Long noncoding RNA SNHG14 promotes malignancy of prostate cancer by regulating with miR-5590-3p/YY1 axis.

OBJECTIVE: Studies have demonstrated that long non-coding RNAs (lncRNAs) are important in the development and prognosis of prostate cancer. The aim of this study was to investigate the functions and mechanism of lnc-SNHG14 in prostate cancer. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) or Western blot (WB) were performed to detect mRNA expressions of SNHG14 and miR-5590-3p, and the protein levels of Yin Yang-1 (YY1) in prostate cancer tissues, adjacent tissues, and cancer cell lines. The correlation analysis was used to analyze the correlations between SNHG14, miR-5590-3p, and YY1. Kaplan-Meier survival analysis was used to analyze the overall survival for prostate cancer patients. Cell Counting Kit-8 (CCK-8) assay was performed to measure cell proliferation ability and flow cytometry assay was used to detect cell apoptotic rate. Besides, transwell assay was used to measure cell invasion ability. In addition, WB was performed to measure protein expressions in prostate cancer cell lines. Finally, Luciferase reporter assay was performed to verify the binding sites between SNHG14 and miR-5590-3p, miR-5590-3p, and YY1. RESULTS: The results showed that SNHG14 was significantly increased in prostate cancer tissues and prostate cancer cell lines, which were related with advanced stage and poor diagnosis for prostate cancer patients. MiR-5590-3p was reduced in prostate cancer tissues and cell lines, which were negatively correlated with SNHG14. YY1 was found to be increased in prostate cancer tissues, which was negatively correlated with miR-5590-3p and positively correlated with SNHG14. Furthermore, SNHG14 knockdown inhibited cell proliferation, invasion, and promoted cell apoptosis in DU145 cells. In addition, protein expressions of Cyclin D1, Bcl-2, and N-cadherin were repressed, and the levels of Bax, Cleaved Caspase-3, and E-cadherin were increased. Besides, miR-5590-3p inhibition promoted cell proliferation and invasion, and inhibited apoptosis in DU145 cells. Importantly, Luciferase reporter assay proved that SNHG14 could directly sponge with miR-5590-3p, which could bind with YY1 and regulate the functions of cancer cell. Finally, we proved that SNHG14 regulated cell proliferation, cell apoptosis, and invasion via miR-5590-3p/ YY1 axis in prostate cancer. CONCLUSIONS: Above all, we found that SNHG14 was increased in prostate cancer patients, which was related with future diagnosis for prostate cancer patients. Of note, we discovered that SNHG14 could promote cell proliferation, invasion, and repress cell apoptosis via miR-5590-3p/YY1 axis in prostate cancer, which might provide a new target for treating prostate cancer.

[Clinical study of microvascular decompression in patients with coexistent hemifacial spasm and ipsilateral trigeminal neuralgia].

Objective: To investigate the surgical nuances and efficacy of microvascular decompression in patients with coexistent hemifacial spasm and ipsilateral trigeminal neuralgia. Methods: Seventeen patients suffered from coexistent hemifacial spasm and ipsilateral trigeminal neuralgia were treated in Department of Neurosurgery, Henan Provincial People's Hospital from January 2008 to September 2017. The medical recorders, intra-operative findings and postoperative follow-up results of these patients were reviewed, and the surgical strategies and therapeutic effects of these patients were summarized. Results: The offending vessels of the patients coexistent hemifacial spasm and ipsilateral trigeminal neuralgia were complex. The tortuous vertebral artery shifted to the suffered side in nine patients (52.9%), among which seven cases had vertebral artery as the offending vessel or indirect offending vessel compressing facial nerve and/or trigeminal nerve. The effective rate was 100%,the cure rate was 94.1%, and the immediate relief rate was 82.4%. All the patients were followed up for more than one year without recurrence. Conclusion: Patients with coexistent hemifacial spasm and ipsilateral trigeminal neuralgia with tortuous vertebral artery shifted to the affected side were more common. Good surgical nuances and strategies in microvascular decompression are the guarantee of successful surgery.

Factors predictive of outcome in patients with de novo status epilepticus.

BACKGROUND: About 50% of status epilepticus (SE) patients have no previous history of epilepsy, but often have worse outcome. The aim of this study was to evaluate potential risk factors that are predictive of poor outcome in non-selected de novo status epilepticus patients. METHODS: Eighty-three adult status epilepticus patients without a pre-existing history of epilepsy that were admitted to hospital for treatment were enrolled in this 11-year retrospective study. The baseline prognostic variables were analyzed based on stepwise logistic regression analysis after a minimum of one-and-half years of follow-up. RESULTS: The overall fatality rate was 55.4% (46/83) during the study period. Poor outcome was associated with older age, presence of refractory status epilepticus, potential fatal etiologies, lower GCS score at presentation and level of consciousness on admission. The results of stepwise logistic regression demonstrated that age on presentation and potential fatal etiologies were independently associated with presence of poor outcome, and any increase in age by 1 year increases poor outcome by 7.5%. CONCLUSION: The outcome for those with de novo status epilepticus is poor and this poor outcome may be attributed to the older age at onset and the potential fatal underlying conditions such as infection and metabolic derangement.

Stroke complicating pregnancy and the puerperium.

Stroke complicating pregnancy and the puerperium in Taiwan and the comparison between Western and Eastern countries have not been well studied. We identified retrospectively 32 cases of stroke from 66,781 deliveries, including 21 intracranial hemorrhages and 11 cerebral infarctions from 1992 to 2004. The most common causes of intracranial hemorrhage were vascular anomaly (29%), pre-eclampsia/eclampsia (24%), undetermined (24%) and coagulopathy (19%). The most common causes of cerebral infarction were cardioembolism (36%), cerebral venous thrombosis (27%) and pre-eclampsia/eclampsia (18%). Perinatal adverse outcome included two stillbirths, nine premature deliveries and four abortions. The compiled results of previous studies and ours revealed that intracranial hemorrhage appeared to be slightly more common in Taiwan (43-69%) than in the Western countries (33-52%). The average maternal mortality rate was 17.8% (range 9-38) with 77.8% due to intracranial hemorrhage. The average incidence of stroke associated with pregnancy and the puerperium was 21.3 per 100,000 deliveries (range 8.9-67.1). Our study, different from the Western countries, showed that intracranial hemorrhage is slightly more common than cerebral infarction. Pre-eclampsia/eclampsia is an important cause of stroke, however, the possibility of cardioembolism in cerebral infarction and vascular anomaly in intracranial hemorrhage should be studied.

Hypercalcemia and status epilepticus relates to salmon calcitonin administration in breast cancer.

Calcitonin is currently used to treat hypercalcemia of many clinical types. However, we encountered a woman who suffered severe hypercalcemia and status epilepticus, both of which developed 8 days after the administration of salmon calcitonin for the treatment of breast cancer. When the patient first presented her serum calcium level was 15.5mg/dl, intact parathyroid hormone level 118 pg/ml, calcitonin <2 pg/ml, magnesium 1.2mg/dl, and phosphate 1mg/dl. Her serum calcium level returned to the reference range within 48 h after correction. At follow-up no hypercalcemia had developed, although the patient had received no further treatment for her breast cancer and multiple metastases were subsequently detected. Her hypercalcemia is ascribed to exogenous calcitonin supplementation. These conflicting events may be due to functionally heterogeneous calcitonin receptors or to activation of 1 alpha-hydroxylase by exogenous calcitonin.

Spontaneous intracerebral hemorrhage in young adults.

Few studies have addressed intracerebral hemorrhage (ICH) in younger adults. We studied spontaneous ICH in adults

An improved method for determination of heavy metal bioavailability in contaminated soil.

Bioavailability of heavy metal in contaminated soil is investigated. A general diffusion model for determining the heavy metal bioavailability in soil has been developed The bioavailability predictions based on the present model were more accurate than those based on a previous model. Experimental results obtained using cadmium-, copper-, zinc- and lead-contaminated soils were employed for model verification. The effects of soil pH, initial heavy metal concentration, temperature and soil type on the effective diffusion coefficient or bioavailability index were also examined experimentally. The theoretical model and experimental procedure proposed in the present study provide a convenient means for the determination of heavy metal or inorganic ion bioavailability in contaminated soil.

Combination versus alternating chemotherapy in small-cell lung cancer.

BACKGROUND: The major obstacles in the treatment of small-cell lung cancer (SCLC) are tumor recurrence and the emergence of drug resistance to chemotherapeutic agents. Using alternating non-cross-resistant combination regimens is an attractive strategy, but the efficacy and toxicities are still controversial. METHODS: Previously untreated SCLC patients were randomly assigned to standard CEOV therapy (cyclophosphamide, epirubicin, vincristine = oncovin, and etoposide = VP-16) or CEOV alternating with CAM therapy (cyclophosphamide, ACNU and methotrexate). Chemotherapy was repeated every 4 weeks for a total of eight cycles. Complete and partial responders were administered thoracic irradiation. RESULTS: Between July 1987 and July 1993, 150 patients were enrolled and 123 were evaluable. There was no significant superiority in the treatment outcome for CEOV-CAM therapy over CEOV therapy in terms of overall response rate (51% vs 71%), complete response rate (9% vs 35%), median survival time (9.5 months vs 12.0 months) and 2-year survival rate (7% vs 13%). Both patients with limited disease and extensive disease had equal response rates to the CEOV regimen (70% and 71%, respectively). However, patients with limited disease had a significantly higher response rate to the CEOV-CAM regimen than did patients with extensive disease (65% vs 36%, p = 0.04). Toxicities for both treatment arms were comparable. Patients who achieved complete or partial response received thoracic irradiation and had significantly longer survival than responders who did not receive thoracic irradiation (14.0 months vs 12.0 months, p = 0.02). There were equal chances of tumor recurrence in the chest and at distant sites (66% vs 67%) in the CEOV arm. However, in the CEOV-CAM arm, tumors were more likely to occur in the chest than in distant sites (86% vs 36%) (p = 0.0016). CONCLUSIONS: We concluded that alternating chemotherapy provides no therapeutic advantage compared with four-regimen combination chemotherapy in terms of tumor response, median survival and 2-year survival rate for SCLC patients. Early thoracic irradiation should be applied to achieve better local control and less distant recurrence for chemotherapy responders.

Removal of heavy metals from aqueous solution by chelating resin in a multistage adsorption process.

Copper and zinc removal from aqueous solution by chelating resin was investigated theoretically and experimentally in the present study. A multistage process was proposed as an alternative for enhancement of the heavy removal of the single-stage process. Heavy metal mass balance equations with empirical Freundlich adsorption isotherm were developed to represent the multistage process and the theoretical model permits determination of the inter-stage heavy metal concentrations and the total amount of chelating resin required for achieving a desired level of heavy metal removal. Optimization of the linearized theoretical model shows that equal division of the total amount of chelating resin among all stages of the multistage process yields the best results in terms of saving of chelating resin for a given heavy metal removal or enhanced heavy metal removal for a given total amount of chelating resin. Experimental tests were also conducted to establish the equilibrium adsorption of heavy metal by the chelating resin and to empirically verify the advantages of the multistage adsorption process.

p53 gene status modulates the chemosensitivity of non-small cell lung cancer cells.

This study examined the effects of p53 gene status on DNA damage-induced cell death and chemosensitivity to various chemotherapeutic agents in non-small cell lung cancer (NSCLC) cells. A mutant p53 gene was introduced into cells carrying the wild-type p53 gene and also vice versa to introduce the wild-type p53 gene into cells carrying the mutant p53 gene. Chemosensitivity and DNA damage-induced apoptosis in these cells were then examined. This study included five cell lines, NCI-H1437, NCI-H727, NCI-H441 and NCI-H1299 which carry a mutant p53 gene and NCI-H460 which carries a wild-type p53 gene. Mutant p53-carrying cells were transfected with the wild-type p53 gene, while mutant p53 genes were introduced into NCI-H460 cells. These p53 genes were individually mutated at amino acid residues 143, 175, 248 and 273. The representative cell line NCI-H1437 cells transfected with wild-type p53 gene (H1437/wtp53) showed a dramatic increase in susceptibility to three anticancer agents (7-fold to cisplatin, 21-fold to etoposide, and 20-fold to camptothecin) compared to untransfected or neotransfected H1437 cells. An increase in chemosensitivity was also observed in wild-type p53 transfectants of H727, H441, H1299 cells. The results of chemosensitivity were consistent with the observations on apoptotic cell death. H1437/wtp53 cells, but not H1437 parental cells, exhibited a characteristic feature of apoptotic cell death that generated oligonucleosomal-sized DNA fragments. In contrast, loss of chemosensitivity and lack of p53-mediated DNA degradation in response to anticancer agents were observed in H460 cells transfected with mutant p53. These observations suggest that the increase in chemosensitivity was attributable to wild-type p53 mediation of the process of apoptosis. In addition, our results also suggest that p53 gene status modulates the extent of chemosensitivity and the induction of apoptosis by different anticancer agents in NSCLC cells.

Interprotein disulfide bonds formed during isolation process tighten the structure of the postsynaptic density.

Postsynaptic densities (PSDs) isolated by biochemical means consist of a complex mixture of proteins that tightly bond to each other. The purpose of this report is to study whether the numerous interprotein disulfides found in the isolated PSDs contribute to the tight structure of the PSDs and whether these interprotein disulfides exist in vivo. PSDs were isolated from pig cerebral cortex by conventional methods except that iodoacetic acid (IAA) was added to all solutions to curtail the formation of disulfides during the isolation process. The PSDs thus isolated were fragmented easily by treatment with chaotropic reagents or ionic detergents, whereas the PSDs isolated in IAA-free solutions were resistant to these treatments. Electron microscopy revealed that the PSDs isolated in IAA-containing solutions were more fragmented than those isolated in IAA-free solutions. Furthermore, the PSD sample isolated in IAA-free solutions contained very large disulfide-linked aggregates that were virtually absent from the PSDs isolated in IAA-containing solutions. Our results suggest that the exceptionally tight structure of the PSDs isolated by conventional methods is due largely to the new disulfides formed during the isolation process and that the PSD proteins under in vivo conditions are held together primarily by noncovalent interactions.

Stroke survival after discharge from an acute-care hospital.

BACKGROUND AND PURPOSE: Survival after a stroke is likely to be best for patients well enough to be sent home but the relative risk of dying if patients do not qualify for a home discharge has not been well studied. We investigated the survival prognosis after an initial stroke depending on the facility to which the patient was discharged after an acute initial stroke. METHODS: All patients were enrolled between July 1, 1987, and August 1, 1989, and were followed up to 4 years (mean of 24 months) until death, second stroke, or the end of the study. RESULTS: Among 662 patients who were discharged alive after hospitalization with an initial stroke, 128 (19%) went to a nursing home, 17(3%) to a short-term hospital, 140 (21%) to a rehabilitation facility, and 375 (57%) went home (discharge destination unknown for 2 patients). Compared to patients sent home after taking age, sex, selected baseline comorbidities, length of hospital stay, and neurological deficits into consideration, results from Cox proportional hazards model indicated that patients sent to a nursing home had 2.6 times greater risk of dying (95% CI = 1.81-4. 15) while those who were discharged to a rehabilitation facility had a death hazards ratio of 1.1. CONCLUSIONS: Mortality was greatest in the early months after discharge and decreased thereafter. Since the analysis was adjusted for age, sex, comorbidity, length of hospital stay, and number of neurological deficits, quality of care in a nursing home setting may account for the mortality difference but other factors such as social support network and living will instructions also need to be investigated.

The efficacy of CNES-2 in detecting the neurobehavioral changes of epileptic patients.

The Neurobehavioral Evaluation System (NES) and the Chinese Neurobehavioral Evaluation System-2 (CNES-2) have been widely used to detect central nervous dysfunction associated with exposure to a variety of neurotoxicants. The NES has recently been validated as a measure of central nervous system (CNS) dysfunction in patients with well-characterized neurological disorders such as Parkinson disease and multiple sclerosis. Validation of the NES was also been done through correlation study with traditional neuropsychological tests. The purpose of present study was to assess the efficacy of CNES-2 in detecting the neurobehavioral change of the epileptic patients, another neurological disorders that can have associated subtle neurobehavioral changes. Furthermore, seizures sometimes occur following exposure to neurotoxicants. Results showed the performance on many subtests of CNES-2 was impaired in the epileptic patients compared to the controls. Our conclusion is that the CNES-2 is a worthwhile tool for identifying subtle neurobehavioral abnormalities.

Characterization of the human endothelial nitric-oxide synthase promoter.

Understanding transcription initiation of the endothelial nitric-oxide synthase (eNOS) gene appears pivotal to gaining a comprehensive view of NO biology in the blood vessel wall. The present study therefore focused upon a detailed dissection of the functionally important cis-DNA elements and the multiprotein complexes implicated in the cooperative control of constitutive expression of the human eNOS gene in vascular endothelium. Two tightly clustered cis-regulatory regions were identified in the proximal enhancer of the TATA-less eNOS promoter using deletion analysis and linker-scanning mutagenesis: positive regulatory domains I (-104/-95 relative to transcription initiation) and II (-144/-115). Analysis of trans-factor binding and functional expression studies revealed a surprising degree of cooperativity and complexity. The nucleoprotein complexes that form upon these regions in endothelial cells contained Ets family members, Sp1, variants of Sp3, MAZ, and YY1. Functional domain studies in Drosophila Schneider cells and endothelial cells revealed examples of positive and negative protein-protein cooperativity involving Sp1, variants of Sp3, Ets-1, Elf-1, and MAZ. Therefore, multiprotein complexes are formed on the activator recognition sites within this 50-base pair region of the human eNOS promoter in vascular endothelium.

Characterization of granular particles isolated from postsynaptic densities.

We describe here the isolation and biochemical characterization of a population of protein aggregates from the postsynaptic density (PSD) prepared from pig cerebral cortex. The protein constituents of these aggregates are linked together primarily by disulfide bonds. Negative staining electron microscopy revealed that the isolated protein aggregates were granular objects with an average outside diameter of approximately 21 nm and with small protrusions on their surface. The major constituents of the isolated granular aggregates consist of tubulin and an unidentified protein of 70 kDa in size. Small amounts of the alpha subunit of calcium/calmodulin-dependent protein kinase II and subunits of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and NMDA subtypes of glutamate receptors were also detected by immunoblotting. Actin, however, was not found in these granular aggregates. We propose that these granular protein aggregates correspond to the approximately 20-nm-diameter granular particles of the PSD on the basis of their biochemical and morphological characteristics. The spatial arrangement of these granular aggregates relative to other components of the postsynaptic terminal is also postulated here.

Dynorphin uses a non-opioid mechanism to potentiate N-methyl-D-aspartate currents in single rat periaqueductal gray neurons.

The interaction of the endogenous K-opioid, dynorphin, with N-methyl-D-aspartate (NMDA) receptors was studied in single periaqueductal gray (PAG) cells using the whole cell patch recording technique. We have found that dynorphin A (1-17) rapidly and reversibly potentiates NMDA-activated currents in a subpopulation of PAG cells. The potentiation cannot be blocked by the non-specific opioid antagonist, naloxone, nor can it be reversed by the specific kappa-opioid antagonist, nor-BNI. In addition, the non-opioid fragment of dynorphin, dynorphin A (2-17), is effective in potentiating NMDA currents, while the specific kappa-opioid, U50,488, cannot mimic the action of dynorphin A (1-17). The non-opioid dynorphin action and the rapid onset and recovery of the potentiation are consistent with the idea that dynorphin interacts directly with NMDA receptors in PAG cells.

Impact of nutritional status on the survival of lung cancer patients.

BACKGROUND: Weight loss, disease extent, performance status and sex have emerged as prognostic factors for lung cancer. The assessment of performance status is rather subjective and crude. Parameters of nutritional status were used in this study to represent the performance status of patients. The prevalence of protein-calorie malnutrition in lung cancer patients and the impact of this on patient survival were also investigated. METHODS: Nutritional status was assessed in 150 newly diagnosed lung cancer patients. Anthropometric and biochemical parameters measured were: weight/height ratio, percent of standard triceps skin-fold thickness, percent of standard arm muscle circumference, serum albumin, transferrin, creatinine height index and total lymphocyte count. Performance status and survival time were estimated for all patients. RESULTS: The prevalence of abnormality in each nutritional parameter ranged from 15 to 31%. Most of the patients (59%) had at least one abnormal nutritional parameter. A low profile of performance status was associated with lower nutritional parameters such as triceps skin-fold thickness, percent of standard arm muscle circumference, serum albumin and creatinine height index. Patients who died within six months after diagnosis had significantly lower values of all nutritional parameters than those who survived more than six months. Patients with more abnormal parameters tended to have poorer survival rates. CONCLUSIONS: Both anthropometric and biochemical nutritional parameters might be reliable indicators for the assessment of performance status and survival for patients with lung cancer.