Six new polyoxygenated terpenoids, podovirosanes A-F (
-
), and two known polyketides (
and
) were isolated from the roots of
. Their structures, along with absolute configurations, were deduced ...using spectroscopic analysis as well as computational calculations, including TDDFT calculation of ECD spectra and GIAO NMR calculations combined with DP4+ probability analysis. Compounds
,
,
, and
were found to reduce the phosphorylation levels of NF-
B p65 in SARS-CoV-2 pseudovirus-stimulated PMA-differentiated THP-1 cells.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Drug-metabolizing enzymes, particularly the cytochrome P450 (CYP450) monooxygenases, play a pivotal role in pharmacokinetics. CYP450 enzymes can be affected by various xenobiotic substrates, which ...will eventually be responsible for most metabolism-based herb-herb or herb-drug interactions, usually involving competition with another drug for the same enzyme binding site. Compounds from herbal or natural products are involved in many scenarios in the context of such interactions. These interactions are decisive both in drug discovery regarding the synergistic effects, and drug application regarding unwanted side effects. Herein, this review was conducted as a comprehensive compilation of the effects of herbal ingredients on CYP450 enzymes. Nearly 500 publications reporting botanicals' effects on CYP450s were collected and analyzed. The countries focusing on this topic were summarized, the identified herbal ingredients affecting enzyme activity of CYP450s, as well as methods identifying the inhibitory/inducing effects were reviewed. Inhibitory effects of botanicals on CYP450 enzymes may contribute to synergistic effects, such as herbal formulae/prescriptions, or lead to therapeutic failure, or even increase concentrations of conventional medicines causing serious adverse events. Conducting this review may help in metabolism-based drug combination discovery, and in the evaluation of the safety profile of natural products used therapeutically.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Drug resistance is an obstacle to the treatment of ovarian cancer. Using a unique cell model, we have proven previously that a subpopulation of ovarian cancer cells is more resistant to cisplatin ...than are the original cells. MicroRNAs (miRNAs), small noncoding RNAs, are involved in many biological events in cancer cells. In our study, we explored whether miRNAs are involved in cisplatin resistance of ovarian cancer cells. Cisplatin‐resistant cells expressed a lower level of miR‐29a/b/c. Manipulation of microRNA‐29 (miR‐29) expression modulated cisplatin sensitivity of CP70, HeyC2, SKOV3 and A2780 ovarian cancer cells. Knockdown of miR‐29a/b/c increased the ability of cells to escape cisplatin‐induced cell death partly through upregulation of collagen type I alpha 1 (COL1A1) and increased the activation of extracellular signal‐regulated kinase 1/2 and inactivation of glycogen synthase kinase 3 beta. When combined with cisplatin treatment, knockdown of miR‐29 decreased the amount of the active form of caspase‐9 and caspase‐3. Ectopic expression of miR‐29 alone or in combination with cisplatin treatment efficaciously reduced the tumorigenicity of CP70 cells in vivo. Our data show that downregulation of miR‐29 increases cisplatin resistance in ovarian cancer cells. Taken together, these data suggest that overexpression of miR‐29 is a potential sensitizer to cisplatin treatment that may have therapeutic implications.
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MicroRNAs (miRNAs) are small, noncoding RNAs that are involved in a number of processes in cancer cells. In this study, the authors found that overexpression of miR‐29 can reduce drug resistance in ovarian cancer cells, in part through increased expression of collagen. Ectopic expression of miR‐29 alone or in combination with cisplatin treatment also reduced the tumorigenicity of CP70 cells in vivo. These data suggest that overexpression of miR‐29 may sensitize tumor cells to cisplatin treatment, and that this miRNA may therefore have therapeutic potential.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Ferroptosis is a form of regulated cell death that is characterized by the accumulation of iron-dependent lipid peroxides. The regulation of ferroptosis involves both non-enzymatic reactions and ...enzymatic mechanisms. Natural products have demonstrated potential effects on various enzymes, including GPX4, HO-1, NQO1, NOX4, GCLC, and GCLM, which are mainly involved in glutathione metabolic pathway or oxidative stress regulation, and ACSL3 and ACSL4, which mainly participate in lipid metabolism, thereby influencing the regulation of ferroptosis. In this review, we have provided a comprehensive overview of the existing literature pertaining to the effects of natural products on enzymes involved in ferroptosis and discussed their potential implications for the prevention and treatment of ferroptosis-related diseases. We also highlight the potential challenge that the majority of research has concentrated on investigating the impact of natural products on the expression of enzymes involving ferroptosis while limited attention is given to the regulation of enzyme activity. This observation underscores the considerable potential and scope for exploring the influence of natural products on enzyme activity.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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•Hydrophobic DESs are easily prepared, less viscous, thermostable, and inexpensive.•Fatty acid eutectics have excellent hydrophobic VOC absorption capacities.•Long alkyl chains are ...preferred for hydrophobic VOC capture.•The physical absorption nature of toluene in fatty acid eutectics benefits recovery.•Hydrophobic DESs are promising absorbents for toluene capture in absorption systems.
Emissions of volatile organic compounds (VOCs) are known to be significant human health and ecological risks. Absorption is a classical process applied to eliminate air pollutants, yet the removal efficiency of gaseous contaminants is often curbed by the mass transfer resistance between absorption liquids and hydrophobic VOCs. This work aims to evaluate the feasibility of capturing VOCs from exhaust through the use of hydrophobic deep eutectic solvents (DESs). Among the examined DESs, hydrophobic DESs whose hydrogen bond acceptors (HBAs) and hydrogen bond donors (HBDs) are both fatty acids with long alkyl chains (i.e., decanoic acid DecA and lauric acid LauA) achieve the highest absorption capacity of toluene at 9.94 mg toluene per g DES at 30 °C and 800 ppm toluene with an HBA:HBD molar ratio of 1:3. Hydrophobic interactions between the fatty acids and toluene are critical for improving the VOC absorption ability of DESs, as the toluene solubility increases with an increase in the alkyl chain length of the fatty acid eutectics. The compiled results suggest that effective hydrophobic VOC removal can be realized by the proposed hydrophobic fatty acid eutectics, LauADecA, and the physical absorption nature of toluene in fatty acid eutectics benefits facile recovery and recycling.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To determine the association of prior traumatic brain injury (TBI) with subsequent diagnosis of neurodegeneration disease.
All studies from 1980 to 2016 reporting TBI as a risk factor for diagnoses ...of interest were identified by searching PubMed, Embase, study references, and review articles. The data and study design were assessed by 2 investigators independently. A meta-analysis was performed by RevMan 5.3.
There were 18 studies comprising 3,263,207 patients. Meta-analysis revealed a significant association of prior TBI with subsequent dementia. The pooled odds ratio (OR) for TBI on development of dementia, FTD and TDP-43 associated disease were 1.93 (95% CI 1.47-2.55, p < 0.001), 4.44 (95% CI 3.86-5.10, p < 0.001), and 2.97 (95% CI 1.35-6.53, p < 0.001). However, analyses of individual diagnoses found no evidence that the risk of Alzheimer's disease, and Parkinson's disease in individuals with previous TBI compared to those without TBI.
History of TBI is not associated with the development of subsequent neurodegeneration disease. Care must be taken in extrapolating from these results because no suitable criteria define post TBI neurodegenerative processes. Therefore, further research in this area is needed to confirm these questions and uncover the link between TBI and neurodegeneration disease.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Airborne particulate matter (PM) was collected in Beijing between 24 February and 12 March 2014 to investigate chemical characteristics and potential industrial sources of aerosols along with health ...risk of haze events. Results showed secondary inorganic aerosol was the major contributor to PM2.5 during haze days. Utilizing specific elements, including Fe, La, Tl and As, as fingerprinting tracers, four emission sources, namely iron and steel manufacturing, petroleum refining, cement plant, and coal combustion were explicitly identified; their elevated contributions to PM during haze days were also estimated. The average cancer risk from exposure to inhalable PM toxic metals was 1.53 × 10−4 on haze days, which is one order of magnitude higher than in other developed cities. These findings suggested heavy industries emit large amounts of not only primary PM but also precursor gas pollutants, leading to secondary aerosol formation and harm to human health during haze days.
•Secondary inorganic aerosol is a major contributor to haze formation in Beijing.•Elevated contributions of iron manufacturing, cement plant and petroleum refining to primary PM on haze days are found.•The estimated excess cancer risk due to inhalable PM in Beijing is much higher than in other developed cities around the world.
In this paper, the elevated contributions of iron/steel manufacturing, cement plant and petroleum refining to primary PM on haze days has been quantitatively estimated.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
C1GALT1 controls the crucial step of GalNAc-type O-glycosylation and is associated with both physiologic and pathologic conditions, including cancers. EPH receptors comprise the largest family of ...receptor tyrosine kinases (RTKs) and modulate a diverse range of developmental processes and human diseases. However, the role of C1GALT1 in the signaling of EPH receptors remains largely overlooked. Here, we showed that C1GALT1 high expression in gastric adenocarcinomas correlated with adverse clinicopathologic features and is an independent prognostic factor for poor overall survival. Silencing or loss of C1GALT1 inhibited cell viability, migration, invasion, tumor growth and metastasis, as well as increased apoptosis and cytotoxicity of 5-fluorouracil in AGS and MKN45 cells. Phospho-RTK array and western blot analysis showed that C1GALT1 depletion suppressed tyrosine phosphorylation of EPHA2 induced by soluble Ephrin A1-Fc. O-glycans on EPHA2 were modified by C1GALT1 and both S277A and T429A mutants, which are O-glycosites on EPHA2, dramatically enhanced phosphorylation of Y588, suggesting that not only overall O-glycan structures but also site-specific O-glycosylation can regulate EPHA2 activity. Furthermore, depletion of C1GALT1 decreased Ephrin A1-Fc induced migration and reduced Ephrin A1 binding to cell surfaces. The effects of C1GALT1 knockdown or knockout on cell invasiveness in vitro and in vivo were phenocopied by EPHA2 knockdown in gastric cancer cells. These results suggest that C1GALT1 promotes phosphorylation of EPHA2 and enhances soluble Ephrin A1-mediated migration primarily by modifying EPHA2 O-glycosylation. Our study highlights the importance of GalNAc-type O-glycosylation in EPH receptor-regulated diseases and identifies C1GALT1 as a potential therapeutic target for gastric cancer.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
This retrospective study aimed to determine the short-term efficacy and safety of brolucizumab treatment for recalcitrant neovascular age-related macular degeneration (nAMD) in a real-world setting ...in Taiwan. Recalcitrant nAMD patients who were treated with brolucizumab from November 2021 to August 2022 at Taipei Veterans General Hospital were included. Patients were followed for 3 months after switching to brolucizumab. The primary outcomes were changes in mean best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to the third month. The secondary outcomes included the incidence of intraocular inflammation (IOI), proportion of patients with subretinal and intraretinal fluid (SRF and IRF), and change in pigment epithelial detachment (PED) height from baseline to the third month. The significance level was considered as p < .05 in all tests. A total of 38 patients (40 eyes) with a mean (±SD) age of 76.3 (±10.84) years were included. The baseline BCVA was 0.92±0.64 logMAR, and the CRT and PED height were 329.0±171.18 and 189.8±114.94 um, respectively. The patients had a significant reduction in CRT and resolution of IRF and SRF from baseline to the third month. There were numerical improvements in mean BCVA and PED height, but they were not significant. The percentages of achieving at least 0.1, 0.2, and 0.3 logMAR (equivalent to 5, 10, 15 ETDRS letters) visual gain were 50%, 37.5%, and 30%, respectively, during the first 3 months of follow-up. No IOI occurred in these patients. This study demonstrated that brolucizumab had good short-term structural and functional efficacy in recalcitrant nAMD patients.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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