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1.
The fractional uptake of ingested aluminium and aluminium compounds (aluminium citrate, aluminium nitrate, aluminium chloride, aluminium sulphate, aluminium hydroxide, aluminium oxide, aluminium metal, powdered aluminium pot electrolyte, acidic sodium aluminium phosphate (SALP), basic sodium aluminium phosphate (Kasal), sodium aluminium silicate and FD&C red 40 aluminium lake) from the gastro-intestinal tract of adult female rats was measured. This was determined by comparing retained body burden of 26Al at seven days post-admistration of an i.v. injection of 26Al-labelled aluminium citrate with that retained following the gastric admistration of 26Al-labelled test compounds as either solutions or suspended solid. The calculated percentage uptake of 26Al for all the aluminium solutions was similar: aluminium citrate 0.08%, aluminium chloride 0.05%, aluminium nitrate 0.05% and aluminium sulphate 0.21%. The uptake of 26Al administered as insoluble particulates was lower: 0.03% for aluminium hydroxide; 0.02% for aluminium oxide; 0.04% for powdered pot electrolyte; 0.12% for sodium aluminium silicate; and 0.09% for FD&C red 40 aluminium lake. For aluminium metal, SALP and Kasal the amount of 26Al present in the rats was insufficient to determine uptake and was less than 0.03%. The results produced for aluminium citrate, aluminium hydroxide and aluminium sulphate are close to those published for man.  相似文献   
2.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged as a new human pathogen in late 2019 and it has infected over 100 million people in less than a year. There is a clear need for effective antiviral drugs to complement current preventive measures, including vaccines. In this study, we demonstrate that berberine and obatoclax, two broad-spectrum antiviral compounds, are effective against multiple isolates of SARS-CoV-2. Berberine, a plant-derived alkaloid, inhibited SARS-CoV-2 at low micromolar concentrations and obatoclax, which was originally developed as an anti-apoptotic protein antagonist, was effective at sub-micromolar concentrations. Time-of-addition studies indicated that berberine acts on the late stage of the viral life cycle. In agreement, berberine mildly affected viral RNA synthesis, but it strongly reduced infectious viral titers, leading to an increase in the particle-to-pfu ratio. In contrast, obatoclax acted at the early stage of the infection, which is in line with its activity to neutralize the acidic environment in endosomes. We assessed infection of primary human nasal epithelial cells that were cultured on an air-liquid interface and found that SARS-CoV-2 infection induced and repressed expression of specific sets of cytokines and chemokines. Moreover, both obatoclax and berberine inhibited SARS-CoV-2 replication in these primary target cells. We propose berberine and obatoclax as potential antiviral drugs against SARS-CoV-2 that could be considered for further efficacy testing.  相似文献   
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《Drug discovery today》2022,27(6):1733-1742
Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.  相似文献   
5.
ObjectiveTo investigate the potential anti-tumor mechanisms of naphthoquinone compound shikonin (SKN) extracted from the root of Chinese herbal medicine plant lithospermum (Lithospermum erythrorhizon Sieb. & Zucc.).MethodsWe first observed that SKN treatment led to swelling and bubbles in HeLa cells that were similar to the phenotype of cell pyroptosis. Subsequently, the HeLa cells experienced a pyroptotic process with SKN, and this was then assessed using lactate dehydrogenase (LDH) release and propidium iodide (PI)/Hoechst double staining experiments. Pyroptosis is defined as gasdermin-mediated programmed necroptosis. To identify the potential pyroptosis machinery, two strategies were utilized that included a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein 9 screening experiment and a pyroptosis reconstitution assay executed by each of the five known gasdermins (GSDMA-E). Moreover, endogenous cleavage was also detected in a panel of tumor cell lines.ResultsCompared with the control, both the LDH release and PI/Hoechst double-staining experiments suggested that SKN induced perforation and enhancement of the permeability of the cell membranes that resulted in pyroptosis in HeLa cells (P = .028 and P = .032, respectively). In addition, the reconstitution assays in human embryonic kidney 293T (HEK-293T) cells and endogenous cleavage assays in HeLa cells indicated that the pyroptosis was controlled by GSDME. In addition, we also found SKN could trigger pyroptosis in a panel of tumor cell lines in which the cellular morphologies were proportional to the GSDME expression levels. Additionally, the cleavage of GSDME was also detected, and this was indicative of a similar GSDME-mediated mechanism.ConclusionOur study not only explained the molecular mechanism of cytotoxicity of SKN to various tumor cells, but also provided additional information for the potential clinical application of natural naphthoquinone compounds against cancer.  相似文献   
6.
Species identification of unknown biological samples is crucial for forensic applications, especially in cases of explosion, disaster accidents, and body mutilation after murdering, as well as poaching, illegal trade in endangered animals, and meat food fraud. In this study, we identified 60 volatile organic compounds (VOCs) in fresh skeletal muscle tissues of seven different animal species (cattle, sheep, pigs, rabbits, rats, chickens and carp) and a human dead body by headspace-gas-chromatography ion-mobility spectrometry (HS-GC-IMS), and compared their differences by retention time, drift time and molecular weight. The results showed that these VOCs formed different gallery plot fingerprints in the skeletal muscle tissues of the human dead body and seven animal species. Principal component analysis (PCA) showed significantly different fingerprints between these species, and these fingerprints maintained good stability between the species and within the same species. Some VOCs have high species specificity, while VOCs of human fresh muscle tissues from different individual sources have little difference, demonstrating that all tested muscle tissue samples could be distinguished based on different VOCs. HS-GC-IMS has proved to be a rapid, high-throughput, highly sensitive and specific species identification method, which can be used for forensic species identification in criminal cases and disaster accidents, as well as detection in the field of food safety, such as meat fraud and adulteration.  相似文献   
7.
目的:从HPLC指纹图谱、指标性成分含量、出膏率、密度及pH值方面,多维度评价传统瓦锅煎煮与现代机器煎煮所得小柴胡汤的质量。方法:分别采用传统瓦锅煎煮法、机器常压一煎法和机器常压两煎法制备汤液。HPLC色谱柱为Agilent ZORBAX SB-C18(250 mm×4.6 mm,5 μm),检测波长为205 nm,流动相为乙腈-0.1%磷酸水溶液,柱温为30 ℃,流速为1.0 mL·min-1,检测的指标性成分有甘草苷、甘草酸铵、黄芩苷、人参皂苷Rg1、人参皂苷Rb1、柴胡皂苷a和柴胡皂苷d。结果:3种方法制备的小柴胡汤HPLC指纹图谱相似度大于99%;机器两煎法中甘草苷、柴胡皂苷d的含量高于瓦锅煎煮(P<0.05),其余成分的含量、出膏率、密度与瓦锅煎煮无统计学差异(P>0.05);机器一煎法中人参皂苷Rg1、人参皂苷Rb1、柴胡皂苷a的含量低于瓦锅煎煮(P<0.05),其余成分的含量与瓦锅煎煮无统计学差异,机器一煎的出膏率和密度虽低于瓦锅煎煮,但均达到了瓦锅煎煮的90%以上。结论:小柴胡汤现代机器煎煮与传统瓦锅煎煮的质量无明显差异。  相似文献   
8.
Introduction: Boron-containing compounds induce effects on immune responses. Such effects are interesting to the biomedical field for the development of therapeutic tools to modulate the immune system.

Areas covered: The scope of BCC use to modify immune responses is expanding, mainly with regard to inflammatory diseases. The information was organized to demonstrate the breadth of reported effects. BCCs act as modulators of innate and adaptive immunity, with the former including regulation of cluster differentiation and cytokine production. In addition, BCCs exert effects on inflammation induced by infectious and noninfectious agents, and there are also reports regarding their effects on mechanisms involving hypersensitivity and transplants. Finally, the authors discuss the beneficial effects of BCCs on pathologies involving various targets and mechanisms.

Expert opinion: Some BCCs are currently used as drugs in humans. The mechanisms by which these BCCs modulate immune responses, as well as the required structure–activity relationship for each observed mechanism of action, should be clarified. The former will allow for the development of improved immunomodulatory drugs with extensive applications in medicine. Patenting trends involve claims concerning the synthesis and actions of identified molecules with a defined profile regarding cytokines, cell differentiation, proliferation, and antibody production.  相似文献   

9.
Background and aimThis network meta-analysis (NMA) compares the effects of different types of olive oil (OO) on cardiovascular risk factors.Methods and resultsLiterature search was conducted on three electronic databases (Medline, Web of Science, and Cochrane Central). Inclusion criteria: Randomized controlled trials (RCTs) (≥3 weeks duration of intervention) comparing at least two of the following types of OO: refined OO (ROO), mixed OO (MOO), low phenolic (extra) virgin OO (LP(E)VOO), and high phenolic (extra) virgin OO (HP(E)VOO). Random-effects NMA was performed for seven outcomes; and surface under the cumulative ranking curve (SUCRA) was estimated, using an analytical approach (P-score). Thirteen RCTs (16 reports) with 611 mainly healthy participants (mean age: 26–70 years) were identified. No differences for total cholesterol, HDL-cholesterol, triacylglycerols, and diastolic blood pressure were observed comparing ROO, MOO, LP(E)VOO and HP(E)VOO. HP(E)VOO slightly reduce LDL-cholesterol (LDL-C) compared to LP(E)VOO (mean difference [MD]: −0.14 mmol/L, 95%–CI: −0.28, −0.01). Both, HP(E)VOO and LP(E)VOO reduces SBP compared to ROO (range of MD: −2.99 to −2.87 mmHg), and HP(E)VOO may improve oxidized LDL-cholesterol (oxLDL-C) compared to ROO (standardized MD: −0.68, 95%–CI: −1.31, −0.04). In secondary analyses, EVOO may reduce oxLDL-C compared to ROO, and a dose-response relationship between higher intakes of phenolic compounds from OO and lower SBP and oxLDL-C values was detected. HP(E)VOO was ranked as best treatment for LDL-C (P-score: 0.83), oxLDL-C (0.88), and SBP (0.75).ConclusionsHP(E)VOO may improve some cardiovascular risk factors, however, public health implications are limited by overall low or moderate certainty of evidence.  相似文献   
10.
Biguanides, including metformin and phenformin, have emerged as promising anticancer agents. However, the high dose needed for their efficient anticancer properties restricts their clinical application. In an attempt to obtain higher active compounds than these parent compounds, pyrazole‐containing biguanide derivatives were synthesized and screened for in vitro cytotoxicity against human cancer cell lines. Clonogenic assays and scratch wound healing assays demonstrated that these new derivatives profoundly inhibit cell proliferation and migration. Compounds 10b and 10d exhibited strong potency with low IC50 values in the range of 6.9‐28.3 μM, far superior to phenformin and metformin. Moreover, 20 μM 10b and 10d resulted in 72.3‐88.2% (p < 0.001) inhibition of colony formation and 29.3‐60.7% (p < 0.05) inhibition of cell migration. Mechanistically, 10b and 10d activated adenosine monophosphate‐activated protein kinase, leading to inactivation of the mammalian target of rapamycin (mTOR) signaling pathway with the regulation of 4EBP1 and p70S6K. These results suggest the value of these novel biguanide derivatives as candidates with therapeutic potential for the treatment of bladder and ovarian cancer.  相似文献   
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