Displaying publications 2401 - 2420 of 9219 in total

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  1. LPS Preconditioning Attenuates Apoptosis Mechanism by Inhibiting NF-κB and Caspase-3 Activity: TLR4 Pre-activation in the Signaling Pathway of LPS-Induced Neuroprotection
    Sangaran PG, Ibrahim ZA, Chik Z, Mohamed Z, Ahmadiani A
    Mol Neurobiol, 2021 May;58(5):2407-2422.
    PMID: 33421016 DOI: 10.1007/s12035-020-02227-3
    Neuroinflammation, an inflammatory response within the nervous system, has been shown to be implicated in the progression of various neurodegenerative diseases. Recent in vivo studies showed that lipopolysaccharide (LPS) preconditioning provides neuroprotection by activating Toll-like receptor 4 (TLR4), one of the members for pattern recognition receptor (PRR) family that play critical role in host response to tissue injury, infection, and inflammation. Pre-exposure to low dose of LPS could confer a protective state against cellular apoptosis following subsequent stimulation with LPS at higher concentration, suggesting a role for TLR4 pre-activation in the signaling pathway of LPS-induced neuroprotection. However, the precise molecular mechanism associated with this protective effect is not well understood. In this article, we provide an overall review of the current state of our knowledge about LPS preconditioning in attenuating apoptosis mechanism and conferring neuroprotection via TLR4 signaling pathway.
    Matched MeSH terms: NF-kappa B/metabolism*; Toll-Like Receptor 4/metabolism*; Caspase 3/metabolism*
  2. Fulltext Neuroprotective Effects and Therapeutic Potential of Transcorneal Electrical Stimulation for Depression
    Yu WS, Kwon SH, Agadagba SK, Chan LL, Wong KH, Lim LW
    Cells, 2021 09 21;10(9).
    PMID: 34572141 DOI: 10.3390/cells10092492
    Transcorneal electrical stimulation (TES) has emerged as a non-invasive neuromodulation approach that exerts neuroprotection via diverse mechanisms, including neurotrophic, neuroplastic, anti-inflammatory, anti-apoptotic, anti-glutamatergic, and vasodilation mechanisms. Although current studies of TES have mainly focused on its applications in ophthalmology, several lines of evidence point towards its putative use in treating depression. Apart from stimulating visual-related structures and promoting visual restoration, TES has also been shown to activate brain regions that are involved in mood alterations and can induce antidepressant-like behaviour in animals. The beneficial effects of TES in depression were further supported by its shared mechanisms with FDA-approved antidepressant treatments, including its neuroprotective properties against apoptosis and inflammation, and its ability to enhance the neurotrophic expression. This article critically reviews the current findings on the neuroprotective effects of TES and provides evidence to support our hypothesis that TES possesses antidepressant effects.
    Matched MeSH terms: Cornea/metabolism; Retina/metabolism; Neuroprotective Agents/metabolism
  3. Strain differences in intermale aggression and possible factors regulating increased aggression in Japanese quail
    Maekawa F, Nagino K, Yang J, Htike NTT, Tsukahara S, Ubuka T, et al.
    Gen Comp Endocrinol, 2018 01 15;256:63-70.
    PMID: 28765073 DOI: 10.1016/j.ygcen.2017.07.025
    The National Institute for Environmental Studies (NIES) of Japan established a strain of Japanese quail (Coturnix japonica) known as NIES-L by rotation breeding in a closed colony for over 35years; accordingly, the strain has highly inbred-like characteristics. Another strain called NIES-Brn has been maintained by randomized breeding in a closed colony to produce outbred-like characteristics. The current study aimed to characterize intermale aggressive behaviors in both strains and to identify possible factors regulating higher aggression in the hypothalamus, such as sex hormone and neuropeptide expression. Both strains displayed a common set of intermale aggressive behaviors that included pecking, grabbing, mounting, and cloacal contact behavior, although NIES-Brn quail showed significantly more grabbing, mounting, and cloacal contact behavior than did NIES-L quail. We examined sex hormone levels in the blood and diencephalon in both strains. Testosterone concentrations were significantly higher in the blood and diencephalon of NIES-Brn quail compared to NIES-L quail. We next examined gene expression in the hypothalamus of both strains using an Agilent gene expression microarray and real-time RT-PCR and found that gene expression of mesotocin (an oxytocin homologue) was significantly higher in the hypothalamus of NIES-Brn quail compared to NIES-L quail. Immunohistochemistry of the hypothalamus revealed that numbers of large cells (cell area>500μm2) expressing mesotocin were significantly higher in the NIES-Brn strain compared to the NIES-L strain. Taken together, our findings suggest that higher testosterone and mesotocin levels in the hypothalamus may be responsible for higher aggression in the NIES-Brn quail strain.
    Matched MeSH terms: Hypothalamus/metabolism; Oxytocin/metabolism; RNA, Messenger/metabolism
  4. Caffeine neuroprotects against dexamethasone-induced anxiety-like behaviour in the Zebrafish (Danio rerio)
    Khor YM, Soga T, Parhar IS
    Gen Comp Endocrinol, 2013 Jan 15;181:310-5.
    PMID: 23044054 DOI: 10.1016/j.ygcen.2012.09.021
    The early-life stress has critical impact on brain development which can lead to long-term effects on brain functions during adulthood. It has been reported that caffeine possesses a protective effect in neurodegenerative diseases. Thus, this study investigates the potential of caffeine to protect brain functions from adverse effects due to stress exposure during early-life development in the male zebrafish. In the first part of this study, synthetic glucocorticoid, dexamethasone (DEX) (2-200 mg/L for 24 h) was used to induce stress effects in the zebrafish larvae from 4 to 5 days post-fertilisation (dpf) and the effect of DEX administration on zebrafish larvae on anxiety-like behaviour during adulthood in novel tank test was investigated. Next, the possible protective effect of caffeine pre-treatment (5-50 mg/L for 24 h from 3 to 4dpf) before DEX administration was studied. DEX-treated adult male zebrafish showed higher anxiety levels in behavioural tests, as seen in longer latency to enter the top part of the tank, lower transition numbers between the top and bottom parts with more time spent at the bottom and lesser time spent at the top and lower distance travelled at top part. The effect of DEX on anxiety-like behaviour was dose-dependent. Importantly, adult male zebrafish pre-treated with caffeine before DEX treatment did not show any anxiety-like behaviour. These results show that exposure to stress during early-life leads to anxiety-like behaviour in the adult male zebrafish but pre-treatment with caffeine protects from stress-induced anxiety.
    Matched MeSH terms: Hydrocortisone/metabolism; Hypothalamus/metabolism; Receptors, Glucocorticoid/metabolism
  5. Notch signaling and ghost cell fate in the calcifying cystic odontogenic tumor
    Siar CH, Kawakami T, Buery RR, Nakano K, Tomida M, Tsujigiwa H, et al.
    Eur J Med Res, 2011 Nov 10;16(11):501-6.
    PMID: 22027644
    Notch signaling is an evolutionarily conserved mechanism that enables adjacent cells to adopt different fates. Ghost cells (GCs) are anucleate cells with homogeneous pale eosinophilic cytoplasm and very pale to clear central areas (previous nucleus sites). Although GCs are present in a variety of odontogenic lesions notably the calcifying cystic odontogenic tumor (CCOT), their nature and process of formation remains elusive. The aim of this study was to investigate the role of Notch signaling in the cell fate specification of GCs in CCOT. Immunohistochemical staining for four Notch receptors (Notch1, Notch2, Notch3 and Notch4) and three ligands (Jagged1, Jagged2 and Delta1) was performed on archival tissues of five CCOT cases. Level of positivity was quantified as negative (0), mild (+), moderate (2+) and strong (3+). Results revealed that GCs demonstrated overexpression for Notch1 and Jagged1 suggesting that Notch1-Jagged1 signaling might serve as the main transduction mechanism in cell fate decision for GCs in CCOT. Protein localizations were largely membranous and/or cytoplasmic. Mineralized GCs also stained positive implicating that the calcification process might be associated with upregulation of these molecules. The other Notch receptors and ligands were weak to absent in GCs and tumoral epithelium. Stromal endothelium and fibroblasts were stained variably positive.
    Matched MeSH terms: Odontogenic Tumors/metabolism*; Odontogenic Cyst, Calcifying/metabolism*; Receptors, Notch/metabolism*
  6. Fulltext The Duffy binding protein (PkDBPαII) of Plasmodium knowlesi from Peninsular Malaysia and Malaysian Borneo show different binding activity level to human erythrocytes
    Lim KL, Amir A, Lau YL, Fong MY
    Malar J, 2017 08 11;16(1):331.
    PMID: 28800732 DOI: 10.1186/s12936-017-1984-8
    BACKGROUND: The zoonotic Plasmodium knowlesi is a major cause of human malaria in Malaysia. This parasite uses the Duffy binding protein (PkDBPαII) to interact with the Duffy antigen receptor for chemokines (DARC) receptor on human and macaque erythrocytes to initiate invasion. Previous studies on P. knowlesi have reported distinct Peninsular Malaysia and Malaysian Borneo PkDBPαII haplotypes. In the present study, the differential binding activity of these haplotypes with human and macaque (Macaca fascicularis) erythrocytes was investigated.

    METHODS: The PkDBPαII of Peninsular Malaysia and Malaysian Borneo were expressed on the surface of COS-7 cells and tested with human and monkey erythrocytes, with and without anti-Fy6 (anti-Duffy) monoclonal antibody treatment. Binding activity level was determined by counting the number of rosettes formed between the transfected COS-7 cells and the erythrocytes.

    RESULTS: Anti-Fy6 treatment was shown to completely block the binding of human erythrocytes with the transfected COS-7 cells, thus verifying the specific binding of human DARC with PkDBPαII. Interestingly, the PkDBPαII of Peninsular Malaysia displayed a higher binding activity with human erythrocytes when compared with the Malaysian Borneo PkDBPαII haplotype (mean number of rosettes formed = 156.89 ± 6.62 and 46.00 ± 3.57, respectively; P 

    Matched MeSH terms: Carrier Proteins/metabolism*; Protozoan Proteins/metabolism*; Plasmodium knowlesi/metabolism*
  7. Fulltext Transcriptomic analysis of the role of RasGEF1B circular RNA in the TLR4/LPS pathway
    Ng WL, Marinov GK, Chin YM, Lim YY, Ea CK
    Sci Rep, 2017 09 25;7(1):12227.
    PMID: 28947785 DOI: 10.1038/s41598-017-12550-w
    Circular RNAs (circRNAs) have recently emerged as a large class of novel non-coding RNA species. However, the detailed functional significance of the vast majority of them remains to be elucidated. Most functional characterization studies targeting circRNAs have been limited to resting cells, leaving their role in dynamic cellular responses to stimuli largely unexplored. In this study, we focus on the LPS-induced cytoplasmic circRNA, mcircRasGEF1B, and combine targeted mcircRasGEF1B depletion with high-throughput transcriptomic analysis to gain insight into its function during the cellular response to LPS stimulation. We show that knockdown of mcircRasGEF1B results in altered expression of a wide array of genes. Pathway analysis revealed an overall enrichment of genes involved in cell cycle progression, mitotic division, active metabolism, and of particular interest, NF-κB, LPS signaling pathways, and macrophage activation. These findings expand the set of functionally characterized circRNAs and support the regulatory role of mcircRasGEF1B in immune response during macrophage activation and protection against microbial infections.
    Matched MeSH terms: Lipopolysaccharides/metabolism*; RNA/metabolism*; Toll-Like Receptor 4/metabolism*
  8. Estimation and influence of physicochemical properties and chemical fractions of surface sediment on the bioaccessibility of Cd and Hg contaminant in Langat River, Malaysia
    Kadhum SA, Ishak MY, Zulkifli SZ
    Environ Geochem Health, 2017 Oct;39(5):1145-1158.
    PMID: 27848092 DOI: 10.1007/s10653-016-9883-4
    This study applied the use of sequential extraction technique and simple bioaccessibility extraction test to quantify the bioavailable fractions and the human bioaccessible concentration of metals collected from nine stations in surface sediment of the Langat River. The concentrations of total and bioaccessible metals from different stations were in the range of 0.49-1.04, 0.10-0.32 μg g-1 for T-Cd, Bio-Cd, respectively, and 12.9-128.03, 2.06-8.53 μg kg-1 for T-Hg, Bio-Hg, respectively. The results revealed highest R-Bio-Cd in Banting station (55.3 %), while the highest R-Bio-Hg was in Kajang station (49.61 %). The chemical speciation of Cd in most sampling stations was in the order of oxidisable-organic > residual > exchangeable > acid-reducible, while speciation of Hg was in the order of exchangeable > residual > oxidisable-organic > acid-reducible. The correlation matric of mean content showed that the TOM, particle size and Mg++ in polluted surface sediments was highly correlated with total mercury. The PCA showed that the main factors influencing the bioaccessibility of Hg in surface sediments were the sediment TOM, F1 (EFLE) and F3 (oxidation-organic), while the factor influencing the bioaccessibility of Cd was the F3 (oxidation-organic) and T-Cd.
    Matched MeSH terms: Cadmium/metabolism*; Mercury/metabolism*; Water Pollutants, Chemical/metabolism*
  9. Fulltext JMJD8 is a novel endoplasmic reticulum protein with a JmjC domain
    Yeo KS, Tan MC, Lim YY, Ea CK
    Sci Rep, 2017 11 13;7(1):15407.
    PMID: 29133832 DOI: 10.1038/s41598-017-15676-z
    Jumonji C (JmjC) domain-containing proteins have been shown to regulate cellular processes by hydroxylating or demethylating histone and non-histone targets. JMJD8 belongs to the JmjC domain-only family that was recently shown to be involved in angiogenesis and TNF-induced NF-κB signaling. Here, we employed bioinformatic analysis and immunofluorescence microscopy to examine the physiological properties of JMJD8. We demonstrated that JMJD8 localizes to the lumen of endoplasmic reticulum and that JMJD8 forms dimers or oligomers in vivo. Furthermore, we identified potential JMJD8-interacting proteins that are known to regulate protein complex assembly and protein folding. Taken together, this work demonstrates that JMJD8 is the first JmjC domain-containing protein found in the lumen of the endoplasmic reticulum that may function in protein complex assembly and protein folding.
    Matched MeSH terms: Endoplasmic Reticulum/metabolism*; Oxidoreductases, N-Demethylating/metabolism*; Jumonji Domain-Containing Histone Demethylases/metabolism*
  10. Aspergillus terreus treated rice straw suppresses methane production and enhances feed digestibility in goats
    Mohd Azlan P, Jahromi MF, Ariff MO, Ebrahimi M, Candyrine SCL, Liang JB
    Trop Anim Health Prod, 2018 Mar;50(3):565-571.
    PMID: 29150805 DOI: 10.1007/s11250-017-1470-x
    The objectives of this study were to test the efficacy of producing lovastatin in rice straw treated with Aspergillus terreus in larger laboratory scale following the procedure previously reported and to investigate the effectiveness of the treated rice straw containing lovastatin on methane mitigation in goats. The concentration of lovastatin in the treated rice straw was 0.69 ± 0.05 g/kg dry matter (DM) rice straw. Our results showed that supplementation of lovastatin at 4.14 mg/kg BW reduced methane production by 32% while improving the DM digestibility by 13% (P 
    Matched MeSH terms: Aspergillus/metabolism*; Methane/metabolism; Rumen/metabolism*
  11. Fulltext Oxidative Stress in Cardiovascular Diseases: Involvement of Nrf2 Antioxidant Redox Signaling in Macrophage Foam Cells Formation
    Ooi BK, Goh BH, Yap WH
    Int J Mol Sci, 2017 Nov 05;18(11).
    PMID: 29113088 DOI: 10.3390/ijms18112336
    Oxidative stress is an important risk factor contributing to the pathogenesis of cardiovascular diseases. Oxidative stress that results from excessive reactive oxygen species (ROS) production accounts for impaired endothelial function, a process which promotes atherosclerotic lesion or fatty streaks formation (foam cells). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor involved in cellular redox homeostasis. Upon exposure to oxidative stress, Nrf2 is dissociated from its inhibitor Keap-1 and translocated into the nucleus, where it results in the transcriptional activation of cell defense genes. Nrf2 has been demonstrated to be involved in the protection against foam cells formation by regulating the expression of antioxidant proteins (HO-1, Prxs, and GPx1), ATP-binding cassette (ABC) efflux transporters (ABCA1 and ABCG1) and scavenger receptors (scavenger receptor class B (CD36), scavenger receptor class A (SR-A) and lectin-type oxidized LDL receptor (LOX-1)). However, Nrf2 has also been reported to exhibit pro-atherogenic effects. A better understanding on the mechanism of Nrf2 in oxidative stress-induced cardiac injury, as well as the regulation of cholesterol uptake and efflux, are required before it can serve as a novel therapeutic target for cardiovascular diseases prevention and treatment.
    Matched MeSH terms: Cardiovascular Diseases/metabolism*; Foam Cells/metabolism*; NF-E2-Related Factor 2/metabolism*
  12. s8ORF2 protein of infectious salmon anaemia virus is a RNA-silencing suppressor and interacts with Salmon salar Mov10 (SsMov10) of the host RNAi machinery
    Thukral V, Varshney B, Ramly RB, Ponia SS, Mishra SK, Olsen CM, et al.
    Virus Genes, 2018 Apr;54(2):199-214.
    PMID: 29218433 DOI: 10.1007/s11262-017-1526-z
    The infectious salmon anaemia virus (ISAV) is a piscine virus, a member of Orthomyxoviridae family. It encodes at least 10 proteins from eight negative-strand RNA segments. Since ISAV belongs to the same virus family as Influenza A virus, with similarities in protein functions, they may hence be characterised by analogy. Like NS1 protein of Influenza A virus, s8ORF2 of ISAV is implicated in interferon antagonism and RNA-binding functions. In this study, we investigated the role of s8ORF2 in RNAi suppression in a well-established Agrobacterium transient suppression assay in stably silenced transgenic Nicotiana xanthi. In addition, s8ORF2 was identified as a novel interactor with SsMov10, a key molecule responsible for RISC assembly and maturation in the RNAi pathway. This study thus sheds light on a novel route undertaken by viral proteins in promoting viral growth, using the host RNAi machinery.
    Matched MeSH terms: RNA-Binding Proteins/metabolism*; Viral Nonstructural Proteins/metabolism*; Fish Proteins/metabolism*
  13. Inhibition and kinetic studies of cellulose- and hemicellulose-degrading enzymes of Ganoderma boninense by naturally occurring phenolic compounds
    Surendran A, Siddiqui Y, Ali NS, Manickam S
    J Appl Microbiol, 2018 Jun;124(6):1544-1555.
    PMID: 29405525 DOI: 10.1111/jam.13717
    AIM: Ganoderma sp, the causal pathogen of the basal stem rot (BSR) disease of oil palm, secretes extracellular hydrolytic enzymes. These play an important role in the pathogenesis of BSR by nourishing the pathogen through the digestion of cellulose and hemicellulose of the host tissue. Active suppression of hydrolytic enzymes secreted by Ganoderma boninense by various naturally occurring phenolic compounds and estimation of their efficacy on pathogen suppression is focused in this study.

    METHODS AND RESULTS: Ten naturally occurring phenolic compounds were assessed for their inhibitory effect on the hydrolytic enzymes of G. boninense. The enzyme kinetics (Vmax and Km ) and the stability of the hydrolytic enzymes were also characterized. The selected compounds had shown inhibitory effect at various concentrations. Two types of inhibitions namely uncompetitive and noncompetitive were observed in the presence of phenolic compounds. Among all the phenolic compounds tested, benzoic acid was the most effective compound suppressive to the growth and production of hydrolytic enzymes secreted by G. boninense. The phenolic compounds as inhibitory agents can be a better replacement for the metal ions which are known as conventional inhibitors till date. The three hydrolytic enzymes were stable in a wide range of pH and temperature.

    CONCLUSION: These findings highlight the efficacy of the applications of phenolic compounds to control Ganoderma.

    SIGNIFICANCE AND IMPACT OF THE STUDY: The study has proved a replacement for chemical controls of G. boninense with naturally occurring phenolic compounds.

    Matched MeSH terms: Cellulose/metabolism*; Fungal Proteins/metabolism; Polysaccharides/metabolism*
  14. First report of bioaccumulation and bioconcentration of aliphatic hydrocarbons (AHs) and persistent organic pollutants (PAHs, PCBs and PCNs) and their effects on alcyonacea and scleractinian corals and their endosymbiotic algae from the Persian Gulf, Iran: Inter and intra-species differences
    Ranjbar Jafarabadi A, Riyahi Bakhtiari A, Aliabadian M, Laetitia H, Shadmehri Toosi A, Yap CK
    Sci Total Environ, 2018 Jun 15;627:141-157.
    PMID: 29426136 DOI: 10.1016/j.scitotenv.2018.01.185
    The coral reefs of the Persian Gulf are the most diverse systems of life in the marine environment of the Middle East. Unfortunately, they are highly threatened by local and global stressors, particularly oil pollutants. This is the first quantitative and qualitative study aimed at assessing the concentration and sources of n-alkanes and POPs (PAHs, PCBs and PCNs) in coral tissues, symbiotic algae (zooxanthellae), reef sediments and seawaters in coral reefs of Lark and Kharg in the Persian Gulf, Iran. This work was conducted on eight species of six genera and three families of hard corals and one family of soft coral. A significant variation in the concentration of ∑30n-alkanes and POPs (∑40PAHs, ∑22PCBs and 20PCNs) was found in the decreasing order: zooxanthellae > coral tissue > skeleton > reef sediment > seawater. The bioaccumulation of these compounds was 2-times higher in ahermatypic than in hermatypic corals, among which significant variations were observed in both sites. In Kharg, Porites lutea had the highest mean concentration of ∑30n-alkanes and ∑40PAHs in soft tissue, whereas the lowest values were in Platygyra daedalea. A contrasting trend was documented for ∑22PCBs and 20PCNs, with the highest level reported in soft tissue of P. daedalea and the lowest in P. lutea at Kharg. Compositional pattern of AHs and PAHs demonstrated the predominance of LMW-PAHs and n-alkanes. In skeleton and reef sediments, tetra, penta and tri-CBs were the most abundant PCBs congeners followed by di-CB > hexa-CB > hepta-CB > octa-CB,whiletri-CB > di-CB > tetra-CB > penta-CB > hexa-CB > hepta-CB > octa-CB was observed for soft tissue, zooxanthellae and seawater. The results of RAD test indicated significantly negative correlation between total concentration of these compounds with zooxanthellae density, the chlorophyll-a and C2 in corals at both reefs. This is the first report on levels, health assessment and source apportionments of POPs in zooxanthellae and a first step in the implementation of specific coral reef management measures.
    Matched MeSH terms: Hydrocarbons/metabolism*; Polychlorinated Biphenyls/metabolism; Water Pollutants, Chemical/metabolism*
  15. Fate, uptake, and distribution of nanoencapsulated pesticides in soil-earthworm systems and implications for environmental risk assessment
    Mohd Firdaus MA, Agatz A, Hodson ME, Al-Khazrajy OSA, Boxall ABA
    Environ Toxicol Chem, 2018 05;37(5):1420-1429.
    PMID: 29341233 DOI: 10.1002/etc.4094
    Nanopesticides are novel plant protection products offering numerous benefits. Because nanoparticles behave differently from dissolved chemicals, the environmental risks of these materials could differ from conventional pesticides. We used soil-earthworm systems to compare the fate and uptake of analytical-grade bifenthrin to that of bifenthrin in traditional and nanoencapsulated formulations. Apparent sorption coefficients for bifenthrin were up to 3.8 times lower in the nano treatments than in the non-nano treatments, whereas dissipation half-lives of the nano treatments were up to 2 times longer. Earthworms in the nano treatments accumulated approximately 50% more bifenthrin than those in the non-nano treatments. In the non-nano treatments, most of the accumulated material was found in the earthworm tissue, whereas in the nano treatments, the majority resided in the gut. Evaluation of toxicokinetic modeling approaches showed that models incorporating the release rate of bifenthrin from the nanocapsule and distribution within the earthworm provided the best estimations of uptake from the nano-formulations. Overall, our findings indicate that the risks of nanopesticides may be different from those of conventional formulations. The modeling presented provides a starting point for assessing risks of these materials but needs to be further developed to better consider the behavior of the nanoencapsulated pesticide within the gut system. Environ Toxicol Chem 2018;37:1420-1429. © 2018 SETAC.
    Matched MeSH terms: Oligochaeta/metabolism*; Pesticides/metabolism*; Pyrethrins/metabolism
  16. Sonic Hedgehog Regulation of the Neural Precursor Cell Fate During Chicken Optic Tectum Development
    Yang C, Li X, Li Q, Li H, Qiao L, Guo Z, et al.
    J Mol Neurosci, 2018 Feb;64(2):287-299.
    PMID: 29285739 DOI: 10.1007/s12031-017-1019-5
    During nervous system development, neurons project axons over long distances to reach the appropriate targets for correct neural circuit formation. Sonic hedgehog (Shh) is a secreted protein and plays a key role in regulating vertebrate embryogenesis, especially in central nervous system (CNS) patterning, including neuronal migration and axonal projection in the brain and spinal cord. In the developing ventral midbrain, Shh is sufficient to specify a striped pattern of cell fates. Little is known about the molecular mechanisms underlying the Shh regulation of the neural precursor cell fate during the optic tectum development. Here, we aimed at studying how Shh might regulate chicken optic tectum patterning. In the present study, in ovo electroporation methods were employed to achieve the overexpression of Shh in the optic tectum during chicken embryo development. Besides, the study combined in ovo electroporation and neuron isolation culturing to study the function of Shh in vivo and in vitro. The fluorescent immunohistochemistry methods were used to check the related indicators. The results showed that Shh overexpression caused 87.8% of cells to be distributed to the stratum griseum central (SGC) layer, while only 39.3% of the GFP-transfected cells resided in the SGC layer in the control group. Shh overexpression also reduced the axon length in vivo and in vitro. In conclusion, we provide evidence that Shh regulates the neural precursor cell fate during chicken optic tectum development. Shh overexpression impairs neuronal migration and may affect the fate determination of transfected neurons.
    Matched MeSH terms: Superior Colliculi/metabolism*; Hedgehog Proteins/metabolism; Neural Stem Cells/metabolism*
  17. Fulltext Single-cell RNA sequencing analysis of shrimp immune cells identifies macrophage-like phagocytes
    Yang P, Chen Y, Huang Z, Xia H, Cheng L, Wu H, et al.
    Elife, 2022 Oct 06;11.
    PMID: 36200862 DOI: 10.7554/eLife.80127
    Despite the importance of innate immunity in invertebrates, the diversity and function of innate immune cells in invertebrates are largely unknown. Using single-cell RNA-seq, we identified prohemocytes, monocytic hemocytes, and granulocytes as the three major cell-types in the white shrimp hemolymph. Our results identified a novel macrophage-like subset called monocytic hemocytes 2 (MH2) defined by the expression of certain marker genes, including Nlrp3 and Casp1. This subtype of shrimp hemocytes is phagocytic and expresses markers that indicate some conservation with mammalian macrophages. Combined, our work resolves the heterogenicity of hemocytes in a very economically important aquatic species and identifies a novel innate immune cell subset that is likely a critical player in the immune responses of shrimp to threatening infectious diseases affecting this industry.
    Matched MeSH terms: Macrophages/metabolism; Phagocytes/metabolism; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism
  18. Fulltext Anti-pancreatic lipase and anti-adipogenic effects of 5, 7, 3',4',5' -pentamethoxy and 6, 2',4'-trimethoxy flavone - An In vitro study
    Ahmad B, Friar EP, Taylor E, Vohra MS, Serpell CJ, Garrett MD, et al.
    Eur J Pharmacol, 2023 Jan 05;938:175445.
    PMID: 36473593 DOI: 10.1016/j.ejphar.2022.175445
    In this study, the anti-obesity effects of 5,7,3',4',5-pentamethoxyflavone (PMF) and 6,2',4'-trimethoxyflavone (TMF) were evaluated through two distinct mechanisms of action: inhibition of crude porcine pancreatic lipase (PL), and inhibition of adipogenesis in 3T3-L1 pre-adipocytes. Both flavones show dose dependent, competitive inhibition of PL activity. Molecular docking studies revealed binding of the flavones to the active site of PL. In 3T3-L1 adipocytes, both flavones reduced the accumulation of lipids and triglycerides. PMF and TMF also lowered the expression of adipogenic and lipogenic genes. They both reduced the expression of peroxisome proliferator-activated receptor-gamma (PPAR-γ), CCAAT/enhancer-binding protein α and β (C/EBP α and β), sterol regulatory element-binding protein 1 (SREBF 1), fatty acid synthase (FASN), adipocyte binding protein 2 (aP2), and leptin gene. In addition, these flavones enhanced adiponectin mRNA expression, increased lipolysis and enhanced the expression of lipolytic genes: adipose triglycerides lipase (ATGL), hormone sensitive lipase (HSL) and monoglycerides lipase (MAGL) in mature 3T3-L1 adipocytes. Overall, PMF was seen to be a more potent inhibitor of both PL activity and adipogenesis versus TMF. These results suggest that PMF and TMF possess anti-obesity activities and can be further evaluated for their anti-obesity effects.
    Matched MeSH terms: Lipase/metabolism; Triglycerides/metabolism; PPAR gamma/metabolism
  19. Caffeine prevents restenosis and inhibits vascular smooth muscle cell proliferation through the induction of autophagy
    Tripathi M, Singh BK, Liehn EA, Lim SY, Tikno K, Castano-Mayan D, et al.
    Autophagy, 2022 Sep;18(9):2150-2160.
    PMID: 35012409 DOI: 10.1080/15548627.2021.2021494
    Caffeine is among the most highly consumed substances worldwide, and it has been associated with decreased cardiovascular risk. Although caffeine has been shown to inhibit the proliferation of vascular smooth muscle cells (VSMCs), the mechanism underlying this effect is unknown. Here, we demonstrated that caffeine decreased VSMC proliferation and induced macroautophagy/autophagy in an in vivo vascular injury model of restenosis. Furthermore, we studied the effects of caffeine in primary human and mouse aortic VSMCs and immortalized mouse aortic VSMCs. Caffeine decreased cell proliferation, and induced autophagy flux via inhibition of MTOR signaling in these cells. Genetic deletion of the key autophagy gene Atg5, and the Sqstm1/p62 gene encoding a receptor protein, showed that the anti-proliferative effect by caffeine was dependent upon autophagy. Interestingly, caffeine also decreased WNT-signaling and the expression of two WNT target genes, Axin2 and Ccnd1 (cyclin D1). This effect was mediated by autophagic degradation of a key member of the WNT signaling cascade, DVL2, by caffeine to decrease WNT signaling and cell proliferation. SQSTM1/p62, MAP1LC3B-II and DVL2 were also shown to interact with each other, and the overexpression of DVL2 counteracted the inhibition of cell proliferation by caffeine. Taken together, our in vivo and in vitro findings demonstrated that caffeine reduced VSMC proliferation by inhibiting WNT signaling via stimulation of autophagy, thus reducing the vascular restenosis. Our findings suggest that caffeine and other autophagy-inducing drugs may represent novel cardiovascular therapeutic tools to protect against restenosis after angioplasty and/or stent placement.
    Matched MeSH terms: Caffeine/metabolism; Myocytes, Smooth Muscle/metabolism; Sequestosome-1 Protein/metabolism
  20. Fulltext Evaluation of vasodilatory effect and antihypertensive effect of chrysin through in vitro and sub-chronic in vivo study
    Tew WY, Tan CS, Yan CS, Loh HW, Wen X, Wei X, et al.
    Biomed Pharmacother, 2023 Jan;157:114020.
    PMID: 36469968 DOI: 10.1016/j.biopha.2022.114020
    Chrysin, a bioflavonoid belonging to the flavone, occurs naturally in plants such as the passionflower, honey and propolis. Few studies have demonstrated that chrysin can promote vasorelaxant activities in rats' aorta and mesenteric arteries. To date, no research has explored the signalling system routes that chrysin may utilise to produce its vasorelaxant action. Therefore, this study aimed to investigate the underlying mechanisms involved in chrysin-induced vasorelaxant in rats' aortic rings and assess the antihypertensive effect of chrysin in spontaneously hypertensive rats (SHRs). The findings revealed that chrysin utilised both endothelium-dependent and endothelium-independent mechanisms. The presence of L-NAME (endothelial NO synthase inhibitor), ODQ (sGC inhibitor), methylene blue (cGMP lowering agent), 4-AP (voltage-gated potassium channel inhibitor), atropine (muscarinic receptors inhibitor) and propranolol (β-adrenergic receptors inhibitor) significantly reduced the chrysin's vasorelaxant action. Furthermore, chrysin can reduce intracellular Ca2+ levels by limiting the extracellular intake of Ca2+ through voltage-operated calcium channels and blocking the intracellular release of Ca2+ from the sarcoplasmic reticulum via the IP3 receptor. These indicate that chrysin-induced vasorelaxants involved NO/sGC/cGMP signalling cascade, muscarinic and β-adrenergic receptors, also the potassium and calcium channels. Although chrysin had vasorelaxant effects in in vitro studies, the in vivo antihypertensive experiment discovered chrysin does not significantly reduce the blood pressure of SHRs following 21 days of oral treatment. This study proved that chrysin utilised multiple signalling pathways to produce its vasorelaxant effect in the thoracic aorta of rats; however, it had no antihypertensive effect on SHRs.
    Matched MeSH terms: Cyclic GMP/metabolism; Receptors, Adrenergic, beta/metabolism; Calcium Channels/metabolism
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