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1.
Dr. Anders Højgaard Hansen Henriette B. Christensen Dr. Sunil K. Pandey Dr. Eugenia Sergeev Alice Valentini Julia Dunlop Domonkos Dedeo Simone Fratta Dr. Brian D. Hudson Prof. Graeme Milligan Prof. Trond Ulven Prof. Elisabeth Rexen Ulven 《ChemMedChem》2021,16(21):3326-3341
Free fatty acid receptor 2 (FFA2) is a sensor for short-chain fatty acids that has been identified as an interesting potential drug target for treatment of metabolic and inflammatory diseases. Although several ligand series are known for the receptor, there is still a need for improved compounds. One of the most potent and frequently used antagonists is the amide-substituted phenylbutanoic acid known as CATPB ( 1 ). We here report the structure-activity relationship exploration of this compound, leading to the identification of homologues with increased potency. The preferred compound 37 (TUG-1958) was found, besides improved potency, to have high solubility and favorable pharmacokinetic properties. 相似文献
2.
JAVARIA AFZAL XIUKANG WANG MUHAMMAD HAMZAH SALEEM XUECHENG SUN SHAHID HUSSAIN IMRAN KHAN MUHAMMAD SHOAIB RANA SHAKEEL AHMED SAMRAH AFZAL AWAN SAJID FIAZ OMAR AZIZ KASHIF ALI KUBAR SHAFAQAT ALI CHENGXIAO HU 《Biocell》2021,45(6):1631-1649
Soil contamination with toxic heavy metals [such as cadmium (Cd)] is becoming a serious global problem due
to rapid development of social economy. Iron (Fe), being an important element, has been found effective in enhancing
plant tolerance against biotic and abiotic stresses. The present study investigated the extent to which different levels of
Ferrous sulphate (FeSO4) modulated the Cd tolerance of rice (Oryza sativa L.), when maintained in artificially Cd
spiked regimes. A pot experiment was conducted under controlled conditions for 146 days, by using natural soil,
mixed with different levels of CdCl2 [0 (no Cd), 0.5 and 1 mg/kg] together with the exogenous application of FeSO4
at [0 (no Fe), 1.5 and 3 mg/kg] levels to monitor different growth, gaseous exchange characteristics, oxidative stress,
antioxidative responses, minerals accumulation, organic acid exudation patterns of O. sativa. Our results depicted that
addition of Cd to the soil significantly (P < 0.05) decreased plant growth and biomass, gaseous exchange parameters,
mineral uptake by the plants, sugars (soluble, reducing, and non-reducing sugar) and altered the ultrastructure of
chloroplasts, plastoglobuli, mitochondria, and many other cellular organelles in Cd-stressed O. sativa compared to
those plants which were grown without the addition of Cd in the soil. However, Cd toxicity boosted the production of
reactive oxygen species (ROS) by increasing the contents of malondialdehyde (MDA), which is the indication of
oxidative stress in O. sativa and was also manifested by hydrogen peroxide (H2O2) contents and electrolyte leakage to
the membrane bounded organelles. Although, activities of various antioxidative enzymes like superoxidase dismutase
(SOD), peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX) and non-enzymatic antioxidants like
phenolics, flavonoid, ascorbic acid, anthocyanin and proline contents increased up to a Cd level of 0.5 mg/kg in the
soil but were significantly diminished at the highest Cd level of 1 mg/kg in the soil compared to those plants which
were grown without the addition of Cd in the soil. The negative impacts of Cd injury were reduced by the application
of FeSO4 which increased plant growth and biomass, improved photosynthetic apparatus, antioxidant enzymes, minerals uptake together with diminished exudation of organic acids as well as oxidative stress indicators in roots and
shoots of O. sativa by decreasing Cd retention in different plant parts. These results shed light on the effectiveness of
FeSO4 in improving the growth and upregulation of antioxidant enzyme activities of O. sativa in response to Cd
stress. However, further studies at field levels are required to explore the mechanisms of FeSO4-mediated reduction of
the toxicity of not only Cd, but possibly also other heavy metals in plants. 相似文献
3.
4.
Yajing Qi Yuying Yang Alkassoumi Hassane Hamadou Qiuyun Shen Bin Xu 《International Journal of Food Science & Technology》2022,57(4):2104-2112
Wheat bran is rich in functional ingredients, but the high level of lipase limits its applications. Tempering–preservation treatment (at 70–90 °C with moisture of 20%–40% for 1–4 h) was exploited for stabilising wheat bran and its effect on polyphenols was investigated. The results showed that more lipase was inactivated at higher tempering moisture, temperature and longer time. The optimum condition for inactivation of wheat bran lipase was 30% moisture and 90 °C for 4 h. The inactivation rate reached 93.8% with a residual enzyme activity of 0.264 U g−1. Under the optimum condition, the sum of free phenolic acids rose from 25.4 to 55.8 µg g−1. As for bound phenolic acids, there was a slight increase of hydroxybenzoic acid derivatives but a slight decrease of hydroxycinnamic acid derivatives. The total contents of phenolic acids before and after stabilisation were not significantly different. This study showed the possibility of using tempering–preservation as an efficient method for inactivation of wheat bran lipase while maintaining its phenolic compounds, which could be used in the production of whole wheat flour. 相似文献
5.
Ziqian He Na Deng Bisheng Zheng Tong Li Rui Hai Liu Ling Yuan Wenzhi Li 《International Journal of Food Science & Technology》2022,57(7):4268-4276
The changes in polyphenol fractions after in vitro fermentation of apple peel polyphenol (APP) by gut microbiota as well as the effects of APP on the growth, pH value, short-chain fatty acids (SCFAs) production and intestinal flora composition of gut microbiota fermentation were firstly explored in this study. The relative abundance of Lactobacillus in the APP group was 49.55% with an increment of 49.40% compared with the blank group, while that of Bifidobacterium was 13.32%. Moreover, the flora produced 37.093 ± 0.478 mM of SCFAs including acetic acid, propionic acid, butyric acid and valeric acid during the process of fermentation, thus reduced the environmental pH value. In addition, polyphenol fractions in APP were altered by gut microbiota fermentation to some extent, for example, glycosides were hydrolysed to aglycones. These findings suggested APP as a potential prebiotic agent to alleviate the disorder of intestinal flora. 相似文献
6.
《Journal of Great Lakes research》2022,48(5):1258-1269
Herring gulls (Larus argentatus) are used as ecological indicators of the coastal Lake Superior ecosystem in Pukaskwa National Park, Ontario, Canada. Their populations have declined by 70 % over the last 40 years, suggesting changes in the park ecosystem. Previous studies highlighted declining prey abundance as a possible contributing factor to population declines. Here, we assess herring gull diets via stable isotope (nitrogen, carbon) and fatty acid indicators to investigate how diet may influence population trends through effects on physiology (stress-related hormones), reproduction (egg size) and behavior (nest attentiveness). Diets were variable among individual herring gulls. Gulls utilizing anthropogenic food sources exhibited reduced levels of stress-associated hormones, increased egg size, and increased nest attentiveness. Anthropogenic food sources are likely buffering the impacts of declines in aquatic food availability; however, populations are still declining. Understanding factors contributing to population trends in ecological indicator species is critical for species management and for identifying stressors that are likely affecting the broader ecosystem. Herring gulls are archetypal examples of the “canary in a coalmine” indicator but in an ecosystem context. Changes in their diets and in variables associated with their physiology, reproduction, and behavior point to very significant changes occurring in the Lake Superior ecosystem. Integrated research across the Great Lakes is required to understand the extent of this change and its implications for the sustainability of wildlife populations. 相似文献
7.
Levi B. Richards Meng Li Gert Folkerts Paul A.J. Henricks Johan Garssen Betty C.A.M. van Esch 《International journal of molecular sciences》2021,22(1)
Barrier dysfunction of airway epithelium contributes to the development of allergies, airway hyper-responsiveness and immunological respiratory diseases. Short-chain fatty acids (SCFA) enhance and restore the barrier function of the intestinal epithelium. This study investigated whether acetate, propionate and butyrate enhance the integrity of bronchial epithelial cells. Differentiating human bronchial epithelial cells (16HBE) grown on transwells were exposed to butyrate, propionate and acetate while trans-epithelial electrical resistance was monitored over time. Restorative effects of SCFA were investigated by subsequent incubation of cells with IL-4, IL-13 or house dust mite extract and SCFA. SCFA effects on IL-4-induced cytokine production and the expression of zonula occludens-1 (ZO-1) and Mitogen-activated protein kinases (MAPK) signalling pathways were investigated by ELISA and Western blot assays. Propionate and butyrate enhanced the barrier function of differentiating 16HBE cells and induced complete recovery of the barrier function after exposure to the above-mentioned stimuli. Butyrate decreased IL-4-induced IL-6 production. IL-4 decreased ZO-1 protein expression and induced phosphorylation of extracellular signal-regulated protein kinases 1/2 (ERK1/2) and c-Jun N-terminal kinases (JNK) in 16HBE cells, both of which could be restored by SCFA. SCFA showed prophylactic and restorative effects on airway epithelial barrier function, which might be induced by increased ZO-1 expression. 相似文献
8.
Filip Hromcik Jan Vokurka Michal Kyr Lydie Izakovicova Holla 《European Journal of Lipid Science and Technology》2021,123(2):2000259
The topical application of aspirin and omega-3 polyunsaturated fatty acids (PUFAs) may trigger the resolution of inflammation by inducing the biosynthesis of pro-resolvers such as lipoxins and resolvins while also avoiding the side effects of systemic aspirin intake. This study assessed the effect of enhanced granulation tissue (EGT) on periodontal tissue regeneration through the local application of aspirin and omega-3 PUFAs directly to granulation tissue (GT) during periodontal surgery. This randomized controlled experiment assesses 38 pockets in 19 patients. In every patient, two similar intrabony periodontal defects are treated with an open flap debridement, one with EGT (GT extracted, enhanced with aspirin and omega-3 PUFAs, and replaced) and the other with standard GT removal. Clinical attachment level (CAL) and probing pocket depth (PPD) are assessed at baseline and 2 and 6 months after surgery. The experimental protocol (EGT) results in a greater CAL gain as compared to that in the controls at 6 months (p < 0.05), while PPD reduction is not affected. The retained GT does not compromise healing. EGT is proposed as a promising, inexpensive, and simple method that may improve the outcome of periodontal regenerative treatment. However, the described protocol requires optimization and further assessment. Practical Applications : The biosynthesis of mediators including resolvins and lipoxins triggered by aspirin and omega-3 PUFAs promote the resolution of inflammation, eventually leading to faster regeneration of inflamed tissues. While granulation tissue is a necessary component in wound healing, enhancing granulation tissue with aspirin and omega-3 PUFAs results in CAL gain in the surgical treatment of periodontal defects. Retained granulation tissue does not compromise periodontal healing. The EGT strategy is an inexpensive and simple method that may improve the clinical outcomes of regenerative periodontal procedures. 相似文献
9.
Dr. Jisook Lee Dr. Nyssa Drinkwater Prof. Sheena McGowan Prof. Peter Scammells 《ChemMedChem》2021,16(1):234-249
Aminopeptidase N (APN/CD13) is a zinc-dependent ubiquitous transmembrane ectoenzyme that is widely present in different types of cells. APN is one of the most extensively studied metalloaminopeptidases as an anti-cancer target due to its significant role in the regulation of metastasis and angiogenesis. Previously, we identified a potent and selective APN inhibitor, N-(2-(Hydroxyamino)-2-oxo-1-(3′,4′,5′-trifluoro-[1,1′-biphenyl]-4-yl)ethyl)-4-(methylsulfonamido)benzamide ( 3 ). Herein, we report the further modifications performed to explore SAR around the S1 subsite of APN and to improve the physicochemical properties. A series of hydroxamic acid analogues were synthesised, and the pharmacological activities were evaluated in vitro. N-(1-(3′-Fluoro-[1,1′-biphenyl]-4-yl)-2-(hydroxyamino)-2-oxoethyl)-4-(methylsulfonamido)benzamide ( 6 f ) was found to display an extremely potent inhibitory activity in the sub-nanomolar range. 相似文献
10.
Peng Li Haibin Jiang Ariel Barr Zhichu Ren Rui Gao Hua Wang Weiwei Fan Meifang Zhu Guiyin Xu Ju Li 《Advanced functional materials》2021,31(51):2105845
Mercury, lead, and cadmium are among the most toxic and carcinogenic heavy metal ions (HMIs), posing serious threats to the sustainability of aquatic ecosystems and public health. There is an urgent need to remove these ions from water by a cheap but green process. Traditional methods have insufficient removal efficiency and reusability. Structurally robust, large surface-area adsorbents functionalized with high-selectivity affinity to HMIs are attractive filter materials. Here, an adsorbent prepared by vulcanization of polyacrylonitrile (PAN), a nitrogen-rich polymer, is reported, giving rise to PAN-S nanoparticles with cyclic π-conjugated backbone and electronic conductivity. PAN-S can be coated on ultra-robust melamine (ML) foam by simple dipping and drying. In agreement with hard/soft acid/base theory, N- and S-containing soft Lewis bases have strong binding to Hg2+, Pb2+, Cu2+, and Cd2+, with extraordinary capture efficiency and performance stability. Furthermore, the used filters, when collected and electrochemically biased in a recycling bath, can release the HMIs into the bath and electrodeposit on the counter-electrode as metallic Hg0, Pb0, Cu0, and Cd0, and the PAN-S@ML filter can then be reused at least 6 times as new. The electronically conductive PAN-S@ML filter can be fabricated cheaply and holds promise for scale-up applications. 相似文献