Solar-activated and hydrothermally synthesized effective rGO/Ag2S composites for the destruction of naphthol green B dye and antibacterial applications.

Graphene-based nanocomposites are developing as a new class of materials with several uses. The varied weight percentages of rGO on Ag2S catalysts were synthesized using a simple hydrothermal process and employed for the decomposition of anionic dye naphthol green B (NGB) under solar light. The reduced graphene oxide-based silver sulfide (rGO/Ag2S) nanoparticles were then examined using XRD, SEM, EDS, HR-TEM, XPS, UV-DRS, and PL analysis. Using solar light, the photocatalytic activity of the produced catalyst was examined for the degradation of naphthol green B (NGB) in an aqueous solution. At pH 9, rGO/Ag2S is discovered to be more effective than the other catalysts for the NGB dye mineralization. Analyses have been conducted on the influence of operational parameters on the photo-mineralization of NGB, including the initial pH, initial dye concentration, and catalyst dosage. The dye concentration increased; the efficiency of photocatalytic degradation tended to decrease. Chemical oxygen demand (COD) studies have verified the NGB dye mineralization. Active species trapping revealed that holes, hydroxyl radicals, and superoxide radicals all played major roles in the photocatalytic deterioration of NGB processes. Additionally, a potential mechanism of NGB dye degradation by rGO/Ag2S catalyst is presented. The synthesized compound was further evaluated for antibacterial activity, and the results indicated that rGO/Ag2S were potentially effective antibacterial agents.

Prognostic Values Serum Cav-1 and NGB Levels in Early Neurological Deterioration After Intravenous Thrombolysis in Patients with Acute Ischemic Stroke.

Early neurological deterioration after intravenous thrombolysis (IAT) leads to increased mortality and morbidity in patients with acute ischemic stroke (AIS). This study investigated the correlation between serum Cav-1 and NGB levels and END after IAT and explored their predictive values for poor prognosis of AIS. Totally 210 patients with AIS who underwent IAT within 4.5 h of onset were included and assigned into END group (n = 90) and Non-END group (n = 120). ELISA was used to detect serum Cav-1 and NGB levels before IAT in AIS patients. The prognosis of END patients after 3 months of treatment was evaluated using the modified Rankin Scale. Logistic multifactorial regression was used to analyze independent risk factors for END and poor prognosis after IAT. ROC curve was used to analyze the predictive effect of Cav-1 and NGB on END and poor prognosis after IAT. The area under the ROC curve was analyzed by MedCalc comparison. Compared with the Non-END group, serum Cav-1 was lower and NGB was higher in the END group. Cav-1 and NGB were independent risk factors for END after IAT. Cav-1 + NGB better predicted END after IAT than Cav-1 or NGB alone. Cav-1 and NGB were independent risk factors for END poor prognosis after IAT. Cav-1 combined with NGB better predicted poor prognosis of END after IAT than Cav-1 or NGB alone. Serum Cav-1 combined with NGB may assist in predicting the risk of END occurrence and poor prognosis after IAT in patients with AIS.

Neuroglobin plays as tumor suppressor by disrupting the stability of GPR35 in colorectal cancer.

BACKGROUND: The incidence of colorectal cancer (CRC) has increased in recent years. Identification of accurate tumor markers has become the focus of CRC research. Early and frequent DNA methylation tends to occur in cancer. Thus, identifying accurate methylation biomarkers would improve the efficacy of CRC treatment. Neuroglobin (NGB) is involved in neurological and oncological diseases. However, there are currently no reports on epigenetic regulation involvement of NGB in CRC. RESULTS: NGB was downregulated or silenced in majority CRC tissues and cell lines. The hypermethylation of NGB was detected in tumor tissue, but no or a very low methylation frequency in normal tissues. Overexpression of NGB induced G2/M phase arrest and apoptosis, suppressed proliferation, migration, invasion in vitro, and inhibited CRC tumor growth and angiogenesis in vivo. Isobaric tag for relative and absolute quantitation (Itraq)-based proteomics identified approximately 40% proteins related to cell-cell adhesion, invasion, and tumor vessel formation in the tumor microenvironment, among which GPR35 was proved critical for NGB-regulated tumor angiogenesis suppression in CRC. CONCLUSIONS: NGB, an epigenetically silenced factor, inhibits metastasis through the GPR35 in CRC. It is expected to grow into a potential cancer risk assessment factor and a valuable biomarker for early diagnosis and prognosis assessment of CRC.

Neural and molecular investigation into the paraventricular thalamic-nucleus accumbens circuit for pain sensation and non-opioid analgesia.

The paucity of medications with novel mechanisms for pain treatment combined with the severe adverse effects of opioid analgesics has led to an imperative pursuit of non-opioid analgesia and a better understanding of pain mechanisms. Here, we identify the putative glutamatergic inputs from the paraventricular thalamic nucleus to the nucleus accumbens (PVTGlut→NAc) as a novel neural circuit for pain sensation and non-opioid analgesia. Our in vivo fiber photometry and in vitro electrophysiology experiments found that PVTGlut→NAc neuronal activity increased in response to acute thermal/mechanical stimuli and persistent inflammatory pain. Direct optogenetic activation of these neurons in the PVT or their terminals in the NAc induced pain-like behaviors. Conversely, inhibition of PVTGlut→NAc neurons or their NAc terminals exhibited a potent analgesic effect in both naïve and pathological pain mice, which could not be prevented by pretreatment of naloxone, an opioid receptor antagonist. Anterograde trans-synaptic optogenetic experiments consistently demonstrated that the PVTGlut→NAc circuit bi-directionally modulates pain behaviors. Furthermore, circuit-specific molecular profiling and pharmacological studies revealed dopamine receptor 3 as a candidate target for pain modulation and non-opioid analgesic development. Taken together, these findings provide a previously unknown neural circuit for pain sensation and non-opioid analgesia and a valuable molecular target for developing future safer medication.

Phenotyping of light-activated neurons in the mouse SCN based on the expression of FOS and EGR1.

Light-sensitive neurons are located in the ventral and central core of the suprachiasmatic nucleus (SCN), whereas stably oscillating clock neurons are found mainly in the dorsal shell. Signals between the SCN core and shell are believed to play an important role in light entrainment. Core neurons express vasoactive intestinal polypeptide (VIP), gastrin-releasing peptide (GRP), and Neuroglobin (Ngb), whereas the shell neurons express vasopressin (AVP), prokineticin 2, and the VIP type 2 (VPAC2) receptor. In rodents, light has a phase-shifting capacity at night, which induces rapid and transient expression of the EGR1 and FOS in the SCN. Methods: The present study used immunohistochemical staining of FOS, EGR1, and phenotypical markers of SCN neurons (VIP, AVP, Ngb) to identify subtypes/populations of light-responsive neurons at early night. Results: Double immunohistochemistry and cell counting were used to evaluate the number of SCN neurons expressing FOS and EGR1 in the SCN. The number of neurons expressing either EGR1 or FOS was higher than the total number of neurons co-storing EGR1 and FOS. Of the total number of light-responsive cells, 42% expressed only EGR1, 43% expressed only FOS, and 15% expressed both EGR1 and FOS. Light-responsive VIP neurons represented only 31% of all VIP neurons, and EGR1 represents the largest group of light-responsive VIP neurons (18%). VIP neurons expressing only FOS represented 1% of the total light-responsive VIP neurons. 81% of the Ngb neurons in the mouse SCN were light-responsive, and of these neurons expressing only EGR1 after light stimulation represented 44%, whereas 24% expressed FOS. Although most light-responsive neurons are found in the core of the SCN, 29% of the AVP neurons in the shell were light-responsive, of which 8% expressed EGR1, 10% expressed FOS, and 11% co-expressed both EGR1 and FOS after light stimulation. Discussion: Our analysis revealed cell-specific differences in light responsiveness between different peptidergic and Ngb-expressing neurons in different compartments of the mouse SCN, indicating that light activates diverse neuronal networks in the SCN, some of which participate in photoentrainment.

Comparative study on the distribution and expression of Neuroglobin and Hypoxia-inducible factor-1α in the telencephalon of yak and cattle / Estudo comparativo da distribuição e expressão de fator-1α indutível por neuroglobina e hipóxia no telencéfalo de iaques e bovinos

The telencephalon refers to the most highly developed and anterior part of the forebrain, consisting mainly of the cerebral hemispheres. The study determined Neuroglobin (Ngb) and Hypoxia-inducible factor (HIF-1α) expression in the telencephalon of yak and cattle, and compare the expression and distribution pattern of Ngb and HIF-1α in the two animals. Immunohistochemistry (IHC), quantitative real-time Polymerase Chain Reaction (qRT-PCR), and Western blot (WB) were employed to investigate Ngb and Hif-1α expression in the telencephalon of yak and cattle. mRNA and protein expressions of Ngb and HIF-1α showed positive in different tissues of the yak and cattle telencephalon. Ngb expression in tissues of the yak recorded higher as compare to cattle while HIF-1α expression was found higher in cattle than yak. The HIF-1α expression in some tissues of yak telencephalon was consistent with the cattle. The results documented that HIF-1α may have a direct or indirect synergistic effect on Ngb expression in the yak telencephalon to improve hypoxia adaptation. It is suggested that yak may need more Ngb expression for adaptation, but the expression of HIF-1α seems to be down-regulated during long-term adaptation, and the specific causes of this phenomenon needs to be further verified.

O telencéfalo refere-se à parte anterior e mais desenvolvida do prosencéfalo, consistindo principalmente dos hemisférios cerebrais. O estudo determinou a expressão de neuroglobina (Ngb) e fator indutível por hipóxia (HIF-1α) no telencéfalo de iaques e bovinos e comparou a expressão e o padrão de distribuição de Ngb e HIF-1α nos dois animais. Imuno-histoquímica (IHC), reação em cadeia da polimerase quantitativa em tempo real (qRT-PCR) e Western blot (WB) foram empregados para investigar a expressão de Ngb e Hif-1α no telencéfalo de iaques e bovinos. As expressões de mRNA e proteínas de Ngb e HIF-1α mostraram-se positivas em diferentes tecidos do telencéfalo de iaque e bovino. A expressão de Ngb nos tecidos do iaque foi registrada mais alta em comparação com o gado, enquanto a expressão do HIF-1α foi encontrada mais alta no gado do que no iaque. A expressão de HIF-1α em alguns tecidos do telencéfalo de iaque foi consistente com o gado. Os resultados documentaram que o HIF-1α pode ter um efeito sinérgico direto ou indireto na expressão de Ngb no telencéfalo de iaque para melhorar a adaptação à hipóxia. É sugerido que o iaque pode precisar de mais expressão de Ngb para adaptação, mas a expressão de HIF-1α parece ser regulada para baixo durante a adaptação de longo prazo, e as causas específicas desse fenômeno precisam ser verificadas.

Comparative study on the distribution and expression of Neuroglobin and Hypoxia-inducible factor-1 in the telencephalon of yak and cattle

Abstract The telencephalon refers to the most highly developed and anterior part of the forebrain, consisting mainly of the cerebral hemispheres. The study determined Neuroglobin (Ngb) and Hypoxia-inducible factor (HIF-1) expression in the telencephalon of yak and cattle, and compare the expression and distribution pattern of Ngb and HIF-1 in the two animals. Immunohistochemistry (IHC), quantitative real-time Polymerase Chain Reaction (qRT-PCR), and Western blot (WB) were employed to investigate Ngb and Hif-1 expression in the telencephalon of yak and cattle. mRNA and protein expressions of Ngb and HIF-1 showed positive in different tissues of the yak and cattle telencephalon. Ngb expression in tissues of the yak recorded higher as compare to cattle while HIF-1 expression was found higher in cattle than yak. The HIF-1 expression in some tissues of yak telencephalon was consistent with the cattle. The results documented that HIF-1 may have a direct or indirect synergistic effect on Ngb expression in the yak telencephalon to improve hypoxia adaptation. It is suggested that yak may need more Ngb expression for adaptation, but the expression of HIF-1 seems to be down-regulated during long-term adaptation, and the specific causes of this phenomenon needs to be further verified.

Resumo O telencéfalo refere-se à parte anterior e mais desenvolvida do prosencéfalo, consistindo principalmente dos hemisférios cerebrais. O estudo determinou a expressão de neuroglobina (Ngb) e fator indutível por hipóxia (HIF-1) no telencéfalo de iaques e bovinos e comparou a expressão e o padrão de distribuição de Ngb e HIF-1 nos dois animais. Imuno-histoquímica (IHC), reação em cadeia da polimerase quantitativa em tempo real (qRT-PCR) e Western blot (WB) foram empregados para investigar a expressão de Ngb e Hif-1 no telencéfalo de iaques e bovinos. As expressões de mRNA e proteínas de Ngb e HIF-1 mostraram-se positivas em diferentes tecidos do telencéfalo de iaque e bovino. A expressão de Ngb nos tecidos do iaque foi registrada mais alta em comparação com o gado, enquanto a expressão do HIF-1 foi encontrada mais alta no gado do que no iaque. A expressão de HIF-1 em alguns tecidos do telencéfalo de iaque foi consistente com o gado. Os resultados documentaram que o HIF-1 pode ter um efeito sinérgico direto ou indireto na expressão de Ngb no telencéfalo de iaque para melhorar a adaptação à hipóxia. É sugerido que o iaque pode precisar de mais expressão de Ngb para adaptação, mas a expressão de HIF-1 parece ser regulada para baixo durante a adaptação de longo prazo, e as causas específicas desse fenômeno precisam ser verificadas.

Comparative study on the distribution and expression of Neuroglobin and Hypoxia-inducible factor-1α in the telencephalon of yak and cattle / Estudo comparativo da distribuição e expressão de fator-1 indutível por neuroglobina e hipóxia no telencéfalo de iaques e bovinos

Abstract The telencephalon refers to the most highly developed and anterior part of the forebrain, consisting mainly of the cerebral hemispheres. The study determined Neuroglobin (Ngb) and Hypoxia-inducible factor (HIF-1α) expression in the telencephalon of yak and cattle, and compare the expression and distribution pattern of Ngb and HIF-1α in the two animals. Immunohistochemistry (IHC), quantitative real-time Polymerase Chain Reaction (qRT-PCR), and Western blot (WB) were employed to investigate Ngb and Hif-1α expression in the telencephalon of yak and cattle. mRNA and protein expressions of Ngb and HIF-1α showed positive in different tissues of the yak and cattle telencephalon. Ngb expression in tissues of the yak recorded higher as compare to cattle while HIF-1α expression was found higher in cattle than yak. The HIF-1α expression in some tissues of yak telencephalon was consistent with the cattle. The results documented that HIF-1α may have a direct or indirect synergistic effect on Ngb expression in the yak telencephalon to improve hypoxia adaptation. It is suggested that yak may need more Ngb expression for adaptation, but the expression of HIF-1α seems to be down-regulated during long-term adaptation, and the specific causes of this phenomenon needs to be further verified.

Resumo O telencéfalo refere-se à parte anterior e mais desenvolvida do prosencéfalo, consistindo principalmente dos hemisférios cerebrais. O estudo determinou a expressão de neuroglobina (Ngb) e fator indutível por hipóxia (HIF-1α) no telencéfalo de iaques e bovinos e comparou a expressão e o padrão de distribuição de Ngb e HIF-1α nos dois animais. Imuno-histoquímica (IHC), reação em cadeia da polimerase quantitativa em tempo real (qRT-PCR) e Western blot (WB) foram empregados para investigar a expressão de Ngb e Hif-1α no telencéfalo de iaques e bovinos. As expressões de mRNA e proteínas de Ngb e HIF-1α mostraram-se positivas em diferentes tecidos do telencéfalo de iaque e bovino. A expressão de Ngb nos tecidos do iaque foi registrada mais alta em comparação com o gado, enquanto a expressão do HIF-1α foi encontrada mais alta no gado do que no iaque. A expressão de HIF-1α em alguns tecidos do telencéfalo de iaque foi consistente com o gado. Os resultados documentaram que o HIF-1α pode ter um efeito sinérgico direto ou indireto na expressão de Ngb no telencéfalo de iaque para melhorar a adaptação à hipóxia. É sugerido que o iaque pode precisar de mais expressão de Ngb para adaptação, mas a expressão de HIF-1α parece ser regulada para baixo durante a adaptação de longo prazo, e as causas específicas desse fenômeno precisam ser verificadas.

Mixed Micellar Solubilization of Naphthol Green B Followed by Its Removal from Synthetic Effluent by Micellar-Enhanced Ultrafiltration under Optimized Conditions.

In this manuscript, the application of cetyltrimethylammonium bromide (CTAB) and cetylpyridinium chloride (CPC) for the removal of Naphthol Green B (NGB) as a synthetic effluent has been studied. The solubilization of NGB by a single and mixed micellar system using Triton X-100 (TX-100) as a nonionic surfactant has been performed to establish both the extent of the partitioning (kx) of NGB and ultimately their respective Gibbs free energies ΔGp as well. An applied methodology, micellar-enhanced ultrafiltration (MEUF), has also been studied in different micellar media of cationic surfactants by variation in some selective parameters, such as the concentration of surfactant, electrolyte, pressure, pH, and RPM to obtain optimum conditions. The results have been analyzed by a UV/visible double beam spectrophotometer. ΔGp was found to be -39.65 kJ/mol and -47.94 kJ/mol by CTAB and CPC, respectively, in the presence of a nonionic surfactant. The maximum value of Gibbs free energy (ΔGp) of the partition was obtained by CPC. The values of the rejection coefficient (R%) and permeate flux (J) are also calculated. A maximum removal of 99.77% and 98.53% by CTAB and CPC, respectively, was obtained. It has been observed that both of the surfactants are strong candidates for NGB removal.

Expression and distribution of neuroglobin and hypoxia-inducible factor-1α in the adult yak telencephalon.

The telencephalon is also known as the cerebrum, and it consists of the largest part of the brain. It makes up about 85% of the total weight of the brain. Neuroglobin (Ngb) is a protein found in neurons of both the peripheral and central nervous system that appears to convey some resilience to hypoxia, while the hypoxia-inducible factor (Hif-1α) is a dimeric protein complex that plays an integral role in the body's response to low oxygen concentrations, or hypoxia. The study examines the expression of Ngb and Hif-1α in the telencephalon of adult yak in the telencephalon. The immunohistochemistry (IHC), quantitative real-time PCR and Western blot (WB) were employed to investigate Ngb and Hif-1α expression in the telencephalon. Ngb and Hif-1α are significantly expressed in all tissues of the telencephalon except the hypothalamus. The cerebellar cortex, hippocampus, amygdala, cerebellum and corpus callosum recorded the highest expression but not significant. The overall expression revealed that Ngb expression was higher as compared to Hif-1α. The IHC results also showed that the expression of Ngb and Hif-1α were higher in the cerebellar cortex, hippocampus, amygdala, cerebellum and corpus callosum as compared to other regions. The results suggested that Ngb and Hif-1α expression influence the adaptive mechanism of yak to the high altitude environment. Both Ngb and Hif-1α participate in oxygen transports throughout the telencephalon and have functions in neuroprotection. Further studies are needed to confirm the mechanism of adaptation.

Validity and reliability of Raman spectroscopy for carotenoid assessment in cattle skin.

Carotenoids are powerful antioxidants capable of helping to protect the skin from the damaging effects of exposure to sun by reducing the free radicals in skin produced by exposure to ultraviolet radiation, and they may also have a physical protective effect in human skin. Since carotenoids are lipophilic molecules which can be ingested with the diet, they can accumulate in significant quantities in the skin. Several studies on humans have been conducted to evaluate the protective function of carotenoids against various diseases, but there is very limited published information available to understand the mechanism of carotenoid bioavailability in animals. The current study was conducted to investigate the skin carotenoid level (SCL) in two cattle skin sets - weaners with an unknown feeding regime and New Generation Beef (NGB) cattle with monitored feed at three different ages. Rapid analytical and sensitive Raman spectroscopy has been shown to be of interest as a powerful technique for the detection of carotenoids in cattle skin due to the strong resonance enhancement with 532 nm laser excitation. The spectral difference of both types of skin were measured and quantified using univariate and linear discriminant analysis. SCL was higher in NGB cattle than weaners and there is a perfect classification accuracy between weaners and NGB cattle skin using carotenoid markers as a basis. Further work carried out on carotenoid rich NGB cattle skin of 8, 12 and 24 months of age identified an increasing trend in SCL with age. The present work validated the ability of Raman spectroscopy to determine the skin carotenoid level in cattle by comparing it with established HPLC methods. There is an excellent correlation of R2 = 0.96 between the two methods that could serve as a model for future application for larger population studies.

Prolonged dopamine D3 receptor stimulation promotes dopamine transporter ubiquitination and degradation through a PKC-dependent mechanism.

The dopamine transporter (DAT) is a membrane glycoprotein in dopaminergic neurons, which modulates extracellular and intracellular dopamine levels. DAT is regulated by different presynaptic proteins, including dopamine D2 (D2R) and D3 (D3R) receptors. While D2R signalling enhances DAT activity, some data suggest that D3R has a biphasic effect. However, despite the extensive therapeutic use of D2R/D3R agonists in neuropsychiatric disorders, this phenomenon has been little studied. In order to shed light on this issue, DAT activity, expression and posttranslational modifications were studied in mice and DAT-D3R-transfected HEK cells. Consistent with previous reports, acute treatment with D2R/D3R agonists promoted DAT recruitment to the plasma membrane and an increase in DA uptake. However, when the treatment was prolonged, DA uptake and total striatal DAT protein declined below basal levels. These effects were inhibited in mice by genetic and pharmacological inactivation of D3R, but not D2R, indicating that they are D3R-dependent. No changes were detected in mesostriatal tyrosine hydroxylase (TH) protein expression and midbrain TH and DAT mRNAs, suggesting that the dopaminergic system is intact and DAT is posttranslationally regulated. The use of immunoprecipitation and cell surface biotinylation revealed that DAT is phosphorylated at serine residues, ubiquitinated and released into late endosomes through a PKCß-dependent mechanism. In sum, the results indicate that long-term D3R activation promotes DAT down-regulation, an effect that may underlie neuroprotective and antidepressant actions described for some D2R/D3R agonists.

Electroacupuncture Inhibits Neuronal Apoptosis Induced by Bilirubin Encephalopathy in SD Suckling Rats by Regulating NGB and PI3K/Akt Signaling Pathways / 中国生物化学与分子生物学报

Objective In this study, electroacupuncture (EA) was used to analyze the expression changes of related proteins in neuroglobin (NGB), PI3K/AKT and apoptotic pathways in the temporal cortex of bilirubin encephalopathy (BE) rats, so as to investigate the therapeutic effect of EA on BE and the relevant mechanism of NGB in this process. Totally 39 seven-day-old SD rats were divided into Sham, BE model and BE+EA groups. The neonatal BE model was established by injecting bilirubin solution (10 μg UCB/g Weight) into the cerebellomedullary cistern, Sham group was injected with the same amount of normal saline. BE rats were treated with EA at Baihui (GV20) and Quchi (LI11) acupoints with the frequency of 2/15 Hz for 15 min. Treatment was performed 12 h before modeling, followed by treatment every 12 h, in a total of three times. HE, Nissl staining and electron microscopy (TEM) were used to observe the pathological and ultrastructural changes of nerve cells in each group. Results showed that EA treatment reduced the damage of cortical neurons of BE rats and increase the number of Nissl bodies. TEM confirmed that EA treatment could alleviate the degree of mitochondria edema. Immunofluorescence staining was used to detect the expression sites and cell types of NGB. Results showed that NGB was mainly expressed in cortical neurons. Western blotting showed that EA treatment increased the expression of NGB, PI3K (p110 alpha), pAKT (Ser473) (P< 0. 05, P< 0. 05 and P< 0. 01, respectively) and the ratio of apoptosis-related protein Bcl-2/Bax (P < 0. 001), decreased the expression of Cleaved Caspase-3 (P< 0. 05) in the temporal cortex of rats. TUNEL staining showed that EA reduced the number of apoptotic cells (BE group 186. 00±13. 86 vs BE+EA group 78. 67±11. 85, P< 0. 01) . This study confirms that EA can promote the expression of NGB in the temporal cortex of BE rats, then activate the PI3K/AKT pathway to exert its neuroprotective function and inhibit the occurrence of apoptosis. EA may become a potential treatment method for BE.

Structural and functional properties of Antarctic fish cytoglobins-1: Cold-reactivity in multi-ligand reactions.

While the functions of the recently discovered cytoglobin, ubiquitously expressed in vertebrate tissues, remain uncertain, Antarctic fish provide unparalleled models to study novel protein traits that may arise from cold adaptation. We report here the spectral, ligand-binding and enzymatic properties (peroxynitrite isomerization, nitrite-reductase activity) of cytoglobin-1 from two Antarctic fish, Chaenocephalus aceratus and Dissostichus mawsoni, and present the crystal structure of D. mawsoni cytoglobin-1. The Antarctic cytoglobins-1 display high O2 affinity, scarcely compatible with an O2-supply role, a slow rate constant for nitrite-reductase activity, and do not catalyze peroxynitrite isomerization. Compared with mesophilic orthologues, the cold-adapted cytoglobins favor binding of exogenous ligands to the hexa-coordinated bis-histidyl species, a trait related to their higher rate constant for distal-His/heme-Fe dissociation relative to human cytoglobin. At the light of a remarkable 3D-structure conservation, the observed differences in ligand-binding kinetics may reflect Antarctic fish cytoglobin-1 specific features in the dynamics of the heme distal region and of protein matrix cavities, suggesting adaptation to functional requirements posed by the cold environment. Taken together, the biochemical and biophysical data presented suggest that in Antarctic fish, as in humans, cytoglobin-1 unlikely plays a role in O2 transport, rather it may be involved in processes such as NO detoxification.

Mn-TAT PTD-Ngb ameliorates inflammation through the elimination of damaged mitochondria and the activation of Nrf2-antioxidant signaling pathway.

Inflammation, mitochondrial dysfunction and oxidative stress are closely associated with neurological diseases. In this study, Mn-TAT PTD-Ngb, a novel artificial recombinant protein, exerted inhibitory effects on the inflammatory response and inflammasome activation. During the lipopolysaccharide (LPS)-induced inflammatory response, Mn-TAT PTD-Ngb suppressed the nuclear translocation of nuclear factor kappa B (NF-κB) and the release of proinflammatory cytokines and attenuated the phosphorylation of mitogen-activated protein kinase (MAPK). Furthermore, the recombinant protein blocked reactive oxygen species (ROS) production, abated mitochondrial dysfunction and significantly suppressed the assembly of the inflammasome, which led to the overproduction of proinflammatory cytokines IL-1ß and IL-18. Mn-TAT PTD-Ngb increased the level of nuclear factor-erythroid 2 -related factor 2 (Nrf2), which protected against oxidative stress and improved pyroptosis. Mn-TAT PTD-Ngb might be a promising drug for curing neurological diseases.

Neurogenic bladder: management of the severely impaired patient with complete urethral destruction: ileovesicostomy, suprapubic tube drainage or urinary diversion-is one treatment modality better than another?

BACKGROUND: Management of the severely impaired patient (pt) with a neurogenic bladder (NGB) and complete urethral destruction employs three therapeutic options; bladder neck closure (BNC) with ileovesicostomy, BNC with suprapubic tube (SPT) placement or in pts with an end-stage bladder, cystectomy with enteric conduit diversion. This paper was performed to test the hypothesis that pts managed with an ileovesicostomy would have the best long-term prognosis. METHODS: Patients with a NGB and complete urethral destruction managed between 1986-2018 were reviewed. Three treatment populations were assessed, pts treated with BNC with ileovesicostomy, BNC with SPT placement or cystectomy with enteric conduit diversion. A minimal follow-up interval of 2 years was necessary to be entered into the study. The number of uroseptic episodes, development of urolithiasis, the onset of new renal scars, ≥ stage 3 chronic renal failure, or need for additional surgery were recorded. Statistical evaluations used either chi-squared contingency table analysis, Fisher's exact 2-tailed tests, or Kaplan-Meier curve analysis where indicated. P values of <0.05 were considered significant. RESULTS: Ten pts were managed by cystectomy, and enteric conduit, 17 by BNC and ileovesicostomy and 21 by BNC and SPT placement, median follow up of 8 yrs (range, 2-30 yrs). No significant differences between the three groups regarding the development of urolithiasis (30%, 3/10 pts; 53%, 9/17 pts; 52%, 11/21 pts; respectively), new onset of renal scarring (30%, 6/20 kidneys; 41%, 14/34 kidneys; 45%, 19/42 kidneys; respectively) or stage 3 chronic renal failure (40%, 4/10 pts; 47%, 8/17 pts; 24%, 5/21 pts; respectively. However, the number of hospitalizations for uroseptic episodes significantly increased in patients managed with an ileal conduit (60%, 6/10 pts) and ileovesicostomy (82%; 14/17 pts) compared to those maintained with a SPT (29%, 6/21 pts) P=0.025 and 0.006, respectively. When evaluating the need for delayed surgical intervention due to either urolithiasis or other complications, a total of 50% (5/10 pts) of the patients managed by an ileal conduit, 88% (15/17 pts) of the ileovesicostomy and 52% (11/21 pts) of the patients with a SPT required additional operations. In essence, significantly more pts undergoing BNC and ileovesicostomy required delayed surgical interventions for complications arising from the surgery compared to patients managed with either a cystectomy and ileal conduit (P=0.0285) or BNC and SPT placement (P=0.0180). CONCLUSIONS: In severely impaired pts with a NGB and urinary outlet destruction, BNC and ileovesicostomy are associated with a significantly increased incidence of urosepsis and late surgical complications that required operative intervention compared to alternative treatments. This finding has resulted in the abandonment of the ileovesicostomy from our surgical armamentarium.

Intraoperative neurophysiological monitoring of the bulbocavernosus reflex during surgery for conus spinal lipoma: what are the warning criteria?

OBJECTIVEDespite the surge in the intraoperative use of the bulbocavernosus reflex (BCR) during lumbosacral surgeries, there are as yet no widely accepted BCR warning criteria for use with intraoperative neurophysiological monitoring (IONM). The author's aim was to find clinically acceptable warning criteria for use in IONM of the BCR.METHODSRecords of IONM of the BCR in 164 operations in 163 patients (median age 5 months) with a conus spinal lipoma who underwent surgery between August 2002 and May 2016 were retrospectively analyzed. The outcomes of IONM of the BCR were grouped by the residual amplitude at the end of surgery: group 1, ≥ 50%; group 2, 25%-50% (including the lower bound, but not the upper); and group 3, < 25%. Cases in which the BCR was lost were separately assessed as a subgroup of group 3. The postoperative urinary complication rate was used to verify the warning criteria zones.RESULTSThe BCR could be monitored in 149 surgeries (90.9%). There were 118 surgeries (79.2%) in group 1, 18 (12.1%) in group 2, and 13 (8.7%) in group 3. Two surgeries (11.1%) in group 2 and 6 (46.2%) in group 3 resulted in urinary complications. In the group 3 subgroup (lost BCR), all 5 surgeries resulted in urinary complications. The cutoff value of the BCR amplitude reduction was placed between groups 1 and 2 (zone 1: cutoff 50%), groups 2 and 3 (zone 2: cutoff 25%), and group 3 and its subgroup (zone 3: cutoff zero, present or lost). In zone 1, the positive predictive value (PPV) was 25.8% and the negative predictive value (NPV) was 100%. In zone 2, the PPV was 53.8% and the NPV 98.5%. In zone 3, the PPV was 100% and the NPV 97.9%. The PPV was highest in zone 3. The NPV was highest in zone 1, but its PPV was low (25.8%).CONCLUSIONSThe "lost or remained" criterion of BCR amplitude (zone 3: cutoff zero) can be used as a predictor of postoperative urinary function. As a warning criterion, the cutoff value of the BCR amplitude reduction at 75% (zone 2) may be used. This preliminary clinical report on the warning criteria for the BCR may contribute to improving the safety of surgery for conus spinal lipoma.

Neuroglobin Regulates Wnt/ß-Catenin and NFκB Signaling Pathway through Dvl1.

Neuroglobin is an endogenous neuroprotective protein, but the underlying neuroprotective mechanisms remain to be elucidated. Our previous yeast two-hybrid screening study identified that Dishevelled-1, a key hub protein of Wnt/ß-Catenin signaling, is an interaction partner of Neuroglobin. In this study, we further examined the role of Neuroglobin in regulating Dishevelled-1 and the downstream Wnt/ß-Catenin and NFκB signaling pathway. We found that Neuroglobin directly interacts with Dishevelled-1 by co-immunoprecipitation, and the two proteins are co-localized in both cytoplasma and nucleus of SK-N-SH cells. Moreover, the ectopic expression of Neuroglobin promotes the degradation of exogenous and endogenous Dishevelled-1 through the proteasomal degradation pathway. Furthermore, our results showed that Neuroglobin significantly inhibits the luciferase activity of Topflash reporter and the expression of ß-Catenin mediated by Dishevelled-1 in SK-N-SH cells. In addition, we also documented that Neuroglobin enhances TNF-α-induced NFκB activation via down-regulating Dishevelled-1. Finally, 3-(4,5-Dimethylthiazol-2-Yl)-2,5-Diphenyltetrazolium Bromide (MTT) assays showed that Neuroglobin is an important neuroprotectant that protects SK-N-SH cells from TNF-α-induced decrease in cell viability. Taken together, these findings demonstrated that Neuroglobin functions as an important modulator of the Wnt/ß-Catenin and NFκB signaling pathway through regulating Dishevelled-1.

Recurrent urinary tract infections in patients with incomplete bladder emptying: is there a role for intravesical therapy?

The goal of this review article is to discuss the etiology of recurrent urinary tract infections (UTIs) in individuals with impaired bladder emptying, evaluate existing studies regarding UTI prevention strategies in this population, and explore the published experiences with intravesical therapy for the prevention and treatment of recurrent UTIs in patients performing clean intermittent catheterization (CIC). We will also describe the intravesical antibiotic protocol utilized at our institution.

Impact of magnetic resonance imaging and urodynamic studies on the management of sacrococcygeal dimples.

OBJECTIVE Sacrococcygeal dimples in neonates and infants are of uncertain pathological import. Previously they were believed to be rarely associated with intraspinal anomalies. Recent studies using MRI, however, revealed that 6%-7% of pediatric cases of sacrococcygeal dimples were associated with anatomical tethered spinal cord (TSC). Because the prevalence of tethered cord syndrome is still unclear, there is no consensus among pediatric neurosurgeons on the management of children with sacrococcygeal dimples. The authors performed an analysis of MRI and urodynamic studies to validate their management strategy for pediatric cases of sacrococcygeal dimples. METHODS A total of 103 Japanese children (49 male and 54 female, median age 4 months, range 8 days-83 months) with sacrococcygeal dimples who were referred to the Division of Pediatric Neurosurgery between 2013 and 2015 were included in this study. The lumbosacral region of all the patients was investigated using MRI. Anatomical TSC was defined as a condition in which the caudal end of the conus medullaris is lower than the inferior border of the L2-3 intervertebral disc. Patients with minor spinal anomalies (e.g., anatomical TSC, filum lipoma, thickened filum, or filar cyst) underwent further urodynamic studies to ascertain the presence of neurogenic bladder (NGB). In this study, the presence of NGB without anatomical TSC but with other minor spinal anomalies was defined as "functional TSC." The prevalence of anatomical and functional TSC was investigated. The association of the following cutaneous findings with spinal anomalies was also assessed: 1) depth of the dimple, 2) deviation of the gluteal fold, and 3) other skin abnormalities (e.g., discoloration, angioma, or abnormal hair). RESULTS The children were classified into 4 groups: Group 1, patients with anatomical TSC; Group 2, patients with functional TSC; Group 3, patients without anatomical or functional TSC but with other minor spinal anomalies; and Group 4, patients with no spinal anomaly. There were 6 patients (5.8%) in Group 1, 8 patients (7.8%) in Group 2, 10 patients (9.7%) in Group 3, and 79 patients (76.7%) in Group 4. Twenty-four patients (23.3%; Groups 1, 2, and 3) showed MRI abnormalities, including filum lipoma (14 cases), filar cysts (5 cases), thickened filum (2 cases), and anatomical TSC without other spinal anomalies (3 cases). Untethering of the spinal cord was indicated for 14 patients (13.6%; Groups 1 and 2) with anatomical and functional TSCs. Preoperative NGB was found in 12 patients and improved postoperatively in 7 (58.3%). None of the associated lumbosacral skin findings predicted the presence of underlying spinal anomalies. CONCLUSIONS The prevalence of tethered cord syndrome among children with sacrococcygeal dimples was, for the first time, revealed to be higher than previously thought. MRI and supplemental urodynamic studies may be indicated for children with sacrococcygeal dimples to identify patients with symptomatic TSC.