Objectives:Limosilactobacillus reuteri is a beneficial Lactobacillus widely used in foods and supplements to promote overall health.Some studies also suggest it supports skin health and prevents allergies and cardiova...Objectives:Limosilactobacillus reuteri is a beneficial Lactobacillus widely used in foods and supplements to promote overall health.Some studies also suggest it supports skin health and prevents allergies and cardiovascular disease.However,research on its skin-protective effects against photoaging has not been conducted.This study evaluated the potential of culture broths fromthree L.reuteri strains(DS0333,DS0384,and DS0385)to inhibit skin photoaging.Methods:To assess their anti-photoaging potential,the culture broths were examined for antioxidant capacity,melanin inhibition,and collagen synthesis promotion.Radical scavenging activity was tested using 2,2-diphenyl-1-picrylhydrazyl(DPPH)and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS)assays.The biosynthetic activity of melanin and associated protein markers involved in melanogenesis was examined in a B16F10 mouse melanoma model.Type I procollagen synthesis and matrix metalloproteinase-1(MMP-1)inhibition were evaluated in ultraviolet B(UVB)-damaged human dermal fibroblasts(HDFs).Results:The culture broths exhibited concentrationdependent antioxidant activity and significantly suppressed melanin synthesis triggered byα-melanocyte-stimulating hormone(α-MSH).Transcription factors involved inmelanogenesis,namelymicrophthalmia-associated transcription factor(MITF),tyrosinase-related protein 1(TRP-1),and 2(TRP-2),were significantly downregulated following treatment.Treatment with culture broths also enhanced type I procollagen production and inhibited MMP-1 activity and protein expression in UVB-exposed HDFs.Among the strains,DS0333 demonstrated the strongest efficacy and was further investigated.It enhanced the proliferation of skin cells and attenuated the levels of age-associated markers such as MMP-1,mitogen-activated protein kinase(MAPK),and activator protein 1(AP-1).High-performance liquid chromatography(HPLC)analysis identified phenyllactic acid(PLA)as the predominant active compound.Conclusions:These results indicate that DS0333 culture broth exhibits strong anti-aging effects and can be applied in functional cosmetics aimed at promoting skin health.展开更多
AIM:To investigate the efficacy of Eleutherine bulbosa(Mill.)Urb.bulb extract(EBE)on the 3D human retinoblastoma cancer cells(WERI-Rb-1)spheroids and explore its apoptotic mechanism.METHODS:The 3D WERI-Rb-1 and human ...AIM:To investigate the efficacy of Eleutherine bulbosa(Mill.)Urb.bulb extract(EBE)on the 3D human retinoblastoma cancer cells(WERI-Rb-1)spheroids and explore its apoptotic mechanism.METHODS:The 3D WERI-Rb-1 and human retinal pigmented epithelium cells(ARPE-19)spheroids were developed using type 1 murine collagen that was excised from the rat tail tendon and cultured via hanging drop and embedded techniques.The cytotoxic activity was examined by Alamar blue assay meanwhile,the morphological characteristics were assessed by 4’,6-diamidino-2-phenylindole(DAPI)and scanning electron microscopy(SEM).The mRNA and protein expressions of apoptotic and antioxidant signal transduction pathways were explored to ascertain its molecular mechanisms.The statistical analysis was carried out using GraphPad Prism.RESULTS:The Alamar blue assay portrayed higher half maximal inhibitory concentration(IC50)values of EBE and cisplatin on 3D WERI-Rb-1 model as compared to the previous study on 2D model.The results of DAPI and SEM illustrated apoptotic features upon treatment with EBE and cisplatin in a dose-dependent manner on 3D WERI-Rb-1 model.The mRNA and protein levels of apoptotic and antioxidant-related pathways were significantly affected by EBE and cisplatin,respectively(P<0.05).The regulation of gene and protein expressions of 3D WERI-Rb-1 spheroids differed from the 2D study,suggesting that the tumor microenvironment of extracellular matrix(ECM)collagen matrix hindered the EBE treatment efficacy,leading to apoptotic evasion.CONCLUSION:A significant inhibition effect of EBE is observed on the 3D WERI-Rb-1 spheroids.The presence of ECM causes an increase in cytotoxic resistance upon treatment with EBE and cisplatin.展开更多
Strategies for increasing rice yield are needed to keep pace with the expected global population growth and sustainably address the challenges posed by climate change.In Southeast Asian countries,rice farming benefits...Strategies for increasing rice yield are needed to keep pace with the expected global population growth and sustainably address the challenges posed by climate change.In Southeast Asian countries,rice farming benefits from the use of Azolla spp.for nitrogen supply.By virtue of their symbiosis with the nitrogen-fixing cyanobacterium Trichormus azollae,Azolla spp.are ferns that release nitrogen into the environment upon biomass decomposition.However,whether and to what extent actively growing Azolla plants influence the development of co-cultivated rice seedlings remains unclear.To address this,rice(Oryza sativa L.var.Kitaake)seedlings were co-cultivated hydroponically with Azolla filiculoides for up to two months.Morphological changes in rice roots and aerial organs were assessed alongside nitric oxide assays in rice roots,root transcriptomics,and targeted hormonomics of rice roots,leaves,and growth media.Here,we showed that co-cultivation with actively growing A.filiculoides alters rice root architecture by inducing a nitric oxide boost and accelerates leaf and tiller differentiation and proliferation.Overall,this study provides an in-depth analysis of the morphogenetic effects of co-cultivated A.filiculoides on rice during early vegetative growth.It also paves the way for studies assessing whether A.filiculoides co-cultivation primes rice plants to better withstand abiotic and biotic stresses.展开更多
AIM： To investigate alternative or subordinate pathways involved in colorectal tumorigenesis and tumor growth, possibly determining at-risk populations and predicting responses to treatment. METHODS： Using microarra...AIM： To investigate alternative or subordinate pathways involved in colorectal tumorigenesis and tumor growth, possibly determining at-risk populations and predicting responses to treatment. METHODS： Using microarray gene-expression analysis, we analyzed patterns of gene expression relative to canonical molecular changes and clinicopathological features in 84 sporadic colorectal cancer patients, standardized by tumor location. Subsets of differentially expressed genes were confirmed by real-time reverse-transcript polymerase chain reaction （RT-PCR）. RESULTS： The largest number of genes identified as being differentially expressed was by tumor location, and the next largest number by lymphovascular or neural invasion of tumor cells and by mismatch repair （NMR） defects. Amongst biological processes, the immune response was significantly implicated in entire molecular changes observed during colorectal tumorigenesis （P 〈 0.001）. Amongst 47 differentially expressed genes, seven （PISD, NIBP, BAI2, STOML1, MRPL21, MRPL16, and MKKS） were newly found to correlate with tumorigenesis and tumor growth. Most location-associated molecular changes had distinct effects on gene expression, but the effects of the latter were sometimes contradictory. CONCLUSION： We show that several differentially expressed genes were associated with canonical molecular changes in sporadic colorectal cancers, possibly constituting alternative or subordinate pathways of tumorigenesis. As tumor location was the dominant factor influencing differential gene expression, location-specific analysis may identify location-associated pathways and enhance the accuracy of class prediction.展开更多
AIM: To investigate p53 mutation and p21 expression in hepatocarcinogenesis induced by hepatitis B virus (HBV) and aflatoxin B1 (AFB1) in tree shrews, and to reveal the role of these genes in hepatocarcinogenesis.METH...AIM: To investigate p53 mutation and p21 expression in hepatocarcinogenesis induced by hepatitis B virus (HBV) and aflatoxin B1 (AFB1) in tree shrews, and to reveal the role of these genes in hepatocarcinogenesis.METHODS: Tree shrews were divided into four groups:group A, those infected with HBV and fed with AFB1 (n = 39);group B, those infected with HBV alone (n = 28); group C,those fed with AFB1 alone (n = 29); and group D, normal controls (n = 20). The tree shrews underwent liver biopsies once every 15 wk. Expression of p53 and p21 proteins and genes in the biopsies and tumor tissues of the experimental tree shrews was detected, respectively, by immunohistochemistry,and by Southem blotting and reverse transcription-polymerase chain reaction and sequencing.RESULTS: The incidence of hepatocellular carcinomas (HCC) was higher in group A (66.7%) than that in group B (3.57%) and C (30%). The time of HCC occurrence was also earlier in group A than that in group C (120.0±16.6 wk vs 153.3±5.8 wk, respectively, P<0.01). p53 protein was not detected by immunohistochemistry in all groups before the 75^th wk of the experiment. At the 105^th wk, the positive rates fo p53 were 78.6%, 60% and 71.4% in groups A, B and C, respectively, which were significantly higher than that in group D (10%) (all P<0.05). An abnormal band of p53 gene was observed in groups A and C. The mutation points of p53gene in tree shrews with HCC were at codons 275, 78 and 13. The nucleotide sequence and amino acid sequence of tree shrew's wild-type p53 showed 91.7% and 93.4% homologies with those of human p53,respectively. The immunopositivity for p21 was found before HCC development. The incidence of HCC was significantly higher in tree shrews that were positive for p21 than those negative for p21 (80.0% vs 11.0%, P<0.001).The incidence of HCC in p21 positive animals in group A was significantly higher than those positive for p21 in group C (P<O.05).CONCLUSION: A remarkable synergistic effect on HCC development exists between HBV and AFB1. p53 mutation promotes the development of HCC. HBV and AFB1 may synergistically induce p53 gene mutation, and stimulate ras gene expression, ras gene is activated at the earlier stage during hepatocarcinogenesis, p21 protein may be an early marker, and the alterations of p53 may be a late event in the development of HCC.展开更多
AIM:To investigate the role of hepatitis B virus X-protein(HBx)-induced reactive oxygen species(ROS)on liver carcinogenesis in HBx transgenic mice and HepG2-HBx cells.METHODS:Cell growth rate was analyzed,and through ...AIM:To investigate the role of hepatitis B virus X-protein(HBx)-induced reactive oxygen species(ROS)on liver carcinogenesis in HBx transgenic mice and HepG2-HBx cells.METHODS:Cell growth rate was analyzed,and through western blotting,mitogenic signaling was observed.Endogenous ROS from wild and HBx transgenic mice and HepG2-Mock and HBx cells were assayed by FACS-calibur.Identification of oxidized and reduced phosphatase and tensin homolog(PTEN)was analyzed through N-ethylmaleimide alkylation,nonreducing electrophoresis.RESULTS:We observed that the cell-proliferation-related phosphoinositide 3-kinase/Akt pathway is activated by HBx in vivo and in vitro.Increased ROS were detected by HBx.Tumor suppressor PTEN,via dephosphorylation of Akt,was oxidized and inactivated by increased ROS.Increased oxidized PTEN activated the mitogenic pathway through over-activated Akt.However,treatment with ROS scavenger N-acetyl cysteine can reverse PTEN to a reduced form.Endogenously produced ROS also stimulated HBx expression.CONCLUSION:HBx induced ROS promoted Akt pathways via oxidized inactive PTEN.HBx and ROS maintained a positive regulatory loop,which aggravated carcinogenesis.展开更多
Previous studies have demonstrated the possible role of several aquaporins in seed germination. But systematic investigation of the role ofaquaporin family members in this process is lacking. Here, the developmental r...Previous studies have demonstrated the possible role of several aquaporins in seed germination. But systematic investigation of the role ofaquaporin family members in this process is lacking. Here, the developmental regulation of plasma membrane intrinsic protein （PIP） expression throughout germination and post-germination processes in rice embryos was analyzed. The expression patterns of the PIPs suggest these aquaporins play different roles in seed germination and seedling growth. Partial silencing of the water channel genes, OsPIP1;1 and OsPIP1：3, reduced seed germination while over-expression of OsPIP1：3 promoted seed germination under water-stress conditions. Moreover, spatial expression analysis indicates that OsPIP1：3 is expressed predominantly in embryo during seed germination. Our data also revealed that the nitric oxide （NO） donors, sodium nitroprusside （SNP） and S-nitrosoglutathione （GSNO）, promoted seed germination; furthermore, the NO scavenger, 2-（4-carboxyphenyl）-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, inhibited germination and reduced the stimulative effects of SNP and GSNO on rice germination. Exogenous NO stimulated the transcription of OsPIP1：1, OsPIP1：2, OsPIP1：3 and OsPIP2：8 in germinating seeds. These results suggest that water channels play an important role in seed germination, acting, at least partly, in response to the NO signaling pathway.展开更多
Gastric cancer is a complex disease that is affected by multiple genetic and environmental factors. For the precise diagnosis and effective treatment of gastric cancer, the heterogeneity of the disease must be simplif...Gastric cancer is a complex disease that is affected by multiple genetic and environmental factors. For the precise diagnosis and effective treatment of gastric cancer, the heterogeneity of the disease must be simplified; one way to achieve this is by dividing the disease into subgroups. Toward this effort, recent advances in high-throughput sequencing technology have revealed four molecular subtypes of gastric cancer, which are classified as Epstein-Barr viruspositive, microsatellite instability, genomically stable, and chromosomal instability subtypes. We anticipate that this molecular subtyping will help to extend our knowledge for basic research purposes and will be valuable for clinical use. Here, we review the genomic and epigenomic heterogeneity of the four molecular subtypes of gastric cancer. We also describe a mutational meta-analysis and a reanalysis of DNA methylation that were performed using previously reported gastric cancer datasets.展开更多
Background:Increasing understanding on the functions of amino acids (AA) has led to new commercial applications and expansion of the worldwide markets.However,the current technologies rely heavily on non-food grade mi...Background:Increasing understanding on the functions of amino acids (AA) has led to new commercial applications and expansion of the worldwide markets.However,the current technologies rely heavily on non-food grade microorganism and chemical synthesis for the production of AA.Several studies reported that lactic acid bacteria (LAB) have the capability of producing AA owing to their well-established proteolytic system and amino acid biosynthesis genes.Hence,the objectives of this study were to explore the extracellular proteolytic activity of LAB isolated from various Malaysian fermented foods and their potential to produce AA extracellularly as feed supplements.Results:All the studied LAB isolates were versatile extracellular protease producers,whereby extracellular protease activities were detected from acidic to alkaline pH (pH 5,pH 6.5,pH 8) using qualitative and quantitative proteolytic assays.The highest proteolytic activity at pH 5 (15.76 U/mg) and pH 8 (19.42 U/mg) was achieved by Lactobacillus plantarum RG14,while Lactobacillus plantarum RS5 exhibited the highest proteolytic activity of 17.22 U/mg at pH 6.5.As for the results of AA production conducted in de Man,Rogosa and Sharpe medium and analysed by high pressure liquid chromatography system,all LAB isolates were capable of producing an array of AA.Generally,Pediococcus sp.showed greater ability for AA production as compared to Lactobacillus sp.Moreover,the studied LAB were able to produce a few major feed supplement AA such as methionine,lysine,threonine and tryptophan.P.pentosaceus TL-3 recorded the highest methionine and threonine productivity of 3.72 mg/L/h and 5.58 mg/L/h respectively.However,L.plantarum I-UL4 demonstrated a lysine productivity of 1.24 mg/L/h,while P.acidilactici TP-6 achieved up to 1.73 mg/L/h of tryptophan productivity.Conclusion:All the 17 studied LAB isolates possessed versatile extracellular proteolytic system and have vast capability of producing various amino acids including a few major feed supplement AA such as methionine,lysine,threonine and tryptophan.Despite AA production was strain dependent,the studied LAB isolates possessed vast potential and can be exploited further as a bio-agent or an alternative amino acids and bioactive peptide producers.展开更多
BACKGROUND Genomic profiling of tumors has contributed to the understanding of colorectal cancer(CRC), facilitating diagnosis, prognosis and selection of treatments,including targeted regimens. A report suggested that...BACKGROUND Genomic profiling of tumors has contributed to the understanding of colorectal cancer(CRC), facilitating diagnosis, prognosis and selection of treatments,including targeted regimens. A report suggested that a 19-gene-based risk classifier(TCA19) was a prognostic tool for patients with stage III CRC. The survival outcomes in patients with stage IV CRC are still poor and appropriate selection of targeted therapies and immunotherapies is challenging.AIM To assess clinical implication of TCA19 in patients with stage IV CRC, and to identify TCA19 with involvement in immune-oncology.METHODS A retrospective review of the medical records of 60 patients with stage IV CRC was conducted, assessing clinicopathological variables and progression-free survival(PFS). TCA19 gene expression was determined by quantitative polymerase chain reaction(qPCR) in matched normal and tumor tissues taken from the study cohort. Expression of potential immune-oncology regulatory proteins and targets was examined by immunohistochemistry(IHC), western blot, immunofluorescence staining in tissues from a validation cohort of 10 patients, and in CRC cell lines co-cultured with monocyte in vitro.RESULTS In the patients with TCA19 score higher than the median, the PFS rates of eight patients who received the targeted regimens were significantly higher than the PFS rates of four patients who received 5-fluorouracil-based regimen(P = 0.041).In multivariate analysis, expression of signaling lymphocytic activation molecule family, member 7(SLAMF7) and triggering receptor expressed on myeloid cells 1(TREM1) was associated with PFS in the 60-patient cohort. After checking another 10 validate set, the expression of the IHC, the level of real-time qPCR,and the level of western blot were lower for SLAMF7 and higher for TREM7 in primary and metastatic tumors than in normal tissues. In CRC cells expressing SLAMF7 that were co-cultured with a monocytic cell line, levels of CD 68 and CD73 were significantly lower at day 5 of co-culture than at day 0.CONCLUSION The TCA19 score might be prognostic for target-regimen-specific PFS in stage IV CRC. Down-regulation of SLAMF7 and up-regulation of TREM1 occur in primary and metastatic tumor tissues.展开更多
AIM: Irritable bowel syndrome (IBS) is a functional bowel disorder. Its major symptom is bowel dysmotility, yet the mechanism of the symptom is poorly understood. Since the neurokinin-1 receptor (NK1R)-mediated signal...AIM: Irritable bowel syndrome (IBS) is a functional bowel disorder. Its major symptom is bowel dysmotility, yet the mechanism of the symptom is poorly understood. Since the neurokinin-1 receptor (NK1R)-mediated signaling in the gut is important in the control of normal bowel motor function,we aimed to investigate whether the NK1R-mediated bowel motor function was altered in IBS, using a rat IBS model that was previously reported to show colonic dysmotility in response to restraint stress.METHODS: IBS symptoms were produced in male SpragueDawley rats by inducing colitis with acetic acid. Rats were left to recover from colitis for 6 d, and used for experiments 7 d post-induction of colitis. Motor activities of distal colon were recorded in vitro.RESULTS: The contractile sensitivity of isolated colon to a NK1R agonist [Sar9, Met(O2)11]-substance P (1-30 nmol/L)was higher in IBS rats than that in normal rats. After the enteric neurotransmission was blocked by tetrodotoxin (TTX, 1 μmol/L), the contractile sensitivity to the NK1R agonist was increased in normal colon but not in IBS rat colon. The NK1R agonist-induced contraction was not different between the two groups when the agonist was challenged to the TTX-treated colon or the isolated colonic myocytes. A nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 100 μmol/L) augmented the NK1R agonist-induced contraction only in normal rat colon.CONCLUSION: These results suggest that the NK1R-meidated colonic motor response is increased in IBS rats, due to the decrease in the nitrergic inhibitory neural component.展开更多
Objective: To compare the in vitro antioxidant capacity of a diatom, Chaetoceros calcitrans(C. calcitrans) extracted using six types of solvents.Methods: Each extract was evaluated in terms of extraction yield, total ...Objective: To compare the in vitro antioxidant capacity of a diatom, Chaetoceros calcitrans(C. calcitrans) extracted using six types of solvents.Methods: Each extract was evaluated in terms of extraction yield, total carotenoid,fucoxanthin content, total phenolic and antioxidant capacities(DPPH and ABTS +scavenging activity and iron chelating activity).Results: The methanol extract exhibited the highest yield [(22.71 ± 0.96) g/100 g dry weight(DW)], total carotenoid [(4.46 ± 0.36) mg/g DW], total phenolic [(2.49 ± 0.08) mg gallic acid equivalents/g DW] and second highest fucoxanthin content [(2.08 ± 0.03) mg fucoxanthin/g DW] as compared to other solvent extracts. Methanolic extract also exhibited significantly higher(P < 0.05) scavenging(DPPH, ABTS +) and iron chelating activities.Conclusions: Methanol was the recommended solvent for the production of antioxidant rich extract from C. calcitrans. Both carotenoids and phenolic acids were found to be positively correlated to the antioxidant capacities of C. calcitrans. Lead bioactives confirmed by subsequent high performance liquid chromatography studies were fucoxanthin, gallic acid and protocatechuic acid.展开更多
Altitude and environmental variables such as edaphic properties are considered determinants of species distribution and community composition in mountain ecosystems.Here,we aimed to outline the effects of distinct mou...Altitude and environmental variables such as edaphic properties are considered determinants of species distribution and community composition in mountain ecosystems.Here,we aimed to outline the effects of distinct mountain peaks,altitude and soil properties on community composition,species density,phylogenetic structure and diversity of angiosperm páramo communities from the Serra do Brigadeiro State Park,Minas Gerais,southeastern Brazil.For that,we identified all angiosperm species found in 300 plots(1 m×1 m)from three mountain peaks,measured soil depth and analyzed soil fertility and texture in each plot.To reduce the number of soil variables and species composition,we computed principal coordinates based on soil properties and principal coordinates based on species-plot matrix for each plot.Furthermore,we computed the standard effect sizes of the mean phylogenetic pairwise distance and the mean nearest phylogenetic taxon distance for each plot to investigate differences in the degree of relatedness among coexisting species.We compared differences in response variables between peaks and modelled them in function of altitude and principle components of soil properties using mixed effect models.Species density and phylogenetic diversity differed between peaks,but,contrary to the previous findings,no relationships between species richness or phylogenetic diversity and altitude or soil properties were found,indicating that further investigations are necessary to understand the altitude-biodiversity relationship in Brazilian páramo vegetation.Community composition differed between peaks and depended on altitude,soil properties and interactions between them,indicating that upward shifting of bioclimatic conditions due to climate changes may alter communities of this ecosystem.Phylogenetic structure differed between peaks and was influenced by altitude and soil properties.As phylogenetic clustering increased with altitude,eventual upward movements of species in Brazilian páramo vegetation due to climate change may alter community composition and the degree of relatedness among coexisting species,increasing the risk of species from higher altitudes to disappear.Therefore,conservation priorities arise for higher landscape portions,where these high altitude species may find refuges.展开更多
The present study used in vitro and in silico techniques, as well as the metabolomics approach to characterise α-glucosidase inhibitors from different fractions of Clinacanthus nutans. C. nutans is a medicinal plant ...The present study used in vitro and in silico techniques, as well as the metabolomics approach to characterise α-glucosidase inhibitors from different fractions of Clinacanthus nutans. C. nutans is a medicinal plant belonging to the Acanthaceae family, and is traditionally used to treat diabetes in Malaysia. nHexane, n-hexane: ethyl acetate(1:1, v/v), ethyl acetate, ethyl acetate: methanol(1:1, v/v), and methanol fractions were obtained via partitioning of the 80% methanolic crude extract. The in vitro α-glucosidase inhibitory activity was analyzed using all the fractions collected, followed by profiling of the metabolites using liquid chromatography combined with mass spectrometry. The partial least square(PLS) statistical model was developed using the SIMCA P^+14.0 software and the following four inhibitors were obtained:(1) 4,6,8-Megastigmatrien-3-one;(2) N-Isobutyl-2-nonen-6,8-diynamide;(3) 1′,2′-bis(acetyloxy)-3′,4′-didehydro-2′-hydro-β, ψ-carotene; and(4) 22-acetate-3-hydroxy-21-(6-methyl-2,4-octadienoate)-olean-12-en-28-oic acid. The in silico study performed via molecular docking with the crystal structure of yeast isomaltase(PDB code: 3 A4 A) involved a hydrogen bond and some hydrophobic interactions between the inhibitors and protein. The residues that interacted include ASN259, HID295, LYS156, ARG335,and GLY209 with a hydrogen bond, while TRP15, TYR158, VAL232, HIE280, ALA292, PRO312, LEU313,VAL313, PHE314, ARG315, TYR316, VAL319, and TRP343 with other forms of bonding.展开更多
This study represents a well-dispersed gold nanoparticles(AuNPs)synthesis process via cellulose nanocrystals(CNC)which acts as both reducing and supporting agent.The synthesis process was ultrafast and completed in a ...This study represents a well-dispersed gold nanoparticles(AuNPs)synthesis process via cellulose nanocrystals(CNC)which acts as both reducing and supporting agent.The synthesis process was ultrafast and completed in a few seconds using microwave irradiation.The entire synthesis process was cost-effective,sustainable and eco-friendly.The synthesized(AuNPs/CNC)nanocomposite was investigated by transmission electron microscopy,selected area electron diffraction,Fourier transform infrared spectroscopy,energy dispersive X-ray analysis,X-ray diffraction,and UV–vis spectroscopy.The obtained AuNPs were well accumulated on the CNC surface and had a uniform spherical shape with an average diameter of 8±5.3 nm.The diameter of AuNPs could be altered by tuning the concentration of CNC suspension.The synthesized AuNPs/CNC nanocomposite film exhibited excellent degradation properties against various organic dyes,namely,Allura red,Congo red,Rhodamine B and Amaranth.The ultrafast degradation reactions followed pseudo first order kinetics.In the catalytic degradation reaction,AuNPs/CNC was transmitting electrons from a donor(NaBH4)to an acceptor(a dye).展开更多
In this study,we tried to verify the neuroprotective effect of Chrysanthemum indicum Linne(CIL)extract,which has been used as a botanical drug in East Asia,against ischemic damage and to explore the underlying mechani...In this study,we tried to verify the neuroprotective effect of Chrysanthemum indicum Linne(CIL)extract,which has been used as a botanical drug in East Asia,against ischemic damage and to explore the underlying mechanism involving the anti-inflammatory approach.A gerbil was given CIL extract for 7 consecutive days followed by bilateral carotid artery occlusion to make a cerebral ischemia/reperfusion model.Then,we found that CIL extracts protected pyramidal neurons in the hippocampal CA1 region(CA1)from ischemic damage using neuronal nucleus immunohistochemistry and Fluoro-Jade B histofluorescence.Accordingly,interleukin-13 immunoreactivities in the CA1 pyramidal neurons of CIL-pretreated animals were maintained or increased after cerebral ischemia/reperfusion.These findings indicate that the pre-treatment of CIL can attenuate neuronal damage/death in the brain after cerebral ischemia/reperfusion via an anti-inflammatory approach.展开更多
Chikungunya fever is a vector-borne viral disease transmitted to humans by chikungunya virus(CHIKV)-infected mosquitoes.There have been many outbreaks of CHIKV infection worldwide,and the virus poses ongoing risks to ...Chikungunya fever is a vector-borne viral disease transmitted to humans by chikungunya virus(CHIKV)-infected mosquitoes.There have been many outbreaks of CHIKV infection worldwide,and the virus poses ongoing risks to global health.To prevent and control CHIKV infection,it is important to improve the current CHIKV diagnostic approaches to allow for the detection of low CHIKV concentrations and to correctly distinguish CHIKV infections from those due to other mosquito-transmitted viruses,including dengue virus(DENV),Japanese encephalitis virus(JEV),and Zika virus(ZIKV).Here,we produced monoclonal antibodies(mAbs)against the CHIKV envelope 2 protein(CHIKV-E2)and compared their sensitivity and specificity with commercially available mAbs using enzyme-linked immunosorbent assays(ELISA).Two anti-CHIKV-E2 mAbs,19-1 and 21-1,showed higher binding affinities to CHIKV-E2 protein than the commercial mAbs did.In particular,the 19-1 mAb had the strongest binding affinity to inactivated CHIKV.Moreover,the 19-1 mAb had very little cross-reactivity with other mosquito-borne viruses,such as ZIKV,JEV,and DENV.These results suggest that the newly produced anti-CHIKV-E2 mAb,19-1,could he used for CHIKV diagnostic approaches.展开更多
Clusterin, a protein associated with multiple functions, is expressed in a wide variety of mammalian tissues. Although clusterin is known to be involved in neurodegenerative diseases, ageing, and tumorigenesis, a deta...Clusterin, a protein associated with multiple functions, is expressed in a wide variety of mammalian tissues. Although clusterin is known to be involved in neurodegenerative diseases, ageing, and tumorigenesis, a detailed analysis of the consequences of gain- or loss-of- function approaches has yet to be performed to understand the underlying mechanisms of clusterin functions. Since clusterin levels change in neurological diseases, it is likely that clusterin contributes to cell death and degeneration in general. Zebrafish was investigated as a model system to study human diseases. During development, zebrafish clusterin was expressed in the notochord and nervous system. Embryonic overexpression of clusterin by mRNA microinjection did not affect axis formation, whereas its knock-down by anti-sense morpholino treatment resulted in neuronal cell death. To analyze the function of clusterin in neurodegeneration, a transgenic zebrafish was investigated, in which nitroreductase expression is regulated under the control of a neuron-specifc huC promoter which is active between the stages of early neuronal precursors and mature neurons. Nitroreductase turns metronidazole into a cytotoxic agent that induces cell death within 12 h. After metronidazole treatment, transgenic zebrafish showed neuron-specific cell death. Interestingly, we also observed a dramatic induction of clusterin expression in the brain and spinal cord in these fish, suggesting a direct or indirect role of clusterin in neuronal cell death and thus, more generally, in neurodegeneration.展开更多
Dietary polyunsaturated fatty acids （PUFAs）, which are abundant in marine fish oils, have recently received global attention for their prominent anti-obesogenic effects. Among PUFAs, eicosapentaenoic acid （EPA; 20...Dietary polyunsaturated fatty acids （PUFAs）, which are abundant in marine fish oils, have recently received global attention for their prominent anti-obesogenic effects. Among PUFAs, eicosapentaenoic acid （EPA; 20：5n-3） and docosahexaenoic acid （DHA; 22：6n-3）, which are n-3 long-chain PUFAs widely referred to as omega-3 oils, were reported to prevent the development of obesity in rodents and humans. In the present study, we evaluated the anti-obesity effects of microalgal oil on high-fat induced obese C57BL/6 mice, compared with commercial omega-3 fish oil and vegetable corn oil. Microalgal oil is an inherent mixture of several PUFAs, including EPA, DHA and other fatty acids produced from a marine microalgal strain of Thraustochytriidae sp. derived mutant. It was found to contain more PUFAs （〉80%） and more omega-3 oils than commercial omega-3 fish oil （PUFAs 〉31%） and corn oil （PUFAs 59%）. All three types of oils induced weight loss in high-fat-induced obese mice, with the loss induced by microalgal oil being most significant at 9 weeks （10% reduction）. However, the oils tested did not improve blood lipid levels, although microalgal oil showed an apparent inhibitory effect on lipid accumulation in the liver. These findings may be attributed to the higher PUFA content, including omega-3 oils of microalgal oil than other oils. Collectively, these findings suggest that microalgal oil, derived from Thraustochytriidae sp. derived mutant, is a prominent candidate for replacement of omega-3 fish oils based on its apparent anti-obesity effect in vivo.展开更多
基金supported by a Korea Innovation Foundation(INNOPOLIS)grant funded by the Korean government(Ministry of Science and ICT)through a science and technology project that opens the future of the region(grant number:2021-DD-UP-0380).
文摘Objectives:Limosilactobacillus reuteri is a beneficial Lactobacillus widely used in foods and supplements to promote overall health.Some studies also suggest it supports skin health and prevents allergies and cardiovascular disease.However,research on its skin-protective effects against photoaging has not been conducted.This study evaluated the potential of culture broths fromthree L.reuteri strains(DS0333,DS0384,and DS0385)to inhibit skin photoaging.Methods:To assess their anti-photoaging potential,the culture broths were examined for antioxidant capacity,melanin inhibition,and collagen synthesis promotion.Radical scavenging activity was tested using 2,2-diphenyl-1-picrylhydrazyl(DPPH)and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS)assays.The biosynthetic activity of melanin and associated protein markers involved in melanogenesis was examined in a B16F10 mouse melanoma model.Type I procollagen synthesis and matrix metalloproteinase-1(MMP-1)inhibition were evaluated in ultraviolet B(UVB)-damaged human dermal fibroblasts(HDFs).Results:The culture broths exhibited concentrationdependent antioxidant activity and significantly suppressed melanin synthesis triggered byα-melanocyte-stimulating hormone(α-MSH).Transcription factors involved inmelanogenesis,namelymicrophthalmia-associated transcription factor(MITF),tyrosinase-related protein 1(TRP-1),and 2(TRP-2),were significantly downregulated following treatment.Treatment with culture broths also enhanced type I procollagen production and inhibited MMP-1 activity and protein expression in UVB-exposed HDFs.Among the strains,DS0333 demonstrated the strongest efficacy and was further investigated.It enhanced the proliferation of skin cells and attenuated the levels of age-associated markers such as MMP-1,mitogen-activated protein kinase(MAPK),and activator protein 1(AP-1).High-performance liquid chromatography(HPLC)analysis identified phenyllactic acid(PLA)as the predominant active compound.Conclusions:These results indicate that DS0333 culture broth exhibits strong anti-aging effects and can be applied in functional cosmetics aimed at promoting skin health.
基金Supported by Universiti Putra Malaysia,Serdang,Selangor,Malaysia(UPM/700-2/1/GPB/2017/9549900).
文摘AIM:To investigate the efficacy of Eleutherine bulbosa(Mill.)Urb.bulb extract(EBE)on the 3D human retinoblastoma cancer cells(WERI-Rb-1)spheroids and explore its apoptotic mechanism.METHODS:The 3D WERI-Rb-1 and human retinal pigmented epithelium cells(ARPE-19)spheroids were developed using type 1 murine collagen that was excised from the rat tail tendon and cultured via hanging drop and embedded techniques.The cytotoxic activity was examined by Alamar blue assay meanwhile,the morphological characteristics were assessed by 4’,6-diamidino-2-phenylindole(DAPI)and scanning electron microscopy(SEM).The mRNA and protein expressions of apoptotic and antioxidant signal transduction pathways were explored to ascertain its molecular mechanisms.The statistical analysis was carried out using GraphPad Prism.RESULTS:The Alamar blue assay portrayed higher half maximal inhibitory concentration(IC50)values of EBE and cisplatin on 3D WERI-Rb-1 model as compared to the previous study on 2D model.The results of DAPI and SEM illustrated apoptotic features upon treatment with EBE and cisplatin in a dose-dependent manner on 3D WERI-Rb-1 model.The mRNA and protein levels of apoptotic and antioxidant-related pathways were significantly affected by EBE and cisplatin,respectively(P<0.05).The regulation of gene and protein expressions of 3D WERI-Rb-1 spheroids differed from the 2D study,suggesting that the tumor microenvironment of extracellular matrix(ECM)collagen matrix hindered the EBE treatment efficacy,leading to apoptotic evasion.CONCLUSION:A significant inhibition effect of EBE is observed on the 3D WERI-Rb-1 spheroids.The presence of ECM causes an increase in cytotoxic resistance upon treatment with EBE and cisplatin.
基金carried out within the PRIN project 2017 (Prot.2017N5LBZK): A multidisciplinary approach to gain sustainable improvement of rice productivity through the co-cultivation with the fern Azolla and its cyanobacterial symbiont financed by the Italian Ministry of Research (MUR), the Agritech National Research Center that received funding from the European Union Next-Generation EU (PIANO NAZIONALE DI RIPRESA E RESILIENZA (PNRR) – MISSIONE 4 COMPONENTE 2, INVESTIMENTO 1.4 – D.D. 1032 17/06/2022, CN00000022)within the Tow Ards Next GENeration Crops Project, reg. no. CZ.02.01.01/00/22_008/0004581 of the ERDF program Johannes Amos Comeniusfunded by ‘ON Foods’ - Research and innovation network on food and nutrition Sustainability, Safety and Security – Working ON Foods B83C22004790001 PE_00000003 project.
文摘Strategies for increasing rice yield are needed to keep pace with the expected global population growth and sustainably address the challenges posed by climate change.In Southeast Asian countries,rice farming benefits from the use of Azolla spp.for nitrogen supply.By virtue of their symbiosis with the nitrogen-fixing cyanobacterium Trichormus azollae,Azolla spp.are ferns that release nitrogen into the environment upon biomass decomposition.However,whether and to what extent actively growing Azolla plants influence the development of co-cultivated rice seedlings remains unclear.To address this,rice(Oryza sativa L.var.Kitaake)seedlings were co-cultivated hydroponically with Azolla filiculoides for up to two months.Morphological changes in rice roots and aerial organs were assessed alongside nitric oxide assays in rice roots,root transcriptomics,and targeted hormonomics of rice roots,leaves,and growth media.Here,we showed that co-cultivation with actively growing A.filiculoides alters rice root architecture by inducing a nitric oxide boost and accelerates leaf and tiller differentiation and proliferation.Overall,this study provides an in-depth analysis of the morphogenetic effects of co-cultivated A.filiculoides on rice during early vegetative growth.It also paves the way for studies assessing whether A.filiculoides co-cultivation primes rice plants to better withstand abiotic and biotic stresses.
基金Supported by The Basic Research Program of the Korea Science & Engineering Foundation,No.R01-2006-000-10021-0the Korea Health 21 R&D Project,Ministry of Health & Welfare No.A062254
文摘AIM： To investigate alternative or subordinate pathways involved in colorectal tumorigenesis and tumor growth, possibly determining at-risk populations and predicting responses to treatment. METHODS： Using microarray gene-expression analysis, we analyzed patterns of gene expression relative to canonical molecular changes and clinicopathological features in 84 sporadic colorectal cancer patients, standardized by tumor location. Subsets of differentially expressed genes were confirmed by real-time reverse-transcript polymerase chain reaction （RT-PCR）. RESULTS： The largest number of genes identified as being differentially expressed was by tumor location, and the next largest number by lymphovascular or neural invasion of tumor cells and by mismatch repair （NMR） defects. Amongst biological processes, the immune response was significantly implicated in entire molecular changes observed during colorectal tumorigenesis （P 〈 0.001）. Amongst 47 differentially expressed genes, seven （PISD, NIBP, BAI2, STOML1, MRPL21, MRPL16, and MKKS） were newly found to correlate with tumorigenesis and tumor growth. Most location-associated molecular changes had distinct effects on gene expression, but the effects of the latter were sometimes contradictory. CONCLUSION： We show that several differentially expressed genes were associated with canonical molecular changes in sporadic colorectal cancers, possibly constituting alternative or subordinate pathways of tumorigenesis. As tumor location was the dominant factor influencing differential gene expression, location-specific analysis may identify location-associated pathways and enhance the accuracy of class prediction.
基金Supported by the National Natural Science Foundation of China,No.39260033Natural Science Foundation of Guangxi,No.0143058
文摘AIM: To investigate p53 mutation and p21 expression in hepatocarcinogenesis induced by hepatitis B virus (HBV) and aflatoxin B1 (AFB1) in tree shrews, and to reveal the role of these genes in hepatocarcinogenesis.METHODS: Tree shrews were divided into four groups:group A, those infected with HBV and fed with AFB1 (n = 39);group B, those infected with HBV alone (n = 28); group C,those fed with AFB1 alone (n = 29); and group D, normal controls (n = 20). The tree shrews underwent liver biopsies once every 15 wk. Expression of p53 and p21 proteins and genes in the biopsies and tumor tissues of the experimental tree shrews was detected, respectively, by immunohistochemistry,and by Southem blotting and reverse transcription-polymerase chain reaction and sequencing.RESULTS: The incidence of hepatocellular carcinomas (HCC) was higher in group A (66.7%) than that in group B (3.57%) and C (30%). The time of HCC occurrence was also earlier in group A than that in group C (120.0±16.6 wk vs 153.3±5.8 wk, respectively, P<0.01). p53 protein was not detected by immunohistochemistry in all groups before the 75^th wk of the experiment. At the 105^th wk, the positive rates fo p53 were 78.6%, 60% and 71.4% in groups A, B and C, respectively, which were significantly higher than that in group D (10%) (all P<0.05). An abnormal band of p53 gene was observed in groups A and C. The mutation points of p53gene in tree shrews with HCC were at codons 275, 78 and 13. The nucleotide sequence and amino acid sequence of tree shrew's wild-type p53 showed 91.7% and 93.4% homologies with those of human p53,respectively. The immunopositivity for p21 was found before HCC development. The incidence of HCC was significantly higher in tree shrews that were positive for p21 than those negative for p21 (80.0% vs 11.0%, P<0.001).The incidence of HCC in p21 positive animals in group A was significantly higher than those positive for p21 in group C (P<O.05).CONCLUSION: A remarkable synergistic effect on HCC development exists between HBV and AFB1. p53 mutation promotes the development of HCC. HBV and AFB1 may synergistically induce p53 gene mutation, and stimulate ras gene expression, ras gene is activated at the earlier stage during hepatocarcinogenesis, p21 protein may be an early marker, and the alterations of p53 may be a late event in the development of HCC.
基金Supported by The 21st century Frontier Program in the Functional Human Genome Project,No.HGM0200934the International Collaboration Program of Science and Technology,No. FGM0600914+1 种基金the Research Program for New Drug Target Discovery Grant from the Ministry of Education,Science & Technology,No.NBM3300711the KRIBB Research Initiative Program Grant,No.KGM3320911
文摘AIM:To investigate the role of hepatitis B virus X-protein(HBx)-induced reactive oxygen species(ROS)on liver carcinogenesis in HBx transgenic mice and HepG2-HBx cells.METHODS:Cell growth rate was analyzed,and through western blotting,mitogenic signaling was observed.Endogenous ROS from wild and HBx transgenic mice and HepG2-Mock and HBx cells were assayed by FACS-calibur.Identification of oxidized and reduced phosphatase and tensin homolog(PTEN)was analyzed through N-ethylmaleimide alkylation,nonreducing electrophoresis.RESULTS:We observed that the cell-proliferation-related phosphoinositide 3-kinase/Akt pathway is activated by HBx in vivo and in vitro.Increased ROS were detected by HBx.Tumor suppressor PTEN,via dephosphorylation of Akt,was oxidized and inactivated by increased ROS.Increased oxidized PTEN activated the mitogenic pathway through over-activated Akt.However,treatment with ROS scavenger N-acetyl cysteine can reverse PTEN to a reduced form.Endogenously produced ROS also stimulated HBx expression.CONCLUSION:HBx induced ROS promoted Akt pathways via oxidized inactive PTEN.HBx and ROS maintained a positive regulatory loop,which aggravated carcinogenesis.
基金This work was supported by the National Natural Science Foundation of China(No.30670172)by the Korea Foundation for International Cooperation of Science and Technology(K/C0S)through a grant provided by the Korean Ministry of Science and Technology.
文摘Previous studies have demonstrated the possible role of several aquaporins in seed germination. But systematic investigation of the role ofaquaporin family members in this process is lacking. Here, the developmental regulation of plasma membrane intrinsic protein （PIP） expression throughout germination and post-germination processes in rice embryos was analyzed. The expression patterns of the PIPs suggest these aquaporins play different roles in seed germination and seedling growth. Partial silencing of the water channel genes, OsPIP1;1 and OsPIP1：3, reduced seed germination while over-expression of OsPIP1：3 promoted seed germination under water-stress conditions. Moreover, spatial expression analysis indicates that OsPIP1：3 is expressed predominantly in embryo during seed germination. Our data also revealed that the nitric oxide （NO） donors, sodium nitroprusside （SNP） and S-nitrosoglutathione （GSNO）, promoted seed germination; furthermore, the NO scavenger, 2-（4-carboxyphenyl）-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide, inhibited germination and reduced the stimulative effects of SNP and GSNO on rice germination. Exogenous NO stimulated the transcription of OsPIP1：1, OsPIP1：2, OsPIP1：3 and OsPIP2：8 in germinating seeds. These results suggest that water channels play an important role in seed germination, acting, at least partly, in response to the NO signaling pathway.
基金Supported by Grants from the genomics program of the National Research Foundation of Korea funded by the Ministry of ScienceICT+4 种基金and Future PlanningNRF-2012M3A9D1054670 and NRF-2014M3C9A3068554(to Kim SY)Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of EducationNRF-2013R1A1A2006621(to Kim M)the Korea Research Institute of Bioscience and Biotechnology research initiative grant
文摘Gastric cancer is a complex disease that is affected by multiple genetic and environmental factors. For the precise diagnosis and effective treatment of gastric cancer, the heterogeneity of the disease must be simplified; one way to achieve this is by dividing the disease into subgroups. Toward this effort, recent advances in high-throughput sequencing technology have revealed four molecular subtypes of gastric cancer, which are classified as Epstein-Barr viruspositive, microsatellite instability, genomically stable, and chromosomal instability subtypes. We anticipate that this molecular subtyping will help to extend our knowledge for basic research purposes and will be valuable for clinical use. Here, we review the genomic and epigenomic heterogeneity of the four molecular subtypes of gastric cancer. We also describe a mutational meta-analysis and a reanalysis of DNA methylation that were performed using previously reported gastric cancer datasets.
基金The Long-Term Research Grant(LRGS)of the Ministry of Education of Malaysia supported this work
文摘Background:Increasing understanding on the functions of amino acids (AA) has led to new commercial applications and expansion of the worldwide markets.However,the current technologies rely heavily on non-food grade microorganism and chemical synthesis for the production of AA.Several studies reported that lactic acid bacteria (LAB) have the capability of producing AA owing to their well-established proteolytic system and amino acid biosynthesis genes.Hence,the objectives of this study were to explore the extracellular proteolytic activity of LAB isolated from various Malaysian fermented foods and their potential to produce AA extracellularly as feed supplements.Results:All the studied LAB isolates were versatile extracellular protease producers,whereby extracellular protease activities were detected from acidic to alkaline pH (pH 5,pH 6.5,pH 8) using qualitative and quantitative proteolytic assays.The highest proteolytic activity at pH 5 (15.76 U/mg) and pH 8 (19.42 U/mg) was achieved by Lactobacillus plantarum RG14,while Lactobacillus plantarum RS5 exhibited the highest proteolytic activity of 17.22 U/mg at pH 6.5.As for the results of AA production conducted in de Man,Rogosa and Sharpe medium and analysed by high pressure liquid chromatography system,all LAB isolates were capable of producing an array of AA.Generally,Pediococcus sp.showed greater ability for AA production as compared to Lactobacillus sp.Moreover,the studied LAB were able to produce a few major feed supplement AA such as methionine,lysine,threonine and tryptophan.P.pentosaceus TL-3 recorded the highest methionine and threonine productivity of 3.72 mg/L/h and 5.58 mg/L/h respectively.However,L.plantarum I-UL4 demonstrated a lysine productivity of 1.24 mg/L/h,while P.acidilactici TP-6 achieved up to 1.73 mg/L/h of tryptophan productivity.Conclusion:All the 17 studied LAB isolates possessed versatile extracellular proteolytic system and have vast capability of producing various amino acids including a few major feed supplement AA such as methionine,lysine,threonine and tryptophan.Despite AA production was strain dependent,the studied LAB isolates possessed vast potential and can be exploited further as a bio-agent or an alternative amino acids and bioactive peptide producers.
基金Korea Research Foundation,No.2016R1E1A1A02919844 to Kim JC and No.2017R1A2B1009062 to Roh SAMinistry of Science,ICT,and Future Planning,Republic of Koreathe Asan Institute for Life Sciences,No.2016-710 to Lee JL
文摘BACKGROUND Genomic profiling of tumors has contributed to the understanding of colorectal cancer(CRC), facilitating diagnosis, prognosis and selection of treatments,including targeted regimens. A report suggested that a 19-gene-based risk classifier(TCA19) was a prognostic tool for patients with stage III CRC. The survival outcomes in patients with stage IV CRC are still poor and appropriate selection of targeted therapies and immunotherapies is challenging.AIM To assess clinical implication of TCA19 in patients with stage IV CRC, and to identify TCA19 with involvement in immune-oncology.METHODS A retrospective review of the medical records of 60 patients with stage IV CRC was conducted, assessing clinicopathological variables and progression-free survival(PFS). TCA19 gene expression was determined by quantitative polymerase chain reaction(qPCR) in matched normal and tumor tissues taken from the study cohort. Expression of potential immune-oncology regulatory proteins and targets was examined by immunohistochemistry(IHC), western blot, immunofluorescence staining in tissues from a validation cohort of 10 patients, and in CRC cell lines co-cultured with monocyte in vitro.RESULTS In the patients with TCA19 score higher than the median, the PFS rates of eight patients who received the targeted regimens were significantly higher than the PFS rates of four patients who received 5-fluorouracil-based regimen(P = 0.041).In multivariate analysis, expression of signaling lymphocytic activation molecule family, member 7(SLAMF7) and triggering receptor expressed on myeloid cells 1(TREM1) was associated with PFS in the 60-patient cohort. After checking another 10 validate set, the expression of the IHC, the level of real-time qPCR,and the level of western blot were lower for SLAMF7 and higher for TREM7 in primary and metastatic tumors than in normal tissues. In CRC cells expressing SLAMF7 that were co-cultured with a monocytic cell line, levels of CD 68 and CD73 were significantly lower at day 5 of co-culture than at day 0.CONCLUSION The TCA19 score might be prognostic for target-regimen-specific PFS in stage IV CRC. Down-regulation of SLAMF7 and up-regulation of TREM1 occur in primary and metastatic tumor tissues.
文摘AIM: Irritable bowel syndrome (IBS) is a functional bowel disorder. Its major symptom is bowel dysmotility, yet the mechanism of the symptom is poorly understood. Since the neurokinin-1 receptor (NK1R)-mediated signaling in the gut is important in the control of normal bowel motor function,we aimed to investigate whether the NK1R-mediated bowel motor function was altered in IBS, using a rat IBS model that was previously reported to show colonic dysmotility in response to restraint stress.METHODS: IBS symptoms were produced in male SpragueDawley rats by inducing colitis with acetic acid. Rats were left to recover from colitis for 6 d, and used for experiments 7 d post-induction of colitis. Motor activities of distal colon were recorded in vitro.RESULTS: The contractile sensitivity of isolated colon to a NK1R agonist [Sar9, Met(O2)11]-substance P (1-30 nmol/L)was higher in IBS rats than that in normal rats. After the enteric neurotransmission was blocked by tetrodotoxin (TTX, 1 μmol/L), the contractile sensitivity to the NK1R agonist was increased in normal colon but not in IBS rat colon. The NK1R agonist-induced contraction was not different between the two groups when the agonist was challenged to the TTX-treated colon or the isolated colonic myocytes. A nitric oxide synthase inhibitor Nω-nitro-L-arginine methyl ester (L-NAME, 100 μmol/L) augmented the NK1R agonist-induced contraction only in normal rat colon.CONCLUSION: These results suggest that the NK1R-meidated colonic motor response is increased in IBS rats, due to the decrease in the nitrergic inhibitory neural component.
基金Supported by Research University Grant Scheme(RUGS)Project No.05-02-11-1404RU(Vote No.9300364)from Universiti Putra MalaysiaHigher Institutions Centre of Excellence(HICOE)Research Fund(Vote No.6369100)
文摘Objective: To compare the in vitro antioxidant capacity of a diatom, Chaetoceros calcitrans(C. calcitrans) extracted using six types of solvents.Methods: Each extract was evaluated in terms of extraction yield, total carotenoid,fucoxanthin content, total phenolic and antioxidant capacities(DPPH and ABTS +scavenging activity and iron chelating activity).Results: The methanol extract exhibited the highest yield [(22.71 ± 0.96) g/100 g dry weight(DW)], total carotenoid [(4.46 ± 0.36) mg/g DW], total phenolic [(2.49 ± 0.08) mg gallic acid equivalents/g DW] and second highest fucoxanthin content [(2.08 ± 0.03) mg fucoxanthin/g DW] as compared to other solvent extracts. Methanolic extract also exhibited significantly higher(P < 0.05) scavenging(DPPH, ABTS +) and iron chelating activities.Conclusions: Methanol was the recommended solvent for the production of antioxidant rich extract from C. calcitrans. Both carotenoids and phenolic acids were found to be positively correlated to the antioxidant capacities of C. calcitrans. Lead bioactives confirmed by subsequent high performance liquid chromatography studies were fucoxanthin, gallic acid and protocatechuic acid.
基金Fapemig(APQ-01833-11)for founding the field worka CNPq post-doc fellowship(153535/2018-0)CNPq(206814/2014-3)Post-doctorate scholarship
文摘Altitude and environmental variables such as edaphic properties are considered determinants of species distribution and community composition in mountain ecosystems.Here,we aimed to outline the effects of distinct mountain peaks,altitude and soil properties on community composition,species density,phylogenetic structure and diversity of angiosperm páramo communities from the Serra do Brigadeiro State Park,Minas Gerais,southeastern Brazil.For that,we identified all angiosperm species found in 300 plots(1 m×1 m)from three mountain peaks,measured soil depth and analyzed soil fertility and texture in each plot.To reduce the number of soil variables and species composition,we computed principal coordinates based on soil properties and principal coordinates based on species-plot matrix for each plot.Furthermore,we computed the standard effect sizes of the mean phylogenetic pairwise distance and the mean nearest phylogenetic taxon distance for each plot to investigate differences in the degree of relatedness among coexisting species.We compared differences in response variables between peaks and modelled them in function of altitude and principle components of soil properties using mixed effect models.Species density and phylogenetic diversity differed between peaks,but,contrary to the previous findings,no relationships between species richness or phylogenetic diversity and altitude or soil properties were found,indicating that further investigations are necessary to understand the altitude-biodiversity relationship in Brazilian páramo vegetation.Community composition differed between peaks and depended on altitude,soil properties and interactions between them,indicating that upward shifting of bioclimatic conditions due to climate changes may alter communities of this ecosystem.Phylogenetic structure differed between peaks and was influenced by altitude and soil properties.As phylogenetic clustering increased with altitude,eventual upward movements of species in Brazilian páramo vegetation due to climate change may alter community composition and the degree of relatedness among coexisting species,increasing the risk of species from higher altitudes to disappear.Therefore,conservation priorities arise for higher landscape portions,where these high altitude species may find refuges.
基金the Ministry of Agriculture of Malaysia for NKEA Research Grant Scheme fund (NRGS SP15-0600182)International Islamic University Malaysia for Publication Research Initiative Grant fund (PRIGS18-027-0027)
文摘The present study used in vitro and in silico techniques, as well as the metabolomics approach to characterise α-glucosidase inhibitors from different fractions of Clinacanthus nutans. C. nutans is a medicinal plant belonging to the Acanthaceae family, and is traditionally used to treat diabetes in Malaysia. nHexane, n-hexane: ethyl acetate(1:1, v/v), ethyl acetate, ethyl acetate: methanol(1:1, v/v), and methanol fractions were obtained via partitioning of the 80% methanolic crude extract. The in vitro α-glucosidase inhibitory activity was analyzed using all the fractions collected, followed by profiling of the metabolites using liquid chromatography combined with mass spectrometry. The partial least square(PLS) statistical model was developed using the SIMCA P^+14.0 software and the following four inhibitors were obtained:(1) 4,6,8-Megastigmatrien-3-one;(2) N-Isobutyl-2-nonen-6,8-diynamide;(3) 1′,2′-bis(acetyloxy)-3′,4′-didehydro-2′-hydro-β, ψ-carotene; and(4) 22-acetate-3-hydroxy-21-(6-methyl-2,4-octadienoate)-olean-12-en-28-oic acid. The in silico study performed via molecular docking with the crystal structure of yeast isomaltase(PDB code: 3 A4 A) involved a hydrogen bond and some hydrophobic interactions between the inhibitors and protein. The residues that interacted include ASN259, HID295, LYS156, ARG335,and GLY209 with a hydrogen bond, while TRP15, TYR158, VAL232, HIE280, ALA292, PRO312, LEU313,VAL313, PHE314, ARG315, TYR316, VAL319, and TRP343 with other forms of bonding.
基金supported by the Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(No.2018R1A6A1A03025582).
文摘This study represents a well-dispersed gold nanoparticles(AuNPs)synthesis process via cellulose nanocrystals(CNC)which acts as both reducing and supporting agent.The synthesis process was ultrafast and completed in a few seconds using microwave irradiation.The entire synthesis process was cost-effective,sustainable and eco-friendly.The synthesized(AuNPs/CNC)nanocomposite was investigated by transmission electron microscopy,selected area electron diffraction,Fourier transform infrared spectroscopy,energy dispersive X-ray analysis,X-ray diffraction,and UV–vis spectroscopy.The obtained AuNPs were well accumulated on the CNC surface and had a uniform spherical shape with an average diameter of 8±5.3 nm.The diameter of AuNPs could be altered by tuning the concentration of CNC suspension.The synthesized AuNPs/CNC nanocomposite film exhibited excellent degradation properties against various organic dyes,namely,Allura red,Congo red,Rhodamine B and Amaranth.The ultrafast degradation reactions followed pseudo first order kinetics.In the catalytic degradation reaction,AuNPs/CNC was transmitting electrons from a donor(NaBH4)to an acceptor(a dye).
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Science,ICT and Future Planning(NRF-2013R1A2A2A01068190)Hallym University Specialization Fund(HRF-S-13)
文摘In this study,we tried to verify the neuroprotective effect of Chrysanthemum indicum Linne(CIL)extract,which has been used as a botanical drug in East Asia,against ischemic damage and to explore the underlying mechanism involving the anti-inflammatory approach.A gerbil was given CIL extract for 7 consecutive days followed by bilateral carotid artery occlusion to make a cerebral ischemia/reperfusion model.Then,we found that CIL extracts protected pyramidal neurons in the hippocampal CA1 region(CA1)from ischemic damage using neuronal nucleus immunohistochemistry and Fluoro-Jade B histofluorescence.Accordingly,interleukin-13 immunoreactivities in the CA1 pyramidal neurons of CIL-pretreated animals were maintained or increased after cerebral ischemia/reperfusion.These findings indicate that the pre-treatment of CIL can attenuate neuronal damage/death in the brain after cerebral ischemia/reperfusion via an anti-inflammatory approach.
基金supported by Grants from the R&D Convergence Program of National Research Council of Science & Technology (No. CAP-16-02-KIST)the National Research Foundation of Korea (No. NRF-2016M3A9B6918584)
文摘Chikungunya fever is a vector-borne viral disease transmitted to humans by chikungunya virus(CHIKV)-infected mosquitoes.There have been many outbreaks of CHIKV infection worldwide,and the virus poses ongoing risks to global health.To prevent and control CHIKV infection,it is important to improve the current CHIKV diagnostic approaches to allow for the detection of low CHIKV concentrations and to correctly distinguish CHIKV infections from those due to other mosquito-transmitted viruses,including dengue virus(DENV),Japanese encephalitis virus(JEV),and Zika virus(ZIKV).Here,we produced monoclonal antibodies(mAbs)against the CHIKV envelope 2 protein(CHIKV-E2)and compared their sensitivity and specificity with commercially available mAbs using enzyme-linked immunosorbent assays(ELISA).Two anti-CHIKV-E2 mAbs,19-1 and 21-1,showed higher binding affinities to CHIKV-E2 protein than the commercial mAbs did.In particular,the 19-1 mAb had the strongest binding affinity to inactivated CHIKV.Moreover,the 19-1 mAb had very little cross-reactivity with other mosquito-borne viruses,such as ZIKV,JEV,and DENV.These results suggest that the newly produced anti-CHIKV-E2 mAb,19-1,could he used for CHIKV diagnostic approaches.
基金supported by the research fund of Chungnam National University,Republic of Koreasupported by the Li Kashing Foundation at Shantou University Medical College,China
文摘Clusterin, a protein associated with multiple functions, is expressed in a wide variety of mammalian tissues. Although clusterin is known to be involved in neurodegenerative diseases, ageing, and tumorigenesis, a detailed analysis of the consequences of gain- or loss-of- function approaches has yet to be performed to understand the underlying mechanisms of clusterin functions. Since clusterin levels change in neurological diseases, it is likely that clusterin contributes to cell death and degeneration in general. Zebrafish was investigated as a model system to study human diseases. During development, zebrafish clusterin was expressed in the notochord and nervous system. Embryonic overexpression of clusterin by mRNA microinjection did not affect axis formation, whereas its knock-down by anti-sense morpholino treatment resulted in neuronal cell death. To analyze the function of clusterin in neurodegeneration, a transgenic zebrafish was investigated, in which nitroreductase expression is regulated under the control of a neuron-specifc huC promoter which is active between the stages of early neuronal precursors and mature neurons. Nitroreductase turns metronidazole into a cytotoxic agent that induces cell death within 12 h. After metronidazole treatment, transgenic zebrafish showed neuron-specific cell death. Interestingly, we also observed a dramatic induction of clusterin expression in the brain and spinal cord in these fish, suggesting a direct or indirect role of clusterin in neuronal cell death and thus, more generally, in neurodegeneration.
基金supported by a grant from the KRIBB Research Initiative Program(KGM2211531)supported by Priority Research Centers Program through NRF funded by the Ministry of Education,Science and Technology (2015R1A6A1A04020885)
文摘Dietary polyunsaturated fatty acids （PUFAs）, which are abundant in marine fish oils, have recently received global attention for their prominent anti-obesogenic effects. Among PUFAs, eicosapentaenoic acid （EPA; 20：5n-3） and docosahexaenoic acid （DHA; 22：6n-3）, which are n-3 long-chain PUFAs widely referred to as omega-3 oils, were reported to prevent the development of obesity in rodents and humans. In the present study, we evaluated the anti-obesity effects of microalgal oil on high-fat induced obese C57BL/6 mice, compared with commercial omega-3 fish oil and vegetable corn oil. Microalgal oil is an inherent mixture of several PUFAs, including EPA, DHA and other fatty acids produced from a marine microalgal strain of Thraustochytriidae sp. derived mutant. It was found to contain more PUFAs （〉80%） and more omega-3 oils than commercial omega-3 fish oil （PUFAs 〉31%） and corn oil （PUFAs 59%）. All three types of oils induced weight loss in high-fat-induced obese mice, with the loss induced by microalgal oil being most significant at 9 weeks （10% reduction）. However, the oils tested did not improve blood lipid levels, although microalgal oil showed an apparent inhibitory effect on lipid accumulation in the liver. These findings may be attributed to the higher PUFA content, including omega-3 oils of microalgal oil than other oils. Collectively, these findings suggest that microalgal oil, derived from Thraustochytriidae sp. derived mutant, is a prominent candidate for replacement of omega-3 fish oils based on its apparent anti-obesity effect in vivo.
