Diabetes mellitus (DM) is a major health problem worldwide and it will rapidly increase. This disease is characterized by hyperglycemia caused by defects in insulin secretion, insulin action or both. DM has three types: T1DM, T2M and gestational DM (GDM), of them T2DM is more frequent. Multiple genes and their interactions are involved in insulin secretion pathway. Sulfonylurea receptor encoded by ABCC8 gene, together with inward-rectifier potassium ion channel (Kir6.2) regulates insulin secretion by ATP-sensitive K(+) (KATP) channel located in the plasma membranes. Disruption of these molecules by different mutations is responsible for risk of DM. Several single nucleotide polymorphisms (SNPs) of ABCC8 gene and their interaction are involved in pathogenicity of DM. This review summarizes the current evidence of contribution of ABC8 genetic variants to the development of DM.
Neuroinflammation is known as a key player in a variety of neurodegenerative and/or neurological diseases. Brain Toll-like receptors (TLRs) are leading elements in the initiation and progression of neuroinflammation and the development of different neuronal diseases. Furthermore, TLR activation is one of the most important elements in the induction of insulin resistance in different organs such as the central nervous system. Involvement of insulin signaling dysregulation and insulin resistance are also shown to contribute to the pathology of neurological diseases. Considering the important roles of TLRs in neuroinflammation and central insulin resistance and the effects of these processes in the initiation and progression of neurodegenerative and neurological diseases, here we are going to review current knowledge about the potential crosstalk between TLRs and insulin signaling pathways in neuroinflammatory disorders of the central nervous system.
Matched MeSH terms: Central Nervous System/metabolism*; Receptor, Insulin/metabolism*; Toll-Like Receptors/metabolism*
Near-real-ime assay is anassay method that the whole process from sampling until results could be obtained in approximately Iess than one hour. The ElIman assay for acetyl cholinesterase (AChE) has near real-time potential due to its simplicity and fast assay time. The commercial acetylcholinesterase from Electrophorus electricus is well known for its uses in insecticides detection. A lesser known fact is AChE is also sensitive to heavy metals. A near real-time inhibitive assay for heavy metals using AChE from this source showed promising results. Several heavy metals such as copper, silver and mercury could be etected with IC50 values of1.212, 0.1185 and 0.097 mg I-1, respectively. The Limits of Detection (LOD) for copper, silver and mercury were 0.01, 0.015 and 0.01 mg I-1, respectively. TheLimits of quantitation (LOQ) or copper, silver and mercury were 0.196, 0.112 and 0.025 mg I-1, respectively. The LOQvalues for copper, silver and mercury were well below the maximum permissible limit for these metal ions as outlined by Malaysian Department of Environment. A polluted location demonstrated near real-time applicability of the assay with variation oftemporal levels of heavy metals detected. The results show that AChE from Electrophorus electricus has the potential to be used as a near real-time biomonitoring tool for heavy
Ionic liquids (ILs) have been used as an alternative green solvent for lignocelluloses pretreatment. However, being a salt, ILs exhibit an inhibitory effect on cellulases activity, thus making the subsequent saccharification inefficient. The aim of the present study is to produce salt-tolerant cellulases, with the rationale that the enzyme also tolerant to the presence of ILs. The enzyme was produced from a locally isolated halophilic strain and was characterized and assessed for its tolerance to different types of ionic liquids. The results showed that halophilic cellulases produced from Aspergillus terreus UniMAP AA-6 exhibited higher tolerance to ILs and enhanced thermo stability in the presence of high saline conditions.
Schistosomiasis is a major parasitic disease of humans, second only to malaria in its global impact. The disease is caused by digenean trematodes that infest the vasculature of their human hosts. These flukes are limited externally by a body wall composed of a syncytial epithelium, the apical surface membrane of which is a parasitism-adapted dual membrane complex. Annexins are thought to be of integral importance for the stability of this apical membrane system. Here, we present the first structural and immunobiochemical characterization of an annexin from Schistosoma mansoni. The crystal structure of annexin B22 confirms the presence of the previously predicted α-helical segment in the II/III linker and reveals a covalently linked head-to-head dimer. From the calcium-bound crystal structure of this protein, canonical type II, type III and B site positions are occupied, and a novel binding site has been identified. The dimer arrangement observed in the crystal structure suggests the presence of two prominent features, a potential non-canonical membrane binding site and a potential binding groove opposite to the former. Results from transcriptional profiling during development show that annexin B22 expression is correlated with life stages of the parasite that possess the syncytial tegument layer, and ultrastructural localization by immuno-electron microscopy confirms the occurrence of annexins in the tegument of S. mansoni. Data from membrane binding and aggregation assays indicate the presence of differential molecular mechanisms and support the hypothesis of annexin B22 providing structural integrity in the tegument.
Nutritional or dietary factors have drawn attention due to their potential as an effective chemopreventive agent, which is considered a more rational strategy in cancer treatment. This study was designed to evaluate the effect of IP₆ extracted from rice bran on azoxymethane- (AOM-) induced colorectal cancer (CRC) in rats. Initially, male Sprague Dawley rats were divided into 5 groups, with 6 rats in each group. The rats received two intraperitoneal (i.p.) injections of AOM in saline (15 mg/kg body weight) over a 2-week period to induce CRC. IP₆ was given in three concentrations, 0.2% (w/v), 0.5% (w/v), and 1.0% (w/v), via drinking water for 16 weeks. The deregulation of the Wnt/β-catenin signaling pathway and the expression of cyclooxygenase (COX)-2 have been implicated in colorectal tumorigenesis. β-Catenin and COX-2 expressions were analysed using the quantitative RT-PCR and Western blotting. Herein, we reported that the administration of IP₆ markedly suppressed the incidence of tumors when compared to the control. Interestingly, the administration of IP₆ had also markedly decreased β-catenin and COX-2 in colon tumors. Thus, the downregulation of β-catenin and COX-2 could play a role in inhibiting the CRC development induced by IP₆ and thereby act as a potent anticancer agent.
The presence of phorbol esters (PEs) with toxic properties limits the use of Jatropha curcas kernel in the animal feed industry. Therefore, suitable methods to detoxify PEs have to be developed to render the material safe as a feed ingredient. In the present study, the biological treatment of the extracted PEs-rich fraction with non-pathogenic fungi (Trichoderma harzianum JQ350879.1, T. harzianum JQ517493.1, Paecilomyces sinensis JQ350881.1, Cladosporium cladosporioides JQ517491.1, Fusarium chlamydosporum JQ350882.1, F. chlamydosporum JQ517492.1 and F. chlamydosporum JQ350880.1) was conducted by fermentation in broth cultures. The PEs were detected by liquid chromatography-diode array detector-electrospray ionization mass spectrometry (LC-DAD-ESIMS) and quantitatively monitored by HPLC using phorbol-12-myristate 13-acetate as the standard. At day 30 of incubation, two T. harzianum spp., P. sinensis and C. cladosporioides significantly (p < 0.05) removed PEs with percentage losses of 96.9%-99.7%, while F. chlamydosporum strains showed percentage losses of 88.9%-92.2%. All fungal strains could utilize the PEs-rich fraction for growth. In the cytotoxicity assay, cell viabilities of Chang liver and NIH 3T3 fibroblast cell lines were less than 1% with the untreated PEs-rich fraction, but 84.3%-96.5% with the fungal treated PEs-rich fraction. There was no inhibition on cell viability for normal fungal growth supernatants. To conclude, Trichoderma spp., Paecilomyces sp. and Cladosporium sp. are potential microbes for the detoxification of PEs.
In this laboratory-scale study, earthworms were introduced as biodegraders of palm oil mill effluent (POME), which is a wastewater produced from the wet process of palm oil milling. POME was absorbed into amendments (soil or rice straw) in different ratios as feedstocks for the earthworm, Eudrilus eugeniae. The presence of earthworms led to significant increases in pH, electrical conductivity, and nutrient content but decreases in the C/N ratio (0.687-75.8%), soluble chemical oxygen demand (19.7-87.9%), and volatile solids (0.687-52.7%). However, earthworm growth was reduced in all treatments by the end of the treatment process. Rice straw was a better amendment/absorbent relative to soil, with a higher nutrient content and greater reduction in soluble chemical oxygen demand with a lower C/N ratio in the vermicompost. Among all treatments investigated, the treatment with 1 part rice straw and 3 parts POME (w/v) (RS1:3) produced the best quality vermicompost with high nutritional status.
Matched MeSH terms: Oligochaeta/metabolism*; Plant Oils/metabolism*; Water Pollutants, Chemical/metabolism*
In searching for symbionts derived from bioactive natural products, six sulfureous diketopiperazines designated as lasiodiplines A-F (1-6) were characterized from the culture of Lasiodiplodia pseudotheobromae F2, previously residing in the apparently normal flower of Illigera rhodantha (Hernandiaceae). Identification of structures was accomplished by a combination of spectroscopic and computational approaches, in conjunction with the low-temperature (100K) single-crystal X-ray diffraction with Cu Kα radiation. Lasiodipline E (5) was demonstrated to be antibacterial against the clinical strains Streptococcus sp., Bacteroides vulgates, Peptostreptococcus sp. and Veillonella parvula, respectively, with an minimum inhibitory concentration (MIC) range of 0.12-0.25 μg/mL. In addition, compounds 4 and 6 exemplify two unusual architectures of natural cyclodipeptides, signifying the unique biochemical characteristics of the producing fungus.
Major concern about the presence of fluoranthene, which consists of four fused benzene rings, in the environment has been raised in the past few years due to its toxic, mutagenic, and persistent organic pollutant properties. In this study, we investigated the removal of fluoranthene under static and agitated conditions. About 89% fluoranthene was removed within 30 days under the agitated condition, whereas under the static condition, only 54% fluoranthene was removed. We further investigated the behavior and mechanism of fluoranthene biosorption and biotransformation by Pleurotus eryngii F032 to accelerate the elimination of fluoranthene. The optimum conditions for the elimination of fluoranthene by P. eryngii F032 included a temperature of 35 °C, pH 3, 0.2% inoculum concentration, and a C/N ratio of 16. Under these conditions at the initial fluoranthene concentration of 10 mg/L, more than 95% of fluoranthene was successfully removed within 30 days. Of those factors influencing the biodegradation of fluoranthene, salinity, glucose, and rhamnolipid content were of the greatest importance. Degradation metabolites identified using gas chromatography-mass spectrometry were 1-naphthalenecarboxylic acid and salicylic acid, suggesting possible metabolic pathways. Finally, it can be presumed that the major mechanism of fluoranthene elimination by white-rot fungi is to mineralize polycyclic aromatic hydrocarbons via biotransformation enzymes like laccase.
This research was carried out to evaluate the effects of flavone, myricetin, naringin, catechin, rutin, quercetin, and kaempferol at the concentration of 4.5% of the substrate (dry matter basis) on the rumen microbial activity in vitro. Mixture of guinea grass and concentrate (60 : 40) was used as the substrate. The results showed that all the flavonoids except naringin and quercetin significantly (P < 0.05) decreased the dry matter degradability. The gas production significantly (P < 0.05) decreased by flavone, myricetin, and kaempferol, whereas naringin, rutin, and quercetin significantly (P < 0.05) increased the gas production. The flavonoids suppressed methane production significantly (P < 0.05). The total VFA concentration significantly (P < 0.05) decreased in the presence of flavone, myricetin, and kaempferol. All flavonoids except naringin and quercetin significantly (P < 0.05) reduced the carboxymethyl cellulase, filter paperase, xylanase, and β -glucosidase activities, purine content, and the efficiency of microbial protein synthesis. Flavone, myricetin, catechin, rutin, and kaempferol significantly (P < 0.05) reduced the population of rumen microbes. Total populations of protozoa and methanogens were significantly (P < 0.05) suppressed by naringin and quercetin. The results of this research demonstrated that naringin and quercetin at the concentration of 4.5% of the substrate (dry matter basis) were potential metabolites to suppress methane production without any negative effects on rumen microbial fermentation.
Oil palm is the most productive oil-bearing crop. Although it is planted on only 5% of the total world vegetable oil acreage, palm oil accounts for 33% of vegetable oil and 45% of edible oil worldwide, but increased cultivation competes with dwindling rainforest reserves. We report the 1.8-gigabase (Gb) genome sequence of the African oil palm Elaeis guineensis, the predominant source of worldwide oil production. A total of 1.535 Gb of assembled sequence and transcriptome data from 30 tissue types were used to predict at least 34,802 genes, including oil biosynthesis genes and homologues of WRINKLED1 (WRI1), and other transcriptional regulators, which are highly expressed in the kernel. We also report the draft sequence of the South American oil palm Elaeis oleifera, which has the same number of chromosomes (2n = 32) and produces fertile interspecific hybrids with E. guineensis but seems to have diverged in the New World. Segmental duplications of chromosome arms define the palaeotetraploid origin of palm trees. The oil palm sequence enables the discovery of genes for important traits as well as somaclonal epigenetic alterations that restrict the use of clones in commercial plantings, and should therefore help to achieve sustainability for biofuels and edible oils, reducing the rainforest footprint of this tropical plantation crop.
The effect of Leucaena leucocephala hybrid-Bahru (LLB), which contains a high concentration of condensed tannins, on cellulolytic rumen fungal population in goats was investigated using real-time PCR. The fungal population in goats fed LLB was inhibited during the first 10 days of feeding, but after 15 days of feeding, there was a tremendous increase of fungal population (157.0 μg/ml), which was about fourfold more than that in control goats (39.7 μg/ml). However, after this period, the fungal population decreased continuously, and at 30 days of feeding, the fungal population (50.6 μg/ml) was not significantly different from that in control goats (55.4 μg/ml).
Oligopeptidase B (OPB) is a member of the prolyl oligopeptidase (POP) family of serine proteases. OPB in trypanosomes is an important virulence factor and potential pharmaceutical target. Characteristic structural features of POP family members include lack of a propeptide and presence of a β-propeller domain (PD), although the role of the β-PD has yet to be fully understood. In this work, residues Glu(172), Glu(490), Glu(524) and Arg(689) in Trypanosoma brucei OPB (Tb OPB), which are predicted to form inter-domain salt bridges, were substituted for Gln and Ala, respectively. These mutants were evaluated in terms of catalytic properties and stability. A negative effect on kcat/Km was obtained following mutation of Glu(172) or Arg(689). In contrast, the E490Q mutant exhibited markedly decreased thermal stability, although this mutation had less effect on catalytic properties compared to the E172Q and R689A mutants. Trypsin digestion showed that the boundary regions between the β-PD and catalytic domains (CDs) of the E490Q mutant are unfolded with heat treatment. These results indicated that Glu(490) in the CD plays a role in stabilization of Tb OPB, whereas Glu(172) in the β-PD is critical for the catalytic activity of Tb OPB.
Developmental biochemical information is a vital base for the elucidation of seed physiology and metabolism. However, no data regarding the biochemical profile of oil palm (Elaeis guineensis Jacq.) seed development has been reported thus far. In this study, the biochemical changes in the developing oil palm seed were investigated to study their developmental pattern. The biochemical composition found in the seed differed significantly among the developmental stages. During early seed development, the water, hexose (glucose and fructose), calcium and manganese contents were present in significantly high levels compared to the late developmental stage. Remarkable changes in the biochemical composition were observed at 10 weeks after anthesis (WAA): the dry weight and sucrose content increased significantly, whereas the water content and hexose content declined. The switch from a high to low hexose/sucrose ratio could be used to identify the onset of the maturation phase. At the late stage, dramatic water loss occurred, whereas the content of storage reserves increased progressively. Lauric acid was the most abundant fatty acid found in oil palm seed starting from 10 WAA.
Precise uterine fluid pH regulation may involve the Na(+)/H(+)-exchanger (NHE). We hypothesized that NHE isoforms are differentially expressed under different sex steroid treatment and at different oestrous cycle phases which may explain the uterine fluid pH changes observed under these conditions.
Molecular dynamics (MD) simulations of membrane-embedded G-protein coupled receptors (GPCRs) have rapidly gained popularity among the molecular simulation community in recent years, a trend which has an obvious link to the tremendous pharmaceutical importance of this group of receptors and the increasing availability of crystal structures. In view of the widespread use of this technique, it is of fundamental importance to ensure the reliability and robustness of the methodologies so they yield valid results and enable sufficiently accurate predictions to be made. In this work, 200 ns simulations of the A2a adenosine receptor (A2a AR) have been produced and evaluated in the light of these requirements. The conformational dynamics of the target protein, as obtained from replicate simulations in both the presence and absence of an inverse agonist ligand (ZM241385), have been investigated and compared using principal component analysis (PCA). Results show that, on this time scale, convergence of the replicates is not readily evident and dependent on the types of the protein motions considered. Thus rates of inter- as opposed to intrahelical relaxation and sampling can be different. When studied individually, we find that helices III and IV have noticeably greater stability than helices I, II, V, VI, and VII in the apo form. The addition of the inverse agonist ligand greatly improves the stability of all helices.
Cytochromes P450 (CYPs) play a central role in the Phase I metabolism of drugs and other xenobiotics. It is estimated that CYPs can metabolize up to two-thirds of drugs present in humans. Over the past two decades, there have been numerous advances in in vitro methodologies to characterize drug metabolism and interaction involving CYPs.
In this study, bulrush (Scirpus grossus) was subjected to a 72 day phytotoxicity test to assess its ability to phytoremediate diesel contamination in simulated wastewater at different concentrations (0, 8700, 17,400 and 26,100mg/L). Diesel degradation by S. grossus was measured in terms of total petroleum hydrocarbon (TPH-D). The TPH-D concentration in the synthetic wastewater was determined with the liquid-liquid extraction method and gas chromatography. S. grossus was found to reduce TPH-D by 70.0 and 80.2% for concentrations of 8700 mg/L and 17,400mg/L, respectively. At a diesel concentration of 26,100mg/L, S. grossus died after 14 days. Additionally, the biomass of S. grossus plants was found to increase throughout the phytotoxicity test, confirming the ability of the plant to survive in water contaminated with diesel at rates of less than 17,400mg/L.
Matched MeSH terms: Hydrocarbons/metabolism; Water Pollutants, Chemical/metabolism; Cyperaceae/metabolism
Selective blockade of the serotonin 5-HT(2A) receptor is a useful therapeutic approach for a number of disorders, including schizophrenia, insomnia and ischaemic heart disease. A series of aporphines were docked into a homology model of the rat 5-HT(2A) receptor using AutoDock. Selected compounds with high in silico binding affinities were screened in vitro using radioligand-binding assays against rat serotonin (5-HT(1A) and 5-HT(2A)) and dopamine (D1 and D2) receptors. (R)-Roemerine and (±)-nuciferine were found to have high affinity for the 5-HT(2A) receptor (K(i) = 62 and 139 nM, respectively), with (R)-roemerine showing 20- to 400-fold selectivity for the 5-HT(2A) receptor over the 5-HT(1A), D1 and D2 receptors. Investigation into the ligand-receptor interactions suggested that the selectivity of (R)-roemerine is due to it having stronger H-bonding and dipole-dipole interactions with several of the key residues in the 5-HT(2A) receptor-binding site.