Search

Background: Behavioural and psychological symptoms of dementia (BPSD) are challenging to manage, leading to caregiver burden and often to subsequent transfer of patients to a nursing home or psychiatric hospital for treatment. Eliciting favourable positive emotions should be an important goal in the treatment of negative emotions associated with BPSD. To date, no data have indicated that antipsychotic medications can improve positive emotions. BPSD are known to be associated with anxiety in patients with dementia. The traditional Chinese medicine Jia Wei Gui Pi Tang is officially indicated and approved for anxiety treatment in Japan. Methods: Here, we performed a multicentre, randomised, observer‐blind control study of the effect of Jia Wei Gui Pi Tang on BPSD in Alzheimer's disease (AD) patients. Patients with AD or AD with cerebral vascular disease were randomly divided into the Jia Wei Gui Pi Tang treatment group and the control group that received no traditional Chinese medicine. BPSD were scored using the Neuropsychiatric Inventory Nursing Home Version (NPI‐NH) and by favourable positive emotions using the Delightful Emotional Index (DEI). Results: A total of 63 participants (18 male and 45 female; mean age: 83.3 ± 6.0 years) were included in the study. Changes in NPI‐NH scores differed significantly between the two groups (one‐way analysis of variance, P < 0.001). Within the treatment group, there was a significant improvement in the NPI‐NH score from 29.8 ± 17.3 at baseline to 13.2 ± 9.4 at the endpoint (paired t‐test, P < 0.001), whereas there was no statistically significant change in the control group. Changes in DEI scores differed significantly between the two groups. Within the treatment group, there was a significant improvement in the DEI score from 24.3 ± 23.0 at baseline to 32.5 ± 21.2 at the endpoint (paired t‐test, P = 0.001), whereas there was no statistically significant change in the control group. Conclusion: The traditional Chinese medicine Jia Wei Gui Pi Tang significantly improved both BPSD and positive emotions. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) and polycythemia vera (PV) rarely coexist; the clinical manifestations and treatment of this coexistence have not been described. An 81‐year‐old woman developed MM 15 years after undergoing PV treatment and was successfully treated using bortezomib. Herein, we share our experience of treating MM under such unusual conditions. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) together with polysulfides (H2Sn, n > 2) are signalling molecules like NO with various physiological roles including regulation of neuronal transmission, vascular tone, inflammation and oxygen sensing. H2S and H2Sn diffuse to the target proteins for S‐sulfurating their cysteine residues that induces the conformational changes to alter the activity. On the other hand, 3‐mercaptopyruvate sulfurtransferase transfers sulfur from a substrate 3‐mercaptopyruvate to the cysteine residues of acceptor proteins. A similar mechanism has also been identified in S‐nitrosylation. S‐sulfuration and S‐nitrosylation by enzymes proceed only inside the cell, while reactions induced by H2S, H2Sn and NO even extend to the surrounding cells. Disturbance of signalling by these molecules as well as S‐sulfuration and S‐nitrosylation causes many nervous system diseases. This review focuses on the signalling by H2S and H2Sn with S‐sulfuration comparing to that of NO with S‐nitrosylation and discusses on their roles in physiology and pathophysiology. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2 S) is a signalling molecule that regulates neuronal transmission, vascular tone, cytoprotection, inflammatory responses, angiogenesis, and oxygen sensing. Some of these functions have recently been ascribed to its oxidized form polysulfides (H2 Sn ), which can be produced by 3-mercaptopyruvate sulfurtransferase (MPST), also known as a H2 S-producing enzyme. H2 Sn activate ion channels, tumour suppressors, transcription factors, and protein kinases. H2 Sn S-sulfurate (S-sulfhydrate) cysteine residues of these target proteins to modify their activity by inducing conformational changes through the formation of a disulfide bridge between the two cysteine residues involved. The chemical interaction between H2 S and NO also generates H2 Sn , which may be a chemical entity that exerts the synergistic effect of H2 S and NO. MPST also produces redox regulators cysteine persulfide (CysSSH), GSH persulfide (GSSH), and persulfurated proteins. In addition to MPST, haemoproteins such as haemoglobin, myoglobin, neuroglobin, and catalase as well as SOD can produce H2 Sn , and sulfide quinone oxidoreductase and cysteinyl tRNA synthetase can make GSSH and CysSSH. This review focuses on the recent progress in the study of the production and physiological roles of these persulfurated and polysulfurated molecules. LINKED ARTICLES: This article is part of a themed section on Hydrogen Sulfide in Biology & Medicine. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v177.4/issuetoc. [ABSTRACT FROM AUTHOR]

Background and Purpose: Hydrogen sulfide (H2 S) and polysulfides (H2 Sn ) are signalling molecules that mediate various physiological responses including cytoprotection. Their oxidized metabolite sulfite (SO32- ) is found in blood and tissues. However, its physiological role remains unclear. In this study, we investigated the cytoprotective effect of sulfite on neurons exposed to oxidative stress caused by high concentrations of the neurotransmitter glutamate, known as oxytosis.Experimental Approach: Concentrations of sulfite as well as those of cysteine and GSH in rats were measured by HPLC. Cytoprotective effects of sulfite on primary cultures of rat neurons against oxytosis was examined by WST-8 cytoprotective and LDH cytotoxicity assays and compared with that of H2 S, H2 Sn and thiosulfate.Key Results: Free sulfite, present at approximately 2 μM in the rat brain, converts cystine to cysteine more efficiently than H2 S and H2 Sn and facilitates transport of cysteine into cells. Physiological concentrations of sulfite protected neurons from oxytosis and were accompanied by increased intracellular concentrations of cysteine and GSH probably due to converting extracellular cystine to cysteine, more efficiently than H2 S and H2 Sn . In contrast, thiosulfate only slightly protected neurons from oxytosis.Conclusions and Implications: Our present data have shown sulfite to be a novel cytoprotective molecule against oxytosis, through maintaining cysteine levels in the extracellular milieu, leading to increased intracellular cysteine and GSH. Although there may be adverse clinical effects in sensitive individuals, our results provide a new insight into the therapeutic application of sulfite to neuronal diseases caused by oxidative stress.Linked Articles: This article is part of a themed section on Chemical Biology of Reactive Sulfur Species. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.4/issuetoc. [ABSTRACT FROM AUTHOR]

Novel multiferroic materials have attracted increasing attention in recent years. Aurivillius bismuth‐layer structured Bi4Ti3O12·nBiFeO3 (BTFO: n = 1–3, 5) compounds with potential multiferroic properties are such a compound. However, the data on these BTFOs are ambigious, inconsistent, and incomplete. Therefore BTFOs were grown into single crystals for a systematic evaluation. Their crystal structures and microstructures show that intergrowth of layer structure occurs easily in this class of material. Their ferroelectric measurements show strong anisotropy and dielectric peaks at high temperature, accompanied by an abnormal loss that corresponds to their polar phase transition. At room temperature, ferroelectric hysteresis loops were successfully measured; the loops show a strong dependence in their polarization and coercive field on different values of n and anisotropy. Magnetic measurement shows that all the single crystals display magnetic transitions at high temperatures and weak ferromagnetism at room temperature. Electron spin resonance (ESR) results show the coexistence of ferromagnetic and paramagnetic signal components in all the compounds. Scanning probe microscope measurements show magnetic domains switched together with electric domains by use of an electric field. Therefore we conclude that overall spin disorder with localized order is the character of this class of material, with observed magnetoelectric (ME) coupling. This work could also point the way to novel multiferroic materials in locally magnetic ordered systems. [ABSTRACT FROM AUTHOR]

Overexpression of high mobility group AT-hook 2 ( Hmga2), which is negatively regulated by MIRLET7 micro RNAs through 3′-untranslated region (3′UTR), causes proliferative haematopoiesis mimicking myeloproliferative neoplasms (MPNs) and contributes to progression of myelofibrosis in mice. Thus, we investigated HMGA2 mRNA expression in 66 patients with MPNs including 23 polycythaemia vera (PV), 33 essential thrombocythaemia (ET) and 10 primary myelofibrosis (PMF). HMGA2 mRNA expression, especially variant 1 with 3′UTR that contains MIRLET7-specific sites, rather than variant 2 lacking 3′UTR, is frequently deregulated due to decreased MIRLET7 expression in granulocytes from over 20% of PV and ET, and in either granulocytes or CD34+ cells from 100% of PMF. Patients with deregulated HMGA2 mRNA expression were significantly more likely to show splenomegaly, high serum lactate dehydrogenase values, and methylation of the CDKN2A promoter compared with other patients without deregulation of HMGA2. A histone deacetylase inhibitor, panobinostat, significantly increased MIRLET7 expression and reduced variant 1 of HMGA2 mRNA expression, but not variant 2, in both U937 cells and PMF-derived CD34+ cells. Moreover, both panobinostat and small interfering RNA of HMGA2 demethylated the CDKN2A promoter in U937 cells. In conclusion, the frequently dysregulated MIRLET7/ HMGA2 axis could be a therapeutic target in MPNs. [ABSTRACT FROM AUTHOR]

For practical application, the functional piezoelectric film in microelectromechanical systems should meet the requirement of physical properties, as well as the mechanical properties. In this article, 0.5 Ba( Ti0.8 Zr0.2) O3-0.5( Ba0.7 Ca0.3) TiO3 (0.5 BZT-0.5 BCT) thin films with varied properties were prepared on (100) Si substrates via a sol-gel technique at different annealing temperatures. The effects of the annealing temperature on the morphology, piezoelectricity, hardness, and elastic modulus were studied. Particular attention was paid to the surface frictional behavior of films, and the changes in the friction force can be radically explained in terms of differences in the hardness/elastic modulus ratio and the residual stress of films. And, it reveals that the higher ratio of hardness to elastic modulus and tensile residual stress can contribute to a lower friction force for 0.5 BZT-0.5 BCT film during sling friction. [ABSTRACT FROM AUTHOR]

Highlights: [•] Polysulfide uptake induces acceleration of GSH synthesis and HO-1 expression. [•] Polysulfide possesses cytoprotective function against ROS toxicity in the cell. [•] Polysulfide-induced disulfide formation of Keap1 causes Nrf2 activation. [•] The PI3K/Akt phosphorylation pathway is activated by polysulfide. [ABSTRACT FROM AUTHOR]

Accumulating evidence shows that hydrogen sulfide (H2S) has a variety of physiological functions. H2S is produced from cysteine by 3 sulfur-transferases. H2S, in turn, generates polysulfides, the functions of which are not well understood. H2S induces Ca2+ influx in astrocytes, a type of glia. However, the receptor that mediates the response has not been identified. Here, we have shown that polysulfides induce Ca2+ influx by activating transient receptor potential (TRP)A1 channels in rat astrocytes (EC50 91 nM, Hill coefficient value 1.77±0.26) and that the maximum response was induced at 0.5 wM, which is 1/320 of the concentration of H2S required to achieve a response of similar magnitude (160 µM, EC50 116 µM). TRPA1-selective agonists, allyl isothiocyanate and cinnamaldehyde, induced Ca2+ influx, and responses to polysulfides were suppressed by TRPAl-selective inhibitors, HC-030031 and AP-18, as well as by siRNAs selective to TRPA1. The present study suggests that polysulfides are possible H2S-derived signaling molecules that stimulate TRP channels in the brain. [ABSTRACT FROM AUTHOR]

ZnO/Co multilayers were fabricated on silicate (100) substrate by a pulsed laser deposition method at room temperature. The x-ray diffraction (XRD) results reveal that the as-deposited multilayer film is composed of amorphous phase, which leads to high saturation magnetization and low coercivity. Higher coercivity is observed in the ZnO/Co films annealed at 390 °C due to the formation of crystalline metallic Co and semiconducting ZnO. But much higher annealing temperature leads to the oxidation of metallic Co and the reaction between Co and ZnO, which decreases the saturation magnetization and coercivity obviously. [ABSTRACT FROM AUTHOR]

Abstract: We examined the expression of the major H2S-producing enzymes, cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE). CBS was ubiquitously distributed in the mouse pancreas, but CSE was found only in the exocrine. Freshly isolated islets expressed CBS, while CSE was faint. However, high glucose increased the CSE expression in the beta-cells. l-Cysteine or NaHS suppressed islet cell apoptosis with high glucose, and increased glutathione content in MIN6 beta-cells. Pretreatment with l-cysteine improved the secretory responsiveness following stimulation with glucose. The CSE inhibitor dl-propargylglycine antagonized these l-cysteine effects. We suggest H2 S may function as an ‘intrinsic brake’ which protects beta-cells from glucotoxicity. [Copyright &y& Elsevier]

We have demonstrated a synthetic procedure for nano-sized NaNbO3 powder and its thin films using a carbon-free precursor prepared by the reaction of H2O2 with sodium and niobium alkoxides. A combination of X-ray powder diffraction, Raman spectra, and thermal gravity and differential thermal analysis, carbon analysis, fourier transform infrared spectra, transmission electron microscopy, and atomic force microscopy was used to characterize the resulting materials and precursor compounds. Results show that this procedure demonstrates the major advantages of low-temperature synthesis (∼400°C) and low weight loss during transformation into NaNbO3 because of its carbon-free nature, which also provides the option of preparing nano-sized particles and dense, crack-free NaNbO3 thin films. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H[sub 2]S) is endogenously produced in the brain from L-cysteine by the enzyme cystathionine β-synthase (CBS) and functions as a neuromodulator in the brain. H[sub 2]S selectively enhances NMDA receptor-mediated responses and alters hippocampal long-term potentiation (LTP). The production of H[sub 2]S is regulated by Ca[sup 2+]/calmodulin-mediated pathways and is enhanced in response to neuronal excitation. In addition to this fast regulation, we describe here a slower form of the regulation of H[sub 2]S production by testosterone and S-adenosyl-L-methionine (SAM), a CBS activator. Endogenous H[sub 2]S in the mouse brain increases after birth, reaches a maximum level at 8 weeks and then decreases. Female brain contains less H[sub 2]S than male brain at each age. A single administration of testosterone to female mice increases the endogenous H[sub 2]S and SAM, which reach levels similar to those of male mice. In contrast, castration of male mice decreases the levels of testosterone, SAM and H[sub 2]S in the brain. Administration of SAM once a day for 3 days increases the brain H[sub 2]S without significantly changing the testosterone level. These observations suggest that testosterone can regulate the brain H[sub 2]S level via changing the level of SAM. [ABSTRACT FROM AUTHOR]

A novel presenilin-binding protein (PBP) is specifically expressed in the brain, and its level in the soluble fraction of Alzheimer's disease (AD) brains is much less than that in the age-matched controls. Recently, several proteins, including presenilin (PS), have been found to form structures of aggregated proteins, called aggresomes, when the production of the proteins exceeds their rate of degradation by proteasomes. Based on these observations it has been proposed that the aggresome may represent one of the mechanisms for the formation of cytoplasmic deposits which are linked to the pathogenesis of neurodegenerative disorders including AD. It is shown here that the overexpression of PBP or the suppression of proteasome activity in monkey kidney COS-7 cells leads to the accumulation of detergent-insoluble and multiubiquitinated PBP aggregates. PBP also forms aggregates in primary cultures of neurons in the presence of a proteasome inhibitors. PBP aggregates have the characteristics of aggresomes, including the localization to microtubule organization centers and the disruption of intermediate filaments. These observations suggest that the malfunctioning of the proteasome can cause the formation of PBP aggresomes, which may lead to AD. [ABSTRACT FROM AUTHOR]

Approximately 50% of familial Alzheimer's disease (AD) cases are linked to the presenilin (PS) gene. This suggests that an altered function of mutated PSs accounts for a fundamental process leading to AD. Here we identify a new PS binding protein, PBP, which is highly expressed in cerebral cortex and hippocampus. immunohistochemical studies and cell fractionation analysis show that PBP redistributes from cytoplasm to membranes in the presence of PS. In addition, PBP is deficient in the soluble fraction of sporadic AD brains. [ABSTRACT FROM AUTHOR]

Endogenous levels of sulfide in the brain have been measured in rats, humans and bovines in 1989 and 1990, suggesting that H2S may have a physiological function. We demonstrated in 1996 that cystathionine β-synthase can produce H2S in the brain and that H2S facilitates the induction of hippocampal long-term potentiation by enhancing the activity of NMDA receptors. The following year, we showed that another H2S-producing enzyme, cystathionine γ-lyase, is expressed in the thoracic aorta, portal vein and ileum and that H2S relaxes these tissues. We proposed that H2S may be a neuromodulator as well as a smooth muscle relaxant. In addition to a function as a signalling molecule, we demonstrated another function as a cytoprotectant in 2004. Hydrogen sulfide protects neurons from oxidative stress by reinstating the reduced glutathione levels. We recently demonstrated that a third H2S-producing enzyme, 3-mercaptopyruvate sulfurtransferase (3MST), is expressed in neurons and vascular endothelium. In addition to reinstating glutathione levels, H2S produced by 3MST, which is mainly localized to mitochondria, reduces reactive oxygen species generated in these organelles. [ABSTRACT FROM AUTHOR]

Examines the regional and cellular expression of cystathionine β-synthase (CBS) in the developing and adult mouse central nervous system to elucidate the role of CBS in the nervous system. Effect of CBS deficiency on the normal development of brain; CBS expression in the radial glia/astrocyte lineage in the adult and developing mouse brain; CBS expression after kainic acid-induced seizures which represent an animal model for human temporal lobe epilepsy.

A novel aqueous chemical solution was developed as a precursor both for LiNbO3 powder and thin film. In this method, hydrogen peroxide aqueous solution (H2O2) reacts with niobium and lithium alkoxide ethanol solution to form metal peroxide aqueous solution. From this solution, crystalline LiNbO3 were synthesized at a temperature as low as 350°C. LiNbO3 thin films with well-developed grains were fabricated by spin-coating on silicon and sapphire substrates. In comparison with the alkoxide solution method, this peroxide solution method provides significant advantages, such as low weight loss in the sintering process and easy handling. [ABSTRACT FROM AUTHOR]

Deals with a study which examined the role of hydrogen sulfide in protecting neurons from oxidative stress. Influence of hydrogen sulfide on the production of glutathione; Effect of hydrogen sulfide on &gamma-glutamylcysteine; Significance of hydrogen sulfide to cystine transport.

Examines a role for hydrogen sulfide in calcium waves induced in astrocytes. Difference in the time course of the increase in intracellular Ca2+ between the astrocytes exposed directly to hydrogen sulfide and those activated by the propagated Ca2+; Interactions between neurons and glia; Conclusions and significance.

Questions: How does the severity of prescribed fires affect vegetation and seed bank in a wetland? Location: A fire-prone reed swamp in northern Japan (250 ha, 40°49′N, 141°22′E, <10 m a.s.l.). Methods: Vegetation, biomass and seed bank were monitored for the 2 yr after annual prescribed fires were discontinued. Plant communities were placed into three categories based on fire severity: high (H) - fire consumed litter completely; moderate (M) - fire removed standing litter but left wet fallen litter; and low (L) - fire incompletely removed standing litter and did not remove fallen litter. Soil samples were collected in autumn 2007 and early summer 2008, and germinable seed bank was investigated by greenhouse trials. Results: High fire severity increased diversity in the next growing season by the establishment of short herbs in the standing vegetation. The biomass of forbs and grasses was greater in H where Phragmites australis biomass was reduced. The density of seed bank was >30 000 seeds m−2 throughout all the treatments. Perennial plants were dominant in the vegetation, while annuals, biennials and rushes were dominant in the seed bank. Small seeds were more abundant in the soil than in the litter. Qualitative and quantitative similarities between seed bank and the vegetation were low, and tended to be higher in H. Conclusions: Fire contributed to the development of diverse standing vegetation via the positive effects on seed bank dynamics, and can be considered a tool to maintain species-rich marshes. [ABSTRACT FROM AUTHOR]

Presents a corrected version of the article "The production of hydrogen sulfide is regulated by testosterone and S-adenosyl-l-methionine in mouse brain," by Ko Eto and Hideo Kimura.

Mice with the C3H background show greater behavioral propensity for schizophrenia, including lower prepulse inhibition (PPI), than C57BL/6 (B6) mice. To characterize as-yet-unknown pathophysiologies of schizophrenia, we undertook proteomics analysis of the brain in these strains, and detected elevated levels of Mpst, a hydrogen sulfide (H 2 S)/polysulfide-producing enzyme, and greater sulfide deposition in C3H than B6 mice. Mpst-deficient mice exhibited improved PPI with reduced storage sulfide levels, while Mpst-transgenic (Tg) mice showed deteriorated PPI, suggesting that "sulfide stress" may be linked to PPI impairment. Analysis of human samples demonstrated that the H 2 S/polysulfides production system is upregulated in schizophrenia. Mechanistically, the Mpst-Tg brain revealed dampened energy metabolism, while maternal immune activation model mice showed upregulation of genes for H 2 S/polysulfides production along with typical antioxidative genes, partly via epigenetic modifications. These results suggest that inflammatory/oxidative insults in early brain development result in upregulated H 2 S/polysulfides production as an antioxidative response, which in turn cause deficits in bioenergetic processes. Collectively, this study presents a novel aspect of the neurodevelopmental theory for schizophrenia, unraveling a role of excess H 2 S/polysulfides production., (© 2019 The Authors. Published under the terms of the CC BY 4.0 license.)

Overexpression of high mobility group AT-hook 2 (Hmga2), which is negatively regulated by MIRLET7 micro RNAs through 3'-untranslated region (3'UTR), causes proliferative haematopoiesis mimicking myeloproliferative neoplasms (MPNs) and contributes to progression of myelofibrosis in mice. Thus, we investigated HMGA2 mRNA expression in 66 patients with MPNs including 23 polycythaemia vera (PV), 33 essential thrombocythaemia (ET) and 10 primary myelofibrosis (PMF). HMGA2 mRNA expression, especially variant 1 with 3'UTR that contains MIRLET7-specific sites, rather than variant 2 lacking 3'UTR, is frequently deregulated due to decreased MIRLET7 expression in granulocytes from over 20% of PV and ET, and in either granulocytes or CD34(+) cells from 100% of PMF. Patients with deregulated HMGA2 mRNA expression were significantly more likely to show splenomegaly, high serum lactate dehydrogenase values, and methylation of the CDKN2A promoter compared with other patients without deregulation of HMGA2. A histone deacetylase inhibitor, panobinostat, significantly increased MIRLET7 expression and reduced variant 1 of HMGA2 mRNA expression, but not variant 2, in both U937 cells and PMF-derived CD34(+) cells. Moreover, both panobinostat and small interfering RNA of HMGA2 demethylated the CDKN2A promoter in U937 cells. In conclusion, the frequently dysregulated MIRLET7/HMGA2 axis could be a therapeutic target in MPNs., (© 2014 John Wiley & Sons Ltd.)