X-rays were compared to preoperative images for radiological evaluation. Results The HHS in Group A and B were enhanced from 50.57 ± 3.39 to 87.60 ± 4.15 and from 50.24 ± 3.30 to 85.18 ± 6.45, respectively, which both showed significance between preoperative and postoperative latest follow-up (p 0.05). Conclusions A combination of cortico-cancellous iliac bone graft and concurrent vascularized greater trochanter flap with the lateral femoral circumflex transverse branch has been proved can obtain better functional and radiological results than isolate iliac bone grafting, which is attributed to blood reconstruction of the femoral head.

Background Nitrogen availability is an important environmental factor that determines the production of phenolic compounds in vegetables, but the relationship between low nitrogen-induced alterations of phenolic compounds in vegetable crops and the cellular antioxidant activities of these compounds remains unclear. This study investigated the effect of reduced nitrogen supply (0.05 mmol L-1 nitrate) on phenolic metabolism in lettuce and the protective role of phenolic extracts against H2 O2 -induced oxidative stress in Caco-2 cells by determining cell damage, reactive oxygen species (ROS) content and antioxidant enzyme activities. Results Reduced nitrogen supply significantly improved the accumulation of phenolic compounds in lettuce, which was partially correlated with the upregulation of genes related to the phenolic synthesis pathway. Phenolic extracts from lettuce cultivated in low-nitrogen medium exhibited a better protective effect against H2 O2 -induced oxidative damage in Caco-2 cells than those from lettuce cultivated with adequate nitrogen. These extracts act by increasing the activities of antioxidant enzymes and, subsequently, by inhibiting ROS overproduction, which leads to a decrease in mitochondrial membrane and DNA damage. The results of HPLC and correlation analyses implied that the improvement in the protective capacity of lettuce extracts after low-nitrogen treatment may be related, not only to the increased content of phenolic compounds, but also to the increased percentage contribution of chlorogenic acid and quercetin derivatives to the total phenolic content. Conclusion Reduction in nitrogen supply can be a powerful strategy to modify phenolic metabolism and composition in lettuce and, consequently, to improve their antioxidant capacity. © 2019 Society of Chemical Industry.

BACKGROUND High-mobility group box 1 (HMGB1) is an essential contributor towards initiation and progression of many kinds of cancers. Nevertheless, our understanding of the molecular etiology of HMGB1-modulated vasculogenesis, as well as invasion, of breast cancer is poor. This study explored HMGB1 expression in breast cancer and its role in the development and spread of malignancy. MATERIAL AND METHODS We enrolled 15 patients with breast cancer who received primary surgery at the Department of Thyroid and Breast Surgery in our hospital. HMGB1 was recorded and analyzed. RESULTS Our investigation successfully proves that HMGB1 is upregulated in breast cancer tissues in comparison to the surrounding non-malignant tissues. HMGB1 enhanced vessel formation in breast cancer tissues by regulating hypoxia-inducible factor 1 (HIF-1alpha), which in turn upregulates the expression of VEGF. Furthermore, HMGB1-mediated upregulation of HIF-1alpha relies on its ability to stimulate the phosphatidylinositol 3-kinase (PI3K) pathway to reinforce AKT subunit phosphorylation. HMGB1 overexpression reinforces the vasculogenesis in malignancies not only in vivo but also in vitro. Additionally, shRNA knockdown of HMGB1 prohibited the vessel-forming and invasive capabilities, downregulated VEGF and HIF-1alpha, and suppressed AKT phosphorylation in breast cancer cells. Most importantly, PI3K/AKT axis suppression eliminated the effect of HMGB1-modulated vascularization and invasion in breast cancer cells. CONCLUSIONS Our research indicates that HMGB1 serves as a crucial regulator of malignant cell-modulated vessel formation and is involved in the development of malignancy. Our findings indicate that HMGB1 is a promising target for breast cancer treatment.

Cerebral angiogenesis is tightly controlled by specific microRNAs (miRs), including the miR-15a/16-1 cluster. Recently, we reported that endothelium-specific conditional knockout of the miR-15a/16-1 cluster (EC-miR-15a/16-1 cKO) promotes post-stroke angiogenesis and improves long-term neurological recovery by increasing protein levels of VEGFA, FGF2, and their respective receptors VEGFR2 and FGFR1. Herein, we further investigated the underlying signaling mechanism of these pro-angiogenic factors after ischemic stroke using a selective Src family inhibitor AZD0530. EC-miR-15a/16-1 cKO and age- and sex-matched wild-type littermate (WT) mice were subjected to 1 h middle cerebral artery occlusion (MCAO) and 28d reperfusion. AZD0530 was administered daily by oral gavage to both genotypes of mice 3-21d after MCAO. Compared to WT, AZD0530 administration exacerbated spatial cognitive impairments and brain atrophy in EC-miR-15a/16-1 cKO mice following MCAO. AZD0530 also attenuated long-term recovery of blood flow and inhibited the formation of new microvessels, including functional vessels with blood circulation, in the penumbra of stroked cKO mice. Moreover, AZD0530 blocked the Src signaling pathway by downregulating phospho-Src and its downstream mediators (p-Stat3, p-Akt, p-FAK, p-p44/42 MAPK, p-p38 MAPK) in post-ischemic brains. Collectively, our data demonstrated that endothelium-targeted deletion of the miR-15a/16-1 cluster promotes post-stroke angiogenesis and improves long-term neurological recovery via activating Src signaling pathway.

Background Osteonecrosis of the femoral head (ONFH) is a disabling disease, which often involves young patients. Recently, various hip-preserving surgeries were recommended to delay total hip arthroplasty (THA). Questions/purposes This study aimed to compare clinical outcomes and survival rate in the long-term follow-up between core decompression combined with a non-vascularized autologous fibular graft (group A) and an allogeneic fibular graft (group B) for the treatment of ONFH. Patients and methods We retrospectively evaluated 117 patients (153 hips) with ONFH (Association Research Circulation Osseous [ARCO] stages IIa to IIIc) who underwent the abovementioned hip-preserving surgeries between January 2003 and June 2012. The mean (range) follow-up times (years) were 12.9 (7–16) and 9.3 (6–16) in groups A and B, respectively. Clinical outcomes were assessed using the Harris Hip Score (HHS), visual analog scale (VAS) score, and forgotten joint score (FJS). A survival analysis was performed using the Kaplan-Meier method. The end point was THA. Results Groups A and B showed postoperative improvements, respectively, in HHS from 65 ± 7.2 to 80.3 ± 14.5 and from 66 ± 5.9 to 82.4 ± 13.6 (p p p > 0.05) and 15-year survival rate (84.1% and 86%, respectively, p > 0.05) were found between groups A and B. Conclusions Autologous and allogeneic fibular grafts can attain equally good clinical outcomes and high survival rates in long-term follow-up, and thus can greatly delay THA owing to good bone osseointegration and sufficient mechanical support. Notably, the ratio of failure will increase when patients were more than 37 years old. Level of evidence Level III, therapeutic study

Background: Renal cell carcinoma (RCC) is a tumor with unpredictable presentation and poor clinical outcome. RCC is always resistant to chemotherapy, radiation, and weakly sensitive to immunotherapeutic agents. Therefore, novel agents and approaches are urgently needed for the treatment of RCC. Emodin, an anthraquinone compound extracted from rhubarb and other traditional Chinese herbs, has been implicated in a wide variety of pharmacological effects, such as anti-inflammatory, antiviral, and antitumor activities. However，its role in RCC remains unkown. Methods: Flow cytometry assay and lactate dehydrogenase release assay were used to detect the cell death. Reactive oxygen species was tested by the dye MitoSox and DCFH-DA. Glucose-6-phosphate, pyruvate and ATP level were measured to evaluate the glycolysis process. Western blot was used to detect protein expression. Results: Emodin effectively killed renal cancer cells without significant toxicity to normal renal tubular epithelial cell. Flow cytometry assay with Annexin V-FITC and PI demonstrated that emodin induces necroptosis, but not apoptosis, in renal cancer cells. Meanwhile, the phosphorylation levels of RIP1 and MLKL, the key necroptosis-related proteins, were significantly increased. To explore how emodin inhibits kidney tumor growth, reactive oxygen species (ROS) levels were tested and the levels of ROS increased upon emodin treatment in a dose-dependent manner. Further studies demonstrated that emodin induced necroptosis through ROS-mediated activation of JNK signaling pathway, and also inhibited glycolysis by down-regulation GLUT1 by ROS-mediated inactivation of PI3K/AKT signaling pathway. Conclusion: These findings revealed the potential mechanisms by which emodin suppresses renal cancer cell growth, and will help develop novel therapeutic approaches for patients with JNK- or PI3K/AKT-dysregulated renal cancer.

Background: The discovery that much of the non–protein-coding genome is transcribed and plays a diverse functional role in fundamental cellular processes has led to an explosion in the development of tools and technologies to investigate the role of these noncoding RNAs in cardiovascular health. Furthermore, identifying noncoding RNAs for targeted therapeutics to treat cardiovascular disease is an emerging area of research. The purpose of this statement is to review existing literature, offer guidance on tools and technologies currently available to study noncoding RNAs, and identify areas of unmet need. Methods: The writing group used systematic literature reviews (including MEDLINE, Web of Science through 2018), expert opinion/statements, analyses of databases and computational tools/algorithms, and review of current clinical trials to provide a broad consensus on the current state of the art in noncoding RNA in cardiovascular disease. Results: Significant progress has been made since the initial studies focusing on the role of miRNAs (microRNAs) in cardiovascular development and disease. Notably, recent progress on understanding the role of novel types of noncoding small RNAs such as snoRNAs (small nucleolar RNAs), tRNA (transfer RNA) fragments, and Y-RNAs in cellular processes has revealed a noncanonical function for many of these molecules. Similarly, the identification of long noncoding RNAs that appear to play an important role in cardiovascular disease processes, coupled with the development of tools to characterize their interacting partners, has led to significant mechanistic insight. Finally, recent work has characterized the unique role of extracellular RNAs in mediating intercellular communication and their potential role as biomarkers. Conclusions: The rapid expansion of tools and pipelines for isolating, measuring, and annotating these entities suggests that caution in interpreting results is warranted until these methodologies are rigorously validated. Most investigators have focused on investigating the functional role of single RNA entities, but studies suggest complex interaction between different RNA molecules. The use of network approaches and advanced computational tools to understand the interaction of different noncoding RNA species to mediate a particular phenotype may be required to fully comprehend the function of noncoding RNAs in mediating disease phenotypes.

To facilitate the cell-based experiment for pulsed electromagnetic field biological effect study, a novel TEM-cell-integrated CO

To observe the therapeutic effect of acupuncture on cancer-related fatigue (CRF) and to explore its possible mechanism.A total of 80 patients with CRF were randomized into an observation group and a control group, and finally 67 patients completed the trial (36 patients in the observation group, 31 patients in the control group). Patients in the control group were treated with conventional chemoradiotherapy and symptomatic treatment, while no particular anti-fatigue intervention was adopted. On the basis of treatment in the control group, acupuncture was applied at Baihui (GV 20), Guanyuan (CV 4), Qihai (CV 6), Fengchi (GB 20), Zusanli (ST 36), Sanyinjiao (SP 6) in the observation group, once a day, 5 times as one course, with 2 days interval between each course, totally 4 courses were required. Before and after treatment, scores of functional assessment of cancer therapy-fatigue (FACT-F) in Chinese and McGill quality of life questionnaire (MQOL), serum levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α) and soluble TNF receptor-1 (sTNF-R1) were observed in the two groups.①Compared before treatment, the FACT-F score was decreased after treatment in the observation group (①Acupuncture can improve the related symptoms of depression, weakness and headache in patients with CRF, strengthen their cognition of the support from society and family, and boost the confidence in curing the disease. ②Acupuncture can effectively down-regulate serum levels of the relative inflammatory factors, which may be its possible mechanism on treating CRF.

Objectives To investigate the value of a post-operative gait training program to improve pelvic obliquity (PO) and decrease leg length discrepancy (LLD) for patients with Crowe type I developmental dysplasia of the hip (DDH) undergoing unilateral total hip arthroplasty (THA). Methods The prospective group consisted of 35 patients who underwent one-stage unilateral THA. Pre- and post-training PO and LLD were measured for the radiological assessment and Harris Hip Score (HHS) was used for the functional assessment. Results The HHS improved from 55.54 ± 10.61 pre-operatively to 84.97 ± 7.63 after surgery. The mean post-training PO angle for grade 0, grade 1, and grade 2 were 2.66 ± 1.42, 2.94 ± 1.42, and 5.60 ± 1.90, respectively, compared with pre-training values of 1.42 ± 0.58, 4.17 ± 0.90, and 6.96 ± 0.46. The mean post-training LLD for grade 0, grade 1, and grade 2 were 0.83 ± 0.91, 0.56 ± 0.48, and 0.36 ± 0.30, respectively, compared with pre-training values of 0.70 ± 0.23, 1.25 ± 0.90, and 1.46 ± 1.60. Conclusion Gait training following unilateral THA can improve PO and decrease functional LLD in grade I DDH patients. This method may have moderate success for grade 0 DDH patients and provide limited benefit for grade II patients. Appropriate release of the soft tissues may be required for grade II DDH patients to obtain a better walking gait.

Mycotoxins are a group of secondary fungi metabolites present in foods that cause adverse effects in humans and animals. The objective of this study was to develop and validate a reliable and sensitive method to determine the presence of fumonisin B1, aflatoxin B1, ochratoxin B, T-2 toxin, ochratoxin A and zearalenone. A rapid, effective process, which involves microwave-assisted dispersive micro-solid phase extraction (MA- d -μ-SPE), has been proposed for the extraction and detection of 6 mycotoxins in peach seed, milk powder, corn flour and beer sample matrixes, for subsequent analysis by ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UHPLC-Q-TOF/MS). Several experimental parameters (type of dispersant, concentration of dispersant, vortex time, type of desorption solvent and pH) affecting the extraction efficiency were systematically studied and optimized. The optimum extraction conditions involved immersing 2.5 μg/mL of nano zirconia (as dispersant) in a 5 mL sample solution. After 2 min of extraction by vigorous shaking, the target analytes were desorbed by 100 μL of chloroform at pH 4.5. The results indicated good linearity in the range of 0.0074-3.6 μg/mL (r ≥ 0.9982), low limits of detection (0.0036-0.033 μg/kg for solid samples and 0.0022–0.017 ng/mL for beer), acceptable reproducibility (relative standard deviation (RSD%) 2.08–2.76% for retention time and 3.51–4.59% for peak area, n = 3), and satisfactory spiked recoveries (84.27–104.96%) for studied mycotoxins in sample matrixes, which demonstrated that MA- d -μ-SPE coupled with UHPLC-Q-TOF/MS is a useful tool for analysis of multi-mycotoxin.

Abdominal aortic aneurysm (AAA) is a vascular disorder with a high case fatality rate in the instance of rupture. AAA is a multifactorial disease, and the etiology is still not fully understood. AAA is more likely to occur in men, but women have a greater risk of rupture and worse prognosis. Women are reportedly protected against AAA possibly by premenopausal levels of estrogen and are, on average, diagnosed at older ages than men. Here, we review the present body of research on AAA pathophysiology in humans, animal models, and cultured cells, with an emphasis on sex differences and sex steroid hormone signaling.

Peroxisome proliferator-activated receptor γ (PPARγ) is a widely expressed ligand-modulated transcription factor that governs the expression of genes involved in inflammation, redox equilibrium, trophic factor production, insulin sensitivity, and the metabolism of lipids and glucose. Synthetic PPARγ agonists (e.g. thiazolidinediones) are used to treat Type II diabetes and have the potential to limit the risk of developing brain injuries, such as stroke, by mitigating the influence of comorbidities. If brain injury develops, PPARγ serves as a master gatekeeper of cytoprotective stress responses, improving the chances of cellular survival and recovery of homeostatic equilibrium. In the acute injury phase, PPARγ directly restricts tissue damage by inhibiting the NFκB pathway to mitigate inflammation and stimulating the Nrf2/ARE axis to neutralize oxidative stress. During the chronic phase of acute brain injuries, PPARγ activation in injured cells culminates in the repair of gray and white matter, preservation of the blood-brain barrier, reconstruction of the neurovascular unit, resolution of inflammation, and long-term functional recovery. Thus, PPARγ lies at the apex of cell fate decisions and exerts profound effects on the chronic progression of acute injury conditions. Here, we review the therapeutic potential of PPARγ in stroke and brain trauma and highlight the novel role of PPARγ in long-term tissue repair. We describe its structure and function and identify the genes that it targets. PPARγ regulation of inflammation, metabolism, cell fate (proliferation/differentiation/maturation/survival), and many other processes also has relevance to other neurological diseases. Therefore, PPARγ is an attractive target for therapies against a number of progressive neurological disorders.

Central nervous system (CNS) injuries are one of the leading causes of morbidity and mortality worldwide, accompanied with high medical costs and a decreased quality of life. Brain vascular disorders are involved in the pathological processes of CNS injuries and might play key roles for their recovery and prognosis. Recently, increasing evidence has shown that long non-coding RNAs (lncRNAs), which comprise a very heterogeneous group of non-protein-coding RNAs greater than 200 nucleotides, have emerged as functional mediators in the regulation of vascular homeostasis under pathophysiological conditions. Remarkably, lncRNAs can regulate gene transcription and translation, thus interfering with gene expression and signaling pathways by different mechanisms. Hence, a deeper insight into the function and regulatory mechanisms of lncRNAs following CNS injury, especially cerebrovascular-related lncRNAs, could help in establishing potential therapeutic strategies to improve or inhibit neurological disorders. In this review, we highlight recent advancements in understanding of the role of lncRNAs and their application in mediating cerebrovascular pathologies after CNS injury.

Background and objectives The survival rate of patients with advanced oesophageal cancer is very low and can vary significantly, even among patients with the same TNM stage. It is important to look for indicators that are economical and readily available to predict overall survival. The aim of this study was to determine whether lymphocyte-to-monocyte ratio (LMR) and neutrophil-to-lymphocyte ratio (NLR) could be potential predictors of survival in patients with advanced oesophageal squamous cell carcinoma (ESCC) undergoing concurrent chemoradiotherapy. Methods Differences in survival among 204 patients with advanced oesophageal cancer who underwent concurrent chemoradiotherapy were collected and analysed. Univariate and multivariate COX regression analyses were used to investigate the association between blood inflammatory markers and patient survival before treatment. Results Univariate COX regression analyses showed that a history of alcohol use, neutrophil count, LMR, NLR, tumour length, and N stage were significantly associated with the survival of tumour patients receiving concurrent chemoradiotherapy. Multivariate COX regression analysis showed that NLR and LMR were predictors of outcome in tumour patients receiving chemoradiotherapy. According to receiver operating characteristic (ROC) curve analysis, the AUC of LMR and NLR was 0.734 and 0.749, and the best cutoff point for LMR and NLR was 3.03 and 2.64, respectively. Conclusions LMR and NLR can be used to predict the survival of patients with advanced oesophageal cancer receiving concurrent chemoradiotherapy, thereby providing clinicians with suggestions for further treatment options.

BACKGROUND The inhibitory effect of arsenic trioxide (As₂O₃) on lung cancer has been reported in some preclinical studies. However, its effect on small cell lung cancer (SCLC) has been poorly explored. Calcineurin and its substrate, nuclear factor of activated T cells (NFAT), mediate the downstream signaling of VEGF, and is critical in the process endothelium activation and tumor metastasis. In this study, we aimed to evaluate whether As₂O₃ had inhibitory effects on endothelial cells activation and the metastasis of SCLC, and to explore the possible mechanisms. MATERIAL AND METHODS In vitro, human umbilical vein endothelial cells (HUVECs) were used. Cell Counting Kit-8 assay and cell migration assay were performed to determine the effect of As₂O₃ on HUVECs proliferation and migration. The level of calcineurin, NFAT, downstream factors for Down syndrome candidate region 1 (DSCR1), and the endogenous inhibitor of calcineurin, were evaluated by quantitative PCR and western blotting. In vivo, SCLC metastasis models were established by injecting NCI-H446 cells into tail veins of nude mice. Tumor-bearing mice were treated with As₂O₃ or calcineurin inhibitor for 10 days, after which tumor metastasis in target organs was evaluated. RESULTS As₂O₃ significantly inhibited the proliferation and migration of endothelial cells. Also, As₂O₃ inhibited the expression levels of calcineurin, NFAT, and the downstream target genes CXCR7 and RND1, while it upregulated the level of DSCR1. Both As₂O₃ and calcineurin inhibitor exhibited notable inhibitory effect on the metastasis of SCLC, without obvious side effects. CONCLUSIONS These findings suggested that As₂O₃ had remarkable inhibitory effects on the endothelial cell activation and SCLC metastasis, and the mechanism might be related to the blocking of calcineurin-NFAT signaling by upregulating DSCR1.

Background The number of periprosthetic joint infections (PJI) after total knee arthroplasty (TKA) is increasing annually. Animal models have been used to clarify their clinical characteristics and the infection mechanism of pathogenic bacteria, However, since the prosthesis design of animal models is not uniform, it is difficult to simulate the environment of clinical PJI. Objectives To retrospect the progress on the prosthesis design of animal models of PJI after TKA and to summarize the criteria for evaluating a clinically representative model of PJI. Methods This systematic review was reported on the basis of Systematic Reviews and Meta-Analyzes (PRISMA). Pubmed, EMbase, Cochrane Library, Web of Science, Wanfang Data and China National Knowledge Infrastructure were researched for animal models of PJI after TKA from database establishment to April 2019 according to Chinese and English retrieval words, including "periprosthetic joint infections and total knee arthroplasty," "periprosthetic joint infections and model," "periprosthetic joint infections and biofilm," and "total knee arthroplasty and model." Results A total of 12 quantitative studies were enrolled in our study finally: 8 representative studies described prosthesis designs used in PJI animal models, 4 studies described prosthesis designs in non-infected animal models which were suitable for infection models. The major problems need to be dealed with were prosthesis, installation location, material, the function of separating the articular and medullary cavity, fixation manner, and the procedure of preserving the posterior cruciate ligament. Conclusion A highly representative design of the animal prosthesis of PJI should meet the following criteria: the surface of the prosthesis is smooth with the formation of biofilm, composed of titanium-6Al-4V or cobalt-chromium-molybdenum alloy; prosthesis can bear weight and is highly stable; and it can connect the joint cavity and medullary cavity simultaneously. To reach a more reliable conclusion, further experiments and improvements are required.

Small-cell lung cancer (SCLC) is a highly malignant type of lung cancer with no effective second-line chemotherapy drugs. Arsenic trioxide (As2O3) was reported to exert antiangiogenesis activities against lung cancer and induce poor development of vessel structures, similar to the effect observed following the blockade of Notch signaling. However, there are no direct evidences on the inhibitory effects of As2O3on tumor growth and angiogenesis via blockade of Notch signaling in SCLC. Here, we found that As2O3significantly inhibited the tumor growth and angiogenesis in SCLC and reduced the microvessel density. As2O3disturbed the morphological development of tumor vessels and downregulated the protein levels of delta-like canonical Notch ligand 4 (Dll4), Notch1, and Hes1in vivo. DAPT, a Notch signaling inhibitor, exerted similar effects in SCLC. We found that both As2O3treatment andNotch1expression knockdown resulted in the interruption of tube formation by human umbilical vein endothelial cells (HUVECs) on Matrigel. As2O3had no effects on Dll4 level in HUVECs but significantly inhibited the expression ofNotch1and its downstream geneHes1regardless of Dll4 overexpression or Notch1 knockdown. These findings suggest that the antitumor activity of As2O3in SCLC was mediated via its antiangiogenic effect through the blockade of Notch signaling, probably owing to Notch1 targeting.

Given the essential role of the blood-brain barrier (BBB) in the central nervous system (CNS), cumulative investigations have been performed to elucidate how modulation of BBB structural and functional integrity affects the pathogenesis of CNS diseases such as stroke, traumatic brain injuries, dementia, and cerebral infection. Recent studies have demonstrated that microRNAs (miRNAs) contribute to the maintenance of the BBB and thereby mediate CNS homeostasis. This review summarizes emerging studies that demonstrate cerebral miRNAs regulate BBB function in CNS disorders, emphasizing the direct role of miRNAs in BBB molecular composition. Evidence presented in this review will encourage a deeper understanding of the mechanisms by which miRNAs regulate BBB function, and facilitate the development of new miRNAs-based therapies in patients with CNS diseases.

Central nervous system (CNS) injuries, such as stroke, traumatic brain injury (TBI) and spinal cord injury (SCI), are important causes of death and long-term disability worldwide. MicroRNA (miRNA), small non-coding RNA molecules that negatively regulate gene expression, can serve as diagnostic biomarkers and are emerging as novel therapeutic targets for CNS injuries. MiRNA-based therapeutics include miRNA mimics and inhibitors (antagomiRs) to respectively decrease and increase the expression of target genes. In this review, we summarize current miRNA-based therapeutic applications in stroke, TBI and SCI. Administration methods, time windows and dosage for effective delivery of miRNA-based drugs into CNS are discussed. The underlying mechanisms of miRNA-based therapeutics are reviewed including oxidative stress, inflammation, apoptosis, blood–brain barrier protection, angiogenesis and neurogenesis. Pharmacological agents that protect against CNS injuries by targeting specific miRNAs are presented along with the challenges and therapeutic potential of miRNA-based therapies.

A de novo designed intramolecular disulfide bond in myoglobin, resembling that in cytoglobin without structural evidence, was confirmed by an X-ray structure for the first time and was demonstrated to regulate both the structure and function of this protein, which fulfills the design of an artificial dehaloperoxidase, with an activity exceeding that of a native enzyme.

Rupture of an intracranial aneurysm is a life-threatening acute cerebrovascular event. The purpose of this study was to investigate whether aneurysmal subarachnoid haemorrhage (SAH) incidence rate is higher or lower in elderly population than in middle aged population.Aneurysmal SAH cases were collected retrospectively from the archives of 21 hospitals in Mainland China. All the cases were collected from September 2016 and backward consecutively for a period of time up to 8 years. SAH was initially diagnosed by brain computed tomography (CT). CT angiography (CTA) or digital subtraction angiography (DSA) was followed and SAH was confirmed to be due to cerebral aneurysm rupture. For cases when multiple bleeding occurred, the age of the first SAH was used in this study. The total incidence from all hospitals at each age group were summed together for females and males respectively; then adjusted by the total population number at each age group for females and males which was from the 2010 population census of the People's Republic of China.In total there were 8,144 cases of intracranial aneurysmal SAH, with 4,861 females and 3,283 males. For females the relative aneurysmal SAH incidence rate started to decrease after around 65 years old, while for males the relative aneurysmal SAH incidence rate started to decrease after around 53 years old.Our data tentatively suggest elderly patients may be at a reduced risk of rupture compared with patients who are younger while have similar other risk factors.

To investigate the effect of minimally invasive mini-incision and instrumented reduction combined with interlocking intramedullary nailing in the treatment of patients with multi-segment fracture of complex femoral shaft.From January 2013 to January 2016, 32 patients with multiple fractures segments of femoral shaft were treated with instrumentation-assisted reduction combined with interlocking intramedullary nailing, including 22 males and 10 females with an average age of 45 years old ranging 17 to 68 years old. The time from injured to operation was 5 to 10 days with an average of 7 days. After admission, routine tibial tubercle or supracondylar bone traction was performed. The patient's general condition was evaluated, the operation time and intraoperative blood loss were recorded. According to Thorsen femoral fracture morphology evaluation criteria and Hohl knee function evaluation of postoperative efficacy, postoperative fracture healing, complications and postoperative recovery of limb function were observed.All patients were followed up for 6 to 24 months with an average of 12 months. The operative time ranged from 48 to 76 minutes with an average of 67 min. The intraoperative blood loss was 150 to 400 ml with an average of 220 ml. The surgical incisions all achieved grade A healing. The fractures reached the clinical standard of healing. The fracture healing time ranged from 4.2 to 10.8 months with an average of 5.7 months. There were no nonunion, incision infection and internal fixation fracture, failure and other complications. According to Thorsen femoral fracture morphology evaluation criteria, the result was excellent in 28 cases, good in 3 cases, fair in 1 case. According to Hohl knee function evaluation criteria, the result was excellent in 30 cases, good in 2 cases.Instrument-assisted reduction combined with interlocking intramedullary nail fixation is a safe and effective method for the treatment of complex femoral shaft fractures. It has advantages of small trauma, fixed fixation, quick recovery, early postoperative functional exercise.

Stroke is a leading cause of death and disability worldwide. Ischemic stroke is the dominant subtype of stroke and results from focal cerebral ischemia due to occlusion of major cerebral arteries. Thus, the restoration or improvement of reduced regional cerebral blood supply in a timely manner is very critical for improving stroke outcomes and post-stroke functional recovery. The recovery from ischemic stroke largely relies on appropriate restoration of blood flow via angiogenesis. Newly formed vessels would allow increased cerebral blood flow, thus increasing the amount of oxygen and nutrients delivered to affected brain tissue. Angiogenesis is strictly controlled by many key angiogenic factors in the central nervous system, and these molecules have been well-documented to play an important role in the development of angiogenesis in response to various pathological conditions. Promoting angiogenesis via various approaches that target angiogenic factors appears to be a useful treatment for experimental ischemic stroke. Most recently, microRNAs (miRs) have been identified as negative regulators of gene expression in a post-transcriptional manner. Accumulating studies have demonstrated that miRs are essential determinants of vascular endothelial cell biology/angiogenesis as well as contributors to stroke pathogenesis. In this review, we summarize the knowledge of stroke-associated angiogenic modulators, as well as the role and molecular mechanisms of stroke-associated miRs with a focus on angiogenesis-regulating miRs. Moreover, we further discuss their potential impact on miR-based therapeutics in stroke through targeting and enhancing post-ischemic angiogenesis.

Previous studies have focused on miRNA expression in brain gliomas. However, both the expression pattern of miRNAs in gliomas of different grades and various miRNAs involved in malignant progression of gliomas are poorly understood. In the present study, we used miRNA microarray-based screening to investigate the miRNA expression profile in gliomas, which was further verified by qRT-PCR in selected miRNAs. In total, we found 13 differentially expressed miRNAs between gliomas and their matched surrounding tissues. Among them, 12 miRNAs were upregulated and only one (miR-4489) was downregulated compared with the control. Furthermore, the lower expression level of miR-4489 was confirmed by qRT-PCR in 26 glioma samples. Our microarray result revealed 8, 9 and 15 aberrantly expressed miRNAs in gliomas of World Health Organization (WHO) grade II-IV, respectively. Gene Ontology (GO) and Pathway analysis indicated that target genes of the 13 miRNAs were significantly enriched in central nervous system- and tumor-related biological processes and signaling pathways. The dysregulated miRNAs identified in the present study contribute to the tumorigenesis and malignant progression of gliomas and may serve as useful markers for advanced glioma pathological grading and prognosis.

Recent studies suggest that in humans, DNA sequences responsible for protein coding regions comprise only 2% of the total genome. The rest of the transcripts result in RNA transcripts without protein-coding ability, including long noncoding RNAs (lncRNAs). Different from most members in the lncRNA family, the metastasis-associated lung adenocarcinoma transcript 1 (Malat1) is abundantly expressed and evolutionarily conserved throughout various mammalian species. Malat1 is one of the first identified lncRNAs associated with human disease, and cumulative studies have indicated that Malat1 plays critical roles in the development and progression of various cancers. Malat1 is also actively involved in various physiologic processes, including alternative splicing, epigenetic modification of gene expression, synapse formation, and myogenesis. Furthermore, extensive evidences show that Malat1 plays pivotal roles in multiple pathological conditions as well. In this review, we will summarize latest findings related to the physiologic and pathophysiological processes of Malat1 and discuss its therapeutic potentials.

Cerebral vascular endothelial cells form the major element of the blood-brain barrier (BBB) and constitute the primary interface between circulating blood and brain parenchyma. The structural and functional changes in cerebral endothelium during cerebral ischemia are well known to result in BBB disruption, vascular inflammation, edema, and angiogenesis. These complex pathological processes directly contribute to brain infarction, neurological deficits, and post-stroke neurovascular remodeling. Ischemic endothelial dysfunction appears to be tightly controlled by multiple gene signaling networks. Non-coding RNAs (ncRNAs) are functional RNA molecules that are generally not translated into proteins but can actively regulate the expression and function of many thousands of protein-coding genes by different mechanisms. Various classes of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), small nucleolar RNAs (snoRNAs) and piwi-interacting RNAs (piRNAs), are highly expressed in the cerebrovascular endothelium where they serve as critical mediators to maintain normal cerebral vascular functions. Dysregulation of ncRNA activities has been closely linked to the pathophysiology of cerebral vascular endothelium and neurologic functional disorders in the brain’s response to ischemic stimuli. In this review, we summarize recent advancements of these ncRNA mediators in the brain vasculature, highlighting the specific roles of endothelial miRNAs in stroke.

Transcription factors play an important role in the pathophysiology of many neurological disorders, including stroke. In the past three decades, an increasing number of transcription factors and their related gene signaling networks have been identified, and have become a research focus in the stroke field. Krüppel-like factors (KLFs) are members of the zinc finger family of transcription factors with diverse regulatory functions in cell growth, differentiation, proliferation, migration, apoptosis, metabolism, and inflammation. KLFs are also abundantly expressed in the brain where they serve as critical regulators of neuronal development and regeneration to maintain normal brain function. Dysregulation of KLFs has been linked to various neurological disorders. Recently, there is emerging evidence that suggests KLFs have an important role in the pathogenesis of stroke and provide endogenous vaso- or neuro- protection in the brain’s response to ischemic stimuli. In this review, we summarize the basic knowledge and advancement of these transcriptional mediators in the central nervous system, highlighting the novel roles of KLFs in stroke.

Mantle cell lymphoma (MCL) remains incurable and new treatments are needed, especially in the relapsed/refractory setting. We therefore investigated the effects of carfilzomib, a novel, long-acting, second-generation proteasome inhibitor, in MCL cells. Eight established MCL cell lines and freshly isolated primary MCL cells were treated with carfilzomib. Cell proliferation was assessed by a 3H-thymidine incorporation assay. Cell apoptosis was evaluated by flow cytometry with annexin V and propidium iodide. Electrophoresis mobility shift (EMSA), Western blot, and luciferase assays were used to analyze NF-κB activation and related signaling proteins. Carfilzomib inhibited growth and induced apoptosis in both established MCL cell lines and freshly isolated primary MCL cells in a dose-dependent manner. In contrast, carfilzomib was less toxic to normal peripheral blood mononuclear cells from healthy individuals. The carfilzomib-induced apoptosis of MCL cells occurred in a caspase-dependent manner through both intrinsic and extrinsic caspase pathways. In addition, carfilzomib inhibited constitutive activation of the NF-κB signaling cascade, both in MCL cell lines and primary MCL cells, by completely blocking the phosphorylation of IκBα. Our results demonstrate that carfilzomib can induce growth arrest and apoptosis in MCL cells and that the mechanism may involve the NF-κB signaling pathway.

Sex differences between women and men are often overlooked and underappreciated when studying the cardiovascular system. It has been long assumed that men and women are physiologically similar, and this notion has resulted in women being clinically evaluated and treated for cardiovascular pathophysiological complications as men. Currently, there is increased recognition of fundamental sex differences in cardiovascular function, anatomy, cell signaling, and pathophysiology. The National Institutes of Health have enacted guidelines expressly to gain knowledge about ways the sexes differ in both normal function and diseases at the various research levels (molecular, cellular, tissue, and organ system). Greater understanding of these sex differences will be used to steer future directions in the biomedical sciences and translational and clinical research. This review describes sex-based differences in the physiology and pathophysiology of the vasculature, with a special emphasis on sex steroid receptor (estrogen and androgen receptor) signaling and their potential impact on vascular function in health and diseases (e.g., atherosclerosis, hypertension, peripheral artery disease, abdominal aortic aneurysms, cerebral aneurysms, and stroke).

Background and Purpose To investigate the clinical and morphological characteristics associated with risk factors for the rupture of bifurcation-type middle cerebral artery aneurysms (MCAAs). Methods A total of 169 consecutive patients with 177 bifurcation-type MCAAs were reviewed from August 2011 to January 2016. Based on the clinical and morphologic characteristics findings, the risk factors of aneurysm rupture were assessed using statistical methods. Results Age, cerebral atherosclerosis, no hypertension, hypertension grade 2 and coronary artery disease (CAD) were negatively correlated with aneurysm rupture. The mean diameter (MD) of the parent and two daughter arteries was negatively correlated with rupture. Aneurysms with irregularity, depth, width, maximum size, aspect ratio, depth-to-width ratio, bottleneck factor, and size ratio were positively correlated with rupture. The multivariate logistic regression model revealed that irregular shape (odds ratio (OR) 2.697) and aspect ratio (OR 3.723) were significantly and positively correlated with rupture, while cerebral atherosclerosis (OR 0.033), CAD (OR 0.080), and MD (OR 0.201) were negatively correlated with rupture. Receiver operating characteristic analysis revealed that the threshold value of the aspect ratio and MD were 0.96 and 2.43 mm, respectively. Conclusions Cerebral atherosclerosis and CAD are protective factors against rupture. Morphological characteristics such as an aneurysm with an irregular shape, a high aspect ratio (>0.96) and a small MD (

Burkitt lymphoma (BL) has been reported to be strongly associated with Epstein-Barr virus (EBV) infection. The fact that EBV is generally present in cancer cells but rarely found in healthy cells represents an opportunity for targeted cancer therapy. One approach is to activate the lytic replication cycle of the latent EBV. Nuclear factor (NF)-κB is thought to play an essential role in EBV lytic infection. Elevated NF-κB levels inhibit EBV lytic replication. Parthenolide (PN) is a sesquiterpene lactone found in medicinal plants, particularly in feverfew (Tanacetum parthenium). The aim of the present study was to analyze the effect of PN on the survival of Raji EBV-positive lymphoma cells. Raji cells were treated with 0, 4 or 6 µmol/l PN for 48 h. MTT assay and western blot analysis were performed to evaluate the findings. Results showd that PN suppressed the growth of the EBV-positive BL cell line, Raji, and activated the transcription of BZLF1 and BRLF1 by inhibiting NF-κB activity. Most notably, when PN was used in combination with ganciclovir (GCV), the cytotoxic effect of PN was amplified. These data suggest that the induction of lytic EBV infection with PN in combination with GCV may be a viral‑targeted therapy for EBV-associated BL.

Two ruthenium(II) complexes [Ru(bpy)(2)(bfipH)](2+) (1) and [Ru(phen)(2)(bfipH)](2+) (2) have been synthesized and characterized. The DNA-binding behaviors of complexes were studied by using spectroscopic and viscosity measurements. Results suggested that the two complexes bind to DNA in an intercalative mode. Complexes 1 and 2 can efficiently photocleave pBR322 DNA in vitro under irradiation, singlet oxygen ((1)O(2)) was proved to contribute to the DNA photocleavage process. Topoisomerase inhibition and DNA strand passage assay confirmed that two Ru(II) complexes acted as efficient dual inhibitors of topoisomerases I and II. In MTT cytotoxicity studies, two Ru(II) complexes exhibited antitumor activity against BEL-7402, HeLa, MCF-7 tumor cells. The AO/EB staining assay indicated that Ru(II) complexes could induce the apoptosis of HeLa cells.

It is recognized that expression of AQP4 protein is much greater in gliomas than in normal tissue. The relationship between AQP4 and glioma-associated brain edema is affected by osmotic pressure and hypoxia. In this study, we detected changes of AQP4 expression in tumor and peritumoral edematous tissues to analyze the relationship between AQP4 protein and the edema index (EI). We also detected expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor-1α (HIF-1α) to investigate their relationship with AQP4 protein, and thus to uncover the molecular biological mechanisms of AQP4 expression in glioma-associated brain edema. Sixty-five patients with brain glioma were divided into tumor and peritumor groups. Fresh tumor specimens, including six cases of grade I glioma, 18 of grade II, 11 of grade III and 30 of grade IV, and peritumoral edematous tissue specimens (1 cm distant from the tumor) were resected from these patients, and AQP4 protein expression levels were detected by western blot. Different AQP4 expression in the tumor and peritumor groups were compared. The relationship between AQP4 expression levels and the degree of peritumoral edema, and expression differences in different grades, were analyzed. Immunofluorescence cytochemistry was used to detect positive expression of AQP4 protein, VEGF protein, and HIF-1α protein in tumor tissue, and differences between expression were analyzed. Western blot showed that AQP4 expression in the peritumor (0.7697 ± 0.0941) and tumor (0.6934 ± 0.0625) groups was higher than in the control group (0.6215 ± 0.0884), and was highest in the peritumor group (both P0.01). AQP4 expression level in the peritumor group was positively correlated with EI (r = 0.677, P0.001) whereas AQP4 expression level in the tumor group was not correlated with EI (r = 0.096, P0.05). AQP4 expression increased with higher tumor grades in the peritumor group, but differences were not significant in the tumor group. Immunofluorescence cytochemical staining revealed that AQP4 protein in normal brain tissue was mainly expressed in the cell membrane surface, and that cytoplasm and nuclear staining was shallow. In glioma cells, AQP4 was widely distributed in the cytoplasm, particularly in the edematous area around the tumor. AQP4 protein expression in the tumor was significantly positively correlated with both VEGF protein (r = 0.877, P0.001) and HIF-1α protein (r = 0.876, P0.001). AQP4 expression was higher in brain tumor, especially peritumor. The degree of peritumoral edema correlates with AQP4 protein expression only in peritumor, whereas AQP4 expression is in accordance with expression of VEGF and HIF-1α. In glioma-associated brain edema, AQP4 is coregulated by osmotic pressure and hypoxia, with predominance of osmotic regulation, and is redistributed in glioma cells, mainly in the cytoplasm, and its expression level increased with higher glioma grades.