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1.
Zhongguo Zhong Yao Za Zhi ; 49(15): 4100-4110, 2024 Aug.
Article in Chinese | MEDLINE | ID: mdl-39307742

ABSTRACT

The stem bark of Aquilaria sinensis(Thymelaeaceae), with the local name of "Li-Wa-Zi-Xing", is used in traditional Yi medicine for treating chronic gastritis and other diseases. However, its active ingredients remain currently unknown. In this study, Helicobacter pylori(Hp) is used in anti-bacterial experiments to test the active compounds derived from A. sinensis stem bark. Nineteen compounds were isolated from the stem bark of A. sinensis by column chromatography, high-performance liquid chromatography, recrystallization, etc. Aquilaridiester(1) is a new lignan. The other eighteen compounds were reported before, including docosyl caffeate(2), 6-hydroxy-2-[2-(4-methoxyphenyl)ethyl]-4H-1-benzopyran-4-one(3), qinanone A(4), 6-hydroxy-2-(2-phenylethyl)chromone(5), 6-hydroxy-2-[2-(3-hydroxy-4-methoxyphenyl)ethyl]-4H-1-benzopyran-4-one(6), 6-hydroxy-2-[2-(3-methoxy-4-hydroxyphenyl)ethyl]-4H-1-benzopyran-4-one(7), 6-hydroxy-2-[2-(3,4-dimethoxyphenyl)ethyl]chromone(8), 6-hydroxy-2-[(1E)-2-(4-hydroxy-3-methoxyphenyl)ethenyl]-4H-1-benzopyran-4-one(9), genkwanin(10), 5-hydroxy-2-(4-hydroxy-3,5-dimethoxyphenyl)-7-methoxy-4H-1-benzopyran-4-one(11), 3-hydroxy-1-(4-hydroxy-3,5-dimethoxyphenyl)-1-propanone(12),(+)-syringaresinol(13), zhebeiresinol(14), aquilarin A(15), caruilignan D(16),(-)-ficusal(17), pistaciamide(18), and protocatechuic acid(19). The anti-bacterial results show that compounds 2-7, 10-11, and 13 have inhibitory activity against Hp. Among them, 6-hydroxy-2-(2-phenylethyl)chromone(5) and 6-hydroxy-2-[2-(3-methoxy-4-hydroxyphenyl)ethyl]-4H-benzopyran-4-one(7) have superior inhibitory effects on Hp to others, with the same minimum inhibitory concentration(MIC) of 6.25 µmol·L~(-1). The 2-(2-phenylethyl)chromones are the major active ingredients in A. sinensis stem bark.


Subject(s)
Anti-Bacterial Agents , Helicobacter pylori , Microbial Sensitivity Tests , Plant Bark , Thymelaeaceae , Helicobacter pylori/drug effects , Plant Bark/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Thymelaeaceae/chemistry , Drugs, Chinese Herbal/chemistry , Drugs, Chinese Herbal/pharmacology , Molecular Structure , Plant Stems/chemistry
2.
Food Chem Toxicol ; 193: 114983, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39245401

ABSTRACT

Organic cation transporter 1 (OCT1, gene symbol: SLC22A1) is mainly responsible for the hepatic uptake of various cationic drugs, closely associated with drug-induced liver injury (DILI). Screening and identifying potent OCT1 inhibitors with little toxicity in natural products is of great value in alleviating OCT1-mediated liver injury. Flavonoids, a group of polyphenols commonly found in foodstuffs and herbal products, have been reported to cause transporter-mediated food/herb-drug interactions (FDIs). Our objective was to investigate potential inhibitors of OCT1 from 96 flavonoids, evaluate the hepatoprotective effects on retrorsine-induced liver injury, and clarify the structure-activity relationships of flavonoids with OCT1. Thirteen flavonoids exhibited significant inhibition (>50%) on OCT1 in OCT1-HEK293 cells. Among them, the five strongest flavonoid inhibitors (IC50 < 10 µM), including α-naphthoflavone, apigenin, 6-hydroxyflavone, luteolin, and isosilybin markedly decreased oxaliplatin-induced cytotoxicity. In retrorsine-induced liver injury models, they also reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST) to different levels, the best of which was 6-hydroxyflavone. The pharmacophore model clarified that hydrogen bond acceptors at the 4,8,5' position might play a vital role in the inhibitory effect of flavonoids on OCT1. Taken together, our findings would pave the way to predicting the potential risks of flavonoid-related FDIs in humans and optimizing flavonoid structure to alleviate OCT1-mediated liver injury.

3.
Antioxidants (Basel) ; 13(7)2024 Jul 14.
Article in English | MEDLINE | ID: mdl-39061911

ABSTRACT

Ascorbate peroxidases (APXs) are key components of the ascorbate-glytathione cycle, which plays an important role in removing excess reactive oxygen species (ROS) in plants. Herein, MaAPX1 was verified as being involved in the ripening and senescence of banana fruit, exhibiting responsiveness to the accumulation of ROS and the oxidation of proteins. Site-directed mutation was applied to explore the mechanism of MaAPX1 activity changes. We found that the 32-site cysteine (Cys, C) served as a potential S-nitrosylation site. The mutant MaAPX1C32S activity was decreased significantly when Cys32 was mutated to serine (Ser, S). Intriguingly, the neighboring conserved 36-site methionine (Met, M), which is adjacent to Cys32, displayed an enzyme activity that was approximately five times higher than that of the wild-type MaAPX1 when mutated to lysine (Lys, K). Utilizing LC-MS/MS spectroscopy coupled with stopped-flow analysis showed that the enhanced MaAPX1M36K activity might be due to the increased S-nitrosylation level of Cys32 and the promotion of intermediate (compound I, the first intermediate product of the reaction of APX with H2O2) production. Molecular docking simulations showed that the S-N bond between Cys32 and Lys36 in MaAPX1M36K might have a function in protecting the thiol of Cys32 from oxidation. MaAPX1M36K, a promising mutant, possesses immense potential for improving the antioxidant capabilities of APX in the realm of bioengineering technology research.

4.
J Appl Toxicol ; 44(9): 1388-1402, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38760888

ABSTRACT

Multidrug and toxin extrusion protein 1 (MATE1), an efflux transporter mainly expressed in renal proximal tubules, mediates the renal secretion of organic cationic drugs. The inhibition of MATE1 will impair the excretion of drugs into the tubular lumen, leading to the accumulation of nephrotoxic drugs in the kidney and consequently potentiating nephrotoxicity. Screening and identifying potent MATE1 inhibitors can predict or minimize the risk of drug-induced kidney injury. Flavonoids, a group of polyphenols commonly found in foodstuffs and herbal products, have been reported to cause transporter-mediated food/herb-drug interactions. Our objective was to investigate the inhibitory effects of flavonoids on MATE1 in vitro and in vivo and to assess the effects of flavonoids on cisplatin-induced kidney injury. Thirteen flavonoids exhibited significant transport activity inhibition (>50%) on MATE1 in MATE1-MDCK cells. Among them, the six strongest flavonoid inhibitors, including irisflorentin, silymarin, isosilybin, sinensetin, tangeretin, and nobiletin, markedly increased cisplatin cytotoxicity in these cells. In cisplatin-induced in vivo renal injury models, irisflorentin, isosilybin, and sinensetin also increased serum creatinine and blood urea nitrogen levels to different degrees, especially irisflorentin, which exhibited the most potent nephrotoxicity with cisplatin. The pharmacophore model indicated that the hydrogen bond acceptors at the 3, 5, and 7 positions may play a critical role in the inhibitory effect of flavonoids on MATE1. Our findings provide helpful information for predicting the potential risks of flavonoid-containing food/herb-drug interactions and avoiding the exacerbation of drug-induced kidney injury via MATE1 mediation.


Subject(s)
Cisplatin , Flavonoids , Organic Cation Transport Proteins , Organic Cation Transport Proteins/metabolism , Organic Cation Transport Proteins/antagonists & inhibitors , Animals , Flavonoids/pharmacology , Cisplatin/toxicity , Cisplatin/adverse effects , Herb-Drug Interactions , Male , Dogs , Madin Darby Canine Kidney Cells , Mice , Kidney/drug effects , Kidney/metabolism , Food-Drug Interactions , Acute Kidney Injury/chemically induced , Acute Kidney Injury/prevention & control , Acute Kidney Injury/metabolism
5.
Chem Biodivers ; 21(7): e202400980, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38747266

ABSTRACT

Three new polyhydroxylated spirostanol steroidal saponins, dulongenosides B-D (2-4), along with 14 known compounds, dulongenoside A (1), padelaoside B (5), parisyunnanoside G (6), polyphyllin D (7), ophiopogonin C' (8), formosanin C (9), dioscin (10), paris saponin VII (11), paris H (12), parisyunnanoside I (13), protodioscin (14), proprotogracillin (15), crustecdysone (16), and stigmasterol-3-O-ß-d-glucopyranoside (17), were isolated from the rhizomes of Paris dulongensis (Melanthiaceae). Their chemical structures were elucidated based on extensive analyses of NMR and MS data and acidic hydrolyses. The isolates were evaluated for their cytotoxicity to five human cancer cell lines (HL-60, SW480, MDA-MB-231, A549, and A549/Taxol) and the normal human bronchial epithelial cell line BEAS-2B by the MTS test. Compounds 7-12 and 14 showed cytotoxic activity, with IC50 values ranging from 0.20 to 4.35 µM. Proprotogracillin selectively inhibited A549 (IC50=0.58 µM) and A549/Taxol (IC50=0.74 µM) cells, with no significant cytotoxic activity against HL-60, SW480, MDA-MB-231, or BEAS-2B cells, with IC50 values greater than 40 µM.


Subject(s)
Antineoplastic Agents, Phytogenic , Drug Screening Assays, Antitumor , Melanthiaceae , Rhizome , Saponins , Spirostans , Humans , Saponins/isolation & purification , Saponins/pharmacology , Saponins/chemistry , Rhizome/chemistry , Melanthiaceae/chemistry , Spirostans/chemistry , Spirostans/isolation & purification , Spirostans/pharmacology , Cell Line, Tumor , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/isolation & purification , Cell Proliferation/drug effects , Structure-Activity Relationship , Cell Survival/drug effects , Molecular Structure , Molecular Conformation , Dose-Response Relationship, Drug
6.
Biomater Sci ; 12(8): 2086-2095, 2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38439626

ABSTRACT

Understanding the pharmacokinetic profiles of nanomaterials in living organisms is essential for their application in disease treatment. Bipyramidal DNA frameworks (BDFs) are a type of DNA nanomaterial that have shown prospects in the fields of molecular imaging and therapy. To serve as a reference for disease-related studies involving the BDF, we constructed a 68Ga-BDF and employed positron emission tomography (PET) imaging to establish its pharmacokinetic model in healthy mice. Our investigation revealed that the BDF was primarily eliminated from the body via the urinary system. Ureteral obstruction could significantly alter the metabolism of the urinary system. By utilizing the established pharmacokinetic model, we sensitively observed distinct imaging indicators in unilateral ureteral obstruction and acute kidney injury (a complication of ureteral obstruction) mouse models. Furthermore, we observed that the BDF showed therapeutic effects in an AKI model. We believe that the established pharmacokinetic model and unique renal excretion characteristics of the BDF will provide researchers with more information for studying kidney diseases.


Subject(s)
Acute Kidney Injury , Ureteral Obstruction , Mice , Animals , Ureteral Obstruction/diagnostic imaging , Ureteral Obstruction/complications , Precision Medicine , Kidney/diagnostic imaging , Positron-Emission Tomography , Acute Kidney Injury/diagnostic imaging , Disease Models, Animal
7.
Int J Gynaecol Obstet ; 166(1): 312-325, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38445380

ABSTRACT

OBJECTIVE: To determine and compare the serum metabolites in missed abortion versus normal early pregnancy using ultra-high-performance liquid chromatography and tandem time-of-flight mass spectrometry, and to determine how these metabolites can be used to predict the potential biomarkers and possible metabolic pathways of a missed abortion. METHODS: The serum of patients with a missed abortion was used as the experimental group and the serum of patients with an induced abortion during normal early pregnancy was used as the control group. Principal component analysis and orthogonal partial least square discriminant analysis were additionally used to observe the difference in metabolite distribution between the two groups. A variable weight value (variable importance in the projection; VIP) obtained from the orthogonal partial least squares discriminant analysis model more than 1 and P less than 0.05 were taken to indicate significant differences in metabolite screening. After this, enrichment analysis of the metabolic pathways of these metabolites was conducted using Fisher precise test in order to find the metabolic pathway with the highest correlation with the differential metabolites. RESULTS: In total, 30 patients were included in the experimental group, with 30 patients in the control group. Fifty-five metabolites (VIP > 1, P < 0.05) with significant differences related to missed abortion were selected, among which 35 metabolites increased and 20 decreased in patients with a missed abortion. KEGG pathway enrichment analysis showed that the four metabolic pathways with the highest correlation were cholesterol metabolism, arginine biosynthesis, cell apoptosis, and the FoxO signaling pathway. CONCLUSION: The missed abortion serum metabolites and changes in related metabolic pathways reported in this study provide a basis for the early prediction and diagnosis of a missed abortion.


Subject(s)
Abortion, Missed , Biomarkers , Metabolic Networks and Pathways , Humans , Female , Adult , Pregnancy , Biomarkers/blood , Abortion, Missed/blood , Cross-Sectional Studies , Tandem Mass Spectrometry/methods , Chromatography, High Pressure Liquid/methods , Case-Control Studies , Tertiary Care Centers , Metabolomics/methods
8.
Bioprocess Biosyst Eng ; 47(3): 355-366, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38326513

ABSTRACT

Dyes in wastewater have adverse effects on the environment and human health. Dye-decolorizing peroxidase (DyP) is a promising biocatalyst to dyes degradation, but the decolorization rates varied greatly which influencing factors and mechanisms remain to be fully disclosed. To explore an effective decolorizing approach, we have studied a DyP from Rhodococcus jostii (RhDyPB) which was overexpressed in Escherichia coli to decolorize four kinds of dyes, Reactive blue 19, Eosin Y, Indigo carmine, and Malachite green. We found the decolorization rates of the dyes by purified RhDyPB were all pH-dependent and the highest one was 94.4% of Malachite green at pH 6.0. ESI-MS analysis of intermediates in the decolorization process of Reactive blue 19 proved the degradation was due to peroxidase catalysis. Molecular docking predicated the interaction of RhDyPB with dyes, and a radical transfer reaction. In addition, we performed decolorization of dyes with whole E. coli cell with and without expressing RhDyPB. It was found that decolorization of dyes by E. coli cell was due to both cell absorption and degradation, and RhDyPB expression improved the degradation rates towards Reactive blue 19, Indigo carmine and Malachite green. The effective decolorization of Malachite green and the successful application of whole DyP-overexpressed cells in dye decolorization is conducive to the bioremediation of dye-containing wastewaters by DyPs.


Subject(s)
Anthraquinones , Coloring Agents , Peroxidase , Rhodococcus , Rosaniline Dyes , Humans , Coloring Agents/chemistry , Indigo Carmine , Escherichia coli/genetics , Escherichia coli/metabolism , Molecular Docking Simulation , Peroxidases/chemistry , Oxidoreductases , Wastewater , Biodegradation, Environmental , Catalysis , Hydrogen-Ion Concentration
9.
Sci Rep ; 14(1): 356, 2024 01 03.
Article in English | MEDLINE | ID: mdl-38172506

ABSTRACT

The role of sperm DNA fragmentation index (DFI) in investigating fertility, embryonic development, and pregnancy is of academic interest. However, there is ongoing controversy regarding the impact of DFI on pregnancy outcomes and the safety of offspring in the context of Assisted Reproductive Technology (ART). In this study, we conducted an analysis of clinical data obtained from 6330 patients who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) at the reproductive medical center of The First People's Hospital of Shangqiu and The Affiliated Hospital of Zhengzhou University. The patients was stratified into two distinct groups: IVF group and ICSI group, Within each group, patients were further classified into three subgroups. IVF: group A (< 15%) included 3123 patients, group B (15-30%) included 561 patients, and group C (≥ 30%) included 46 patients. ICSI: group A (< 15%) included 1967 patients, group B (15-30%) included 462 patients, and group C (≥ 30%) included 171 patients. Data were collected and subjected to statistical analysis. There were no significant differences in the basic characteristics among the three groups, and the sperm DFI did not significantly affect the fertilization rates, pregnancy rates, stillbirth rates and the number of birth defects. However, the incidences of miscarriage rates in IVF/ICSI groups with DFI > 30% and DFI 15-30% were significantly higher than those in IVF/ICSI groups with DFI < 15%, and the miscarriage rates in ICSI group with DFI > 30% were significantly higher than DFI 15-30% group, the smooth fitting curve shows that there is a positive correlation between miscarriage rates and sperm DFI (OR 1.095; 95% CI 1.068-1.123; P < 0.001). The birth weight of infants in the IVF/ICSI groups with DFI > 30% and DFI 15-30% exhibited a statistically significant decrease compared to those in the IVF/ICSI groups with DFI < 15%. Furthermore, the birth weight of infants in the ICSI group with DFI > 30% was lower than that of the DFI 15-30% group. The smooth fitting curve analysis demonstrates a negative association between birth weight and sperm DFI (OR 0.913; 95% CI 0.890-0.937; P < 0.001). Sperm DFI has an impact on both miscarriage rates and birth weight in assisted reproductive technology. The smooth fitting curve analysis reveals a positive correlation between miscarriage rates and DFI, while a negative correlation is observed between birth weight and DFI.


Subject(s)
Abortion, Spontaneous , Pregnancy Outcome , Pregnancy , Female , Humans , Male , Abortion, Spontaneous/epidemiology , Abortion, Spontaneous/etiology , Birth Weight , DNA Fragmentation , Semen , Fertilization in Vitro/adverse effects , Spermatozoa , Pregnancy Rate , Retrospective Studies
10.
J Asian Nat Prod Res ; 26(3): 353-371, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37589480

ABSTRACT

The organic anion transporter 3 (OAT3), an important renal uptake transporter, is associated with drug-induced acute kidney injury (AKI). Screening and identifying potent OAT3 inhibitors with little toxicity in natural products, especially flavonoids, in reducing OAT3-mediated AKI is of great value. The five strongest OAT3 inhibitors from the 97 flavonoids markedly decreased aristolochic acid I-induced cytotoxicity and alleviated methotrexate-induced nephrotoxicity. The pharmacophore model clarified hydrogen bond acceptors and hydrophobic groups are the critical pharmacophores. These findings would provide valuable information in predicting the potential risks of flavonoid-containing food/herb-drug interactions and optimizing flavonoid structure to alleviate OAT3-related AKI.


Subject(s)
Acute Kidney Injury , Flavonoids , Organic Anion Transporters, Sodium-Independent , Acute Kidney Injury/drug therapy , Acute Kidney Injury/metabolism , Biological Transport , Flavonoids/pharmacology , Flavonoids/chemistry , Organic Anion Transporters/drug effects , Organic Anion Transporters/metabolism , Structure-Activity Relationship , Organic Anion Transporters, Sodium-Independent/drug effects , Organic Anion Transporters, Sodium-Independent/metabolism
11.
BMC Pregnancy Childbirth ; 23(1): 813, 2023 Nov 23.
Article in English | MEDLINE | ID: mdl-37996795

ABSTRACT

The objective of this study was to investigate the optimal controlled ovarian hyperstimulation (COH) protocol for patients aged 35 and above with poor ovarian response (POR), utilizing real-world data. This retrospective cohort study examined clinical information from a total of 4256 patients between January 2017 and November 2022. The patients were categorized into three groups: modified GnRH agonist protocol (2116 patients), GnRH antagonist protocol (1628 patients), and Mild stimulation protocol (512 patients). Comparative analysis was conducted on clinical variables and pregnancy outcomes across the three groups. The GnRH agonist protocol was associated with a higher number of oocyte number (4.02 ± 2.25 vs. 3.15 ± 1.52 vs. 2.40 ± 1.26, p < 0.001), higher number of transferable embryos (1.73 ± 1.02 vs. 1.35 ± 1.22 vs. 1.10 ± 0.86, p = 0.016), higher cumulative live birth rate 28.50(603/2116) vs. 24.94(406/1628) vs. 20.51(105/512), p < 0.001) than GnRH antagonist protocol and Mild stimulation protocol, the Mild stimulation protocol was associated with a higher miscarriage rates 16.27(62/381) vs. 16.61(48/289) vs. 32.22(29/90), p = 0.001) than the other two groups. Therefore, it can be concluded that all three protocols can be used in patients over 35 years old with poor ovarian response. However, if patients require more frozen-thawed embryo transfers to achieve better cumulative live birth rates, the modified GnRH agonist protocol may be the preferable option.


Subject(s)
Ovarian Hyperstimulation Syndrome , Ovulation Induction , Pregnancy , Humans , Female , Adult , Ovulation Induction/methods , Pregnancy Rate , Retrospective Studies , Gonadotropin-Releasing Hormone , Ovarian Hyperstimulation Syndrome/epidemiology , Ovarian Hyperstimulation Syndrome/etiology , Hormone Antagonists/therapeutic use , Fertilization in Vitro/methods
12.
Zhongguo Zhong Yao Za Zhi ; 48(11): 2981-2988, 2023 Jun.
Article in Chinese | MEDLINE | ID: mdl-37381958

ABSTRACT

Paris rugosa(Melanthiaceae) only grows in Yunnan province of China at present, and its chemical constituents have not been systematically studied. In this study, nine compounds, including one new compound pariposide G(1) and eight known compounds of cerin(2), stigmast-4-en-3-one(3), ß-ecdysone(4), ophiopogonin C'(5), methyl protogracillin(6), gracillin(7), parissaponin H(8), and parisyunnanoside G(9), were isolated and identified from the ethanol extract of P. rugosa rhizomes by column chromatography methods and semi-preparative high-performance liquid chromatography(HPLC). Compounds 1-9 were isolated from this plant for the first time. The antibacterial and antifungal activities of all the compounds were evaluated. The results showed that ophiopogonin C' had strong inhibitory effects on Candida albicans [MIC_(90)=(4.68±0.01) µmol·L~(-1)] and the fluconazole-resistant strain of C. albicans [MIC_(90)=(4.66±0.02) µmol·L~(-1)].


Subject(s)
Liliaceae , Melanthiaceae , Anti-Bacterial Agents , Candida albicans , China , Rhizome
13.
J Appl Toxicol ; 43(10): 1421-1435, 2023 10.
Article in English | MEDLINE | ID: mdl-37057715

ABSTRACT

Organic cation transporter 2 (OCT2) is mainly responsible for the renal secretion of various cationic drugs, closely associated with drug-induced acute kidney injury (AKI). Screening and identifying potent OCT2 inhibitors with little toxicity in natural products in reducing OCT2-mediated AKI is of great value. Flavonoids are enriched in various vegetables, fruits, and herbal products, and some were reported to produce transporter-mediated drug-drug interactions. This study aimed to screen potential inhibitors of OCT2 from 96 flavonoids, assess the nephroprotective effects on cisplatin-induced kidney injury, and clarify the structure-activity relationships of flavonoids with OCT2. Ten flavonoids exhibited significant inhibition (>50%) on OCT2 in OCT2-HEK293 cells. Among them, the six most potent flavonoid inhibitors, including pectolinarigenin, biochanin A, luteolin, chrysin, 6-hydroxyflavone, and 6-methylflavone markedly decreased cisplatin-induced cytotoxicity. Moreover, in cisplatin-induced renal injury models, they also reduced serum blood urea nitrogen (BUN) and creatinine levels to different degrees, the best of which was 6-methylflavone. The pharmacophore model clarified that the aromatic ring, hydrogen bond acceptors, and hydrogen bond donors might play a vital role in the inhibitory effect of flavonoids on OCT2. Thus, our findings would pave the way to predicting the potential risks of flavonoid-containing food/herb-drug interactions in humans and optimizing flavonoid structure to alleviate OCT2-related AKI.


Subject(s)
Acute Kidney Injury , Cisplatin , Humans , Organic Cation Transporter 2/metabolism , Cisplatin/toxicity , Organic Cation Transport Proteins/metabolism , HEK293 Cells , Flavonoids/pharmacology , Structure-Activity Relationship , Acute Kidney Injury/chemically induced , Acute Kidney Injury/prevention & control
14.
Toxicology ; 488: 153475, 2023 04.
Article in English | MEDLINE | ID: mdl-36870413

ABSTRACT

Glucose transporter 1 (GLUT1) is mainly responsible for glucose uptake and energy metabolism, especially in the aerobic glycolysis process of tumor cells, which is closely associated with the advancement of tumors. Numerous studies have demonstrated that the inhibition of GLUT1 can decrease the growth of tumor cells and enhance drug sensitivity, so GLUT1 is considered to be a promising therapeutic target for cancer treatment. Flavonoids are a group of phenolic secondary metabolites present in vegetables, fruits, and herbal products, some of which were reported to increase cancer cells' sensitivity to sorafenib by inhibiting GLUT1. Our objective was to screen potential inhibitors of GLUT1 from 98 flavonoids and assess the sensitizing effect of sorafenib on cancer cells. and illuminate the structure-activity relationships of flavonoids with GLUT1. Eight flavonoids, including apigenin, kaempferol, eupatilin, luteolin, hispidulin, isosinensetin, sinensetin, and nobiletin exhibited significant inhibition (>50%) on GLUT1 in GLUT1-HEK293T cells. Among them, sinensetin and nobiletin showed stronger sensitizing effects and caused a sharp downward shift of the cell viability curves in HepG2 cells, illustrating these two flavonoids might become sensitizers to enhance the efficacy of sorafenib by inhibiting GLUT1. Molecular docking analysis elucidated inhibitory effect of flavonoids on GLUT1 was related to conventional hydrogen bonds, but not Pi interactions. The pharmacophore model clarified the critical pharmacophores of flavonoids inhibitors are hydrophobic groups in 3'positions and hydrogen bond acceptors. Thus, our findings would provide useful information for optimizing flavonoid structure to design novel GLUT1 inhibitors and overcome drug resistance in cancer treatment.


Subject(s)
Flavonoids , Glucose , Humans , Flavonoids/pharmacology , Flavonoids/chemistry , Glucose/metabolism , Glucose Transporter Type 1/metabolism , HEK293 Cells , Molecular Docking Simulation , Sorafenib , Structure-Activity Relationship
15.
Adv Clin Exp Med ; 32(6): 623-631, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36920262

ABSTRACT

INTRODUCTION: According to many reports, multidisciplinary comprehensive care alleviates Parkinson's disease (PD) more frequently than any other standard care, though the results were found to vary greatly. MATERIAL AND METHODS: A systematic literature search up to July 2022 was performed and 1234 related studies were evaluated. The chosen studies comprised 1115 subjects with PD who participated in baseline trials; 633 of them were under multidisciplinary comprehensive care, while 482 were under standard care. Odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (95% CIs) were calculated to measure the results of multidisciplinary comprehensive care for PD by the contentious and dichotomous approaches with a random or fixed influence model employed. RESULTS: The use of multidisciplinary comprehensive care resulted in significantly better health-related quality of life (HRQL) (MD: -3.17; 95% CI: -5.98--0.35, p = 0.03) and Unified Parkinson's Disease Rating Scale (UPDRS) score (MD: -5.25; 95% CI: -10.14--0.37, p = 0.04) compared to the standard care for subjects with PD. Nevertheless, no significant difference was found between multidisciplinary comprehensive care and standard care for subjects with PD regarding medication dosage (MD: 0.31; 95% CI: -0.72-1.34, p = 0.56) and caregiver strain (MD: -0.51; 95% CI: -1.69-0.67, p = 0.40). CONCLUSION: Outpatient multidisciplinary comprehensive care models may improve patient-reported HRQL and UPDRS score; nevertheless, no significant difference was found in terms of medication dosage and caregiver strain compared to the standard care for subjects with PD. The small sample size of 2 out of 7 analyzed studies and the small number of studies in certain comparisons requires attention when analyzing the results.


Subject(s)
Parkinson Disease , Humans , Parkinson Disease/therapy , Parkinson Disease/drug therapy , Quality of Life , Mental Status and Dementia Tests
16.
Phytochemistry ; 207: 113581, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36592859

ABSTRACT

Four undescribed and two known cucurbitane-type triterpenoids, including two heterodimers, elaeocarpudubins A and B, were isolated from the branches of Elaeocarpus dubius (Elaeocarpaceae). The chemical structures of these undescribed isolates were determined by analyses of 1D and 2D NMR and MS data, electronic circular dichroism (ECD) calculations, and chemical transformation. Biogenetically, elaeocarpudubins A and B might be derived from cucurbitacin F through Michael addition with vitamin C and (-)-catechin, respectively. These six isolates were evaluated for their cytotoxic activities against human leukemia HL-60, human lung adenocarcinoma A549, human hepatoma SMMC-7721, human breast cancer MCF-7, human colon cancer SW480, and paclitaxel-resistant A549 (A549/Taxol) cell lines, for their antioxidant properties using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging assay, and for their differentiation effects on nerve growth factor (NGF)-mediated neurite outgrowth in rat pheochromocytoma PC12 cells. Cucurbitacins F (IC50 of 4.98-38.11 µM) and D (IC50 of 0.03-4.40 µM) showed growth-inhibitory activities against these six cancer cell lines. Elaeocarpudubin B (IC50 of 61.04 µM) and elaeocarpudoside B (IC50 of 6.93 µM) showed antioxidant activities. Elaeocarpudubin B and elaeocarpudoside B also showed neurite outgrowth-promoting activities in PC12 cells at a concentration of 10 µM.


Subject(s)
Elaeocarpaceae , Triterpenes , Rats , Animals , Humans , Antioxidants/pharmacology , Molecular Structure , Triterpenes/chemistry , PC12 Cells , Skeleton , Elaeocarpaceae/chemistry
17.
Compr Rev Food Sci Food Saf ; 22(1): 430-450, 2023 01.
Article in English | MEDLINE | ID: mdl-36451298

ABSTRACT

Meat and aquatic products are susceptible to spoilage during distribution, transportation, and storage, increasing the urgency of freshness evaluation. Engineered nanomaterials (ENMs) typically with the diameter in the range of 1-100 nm exhibit fascinating physicochemical properties. ENMs-based sensing systems have received extensive attention for food freshness assessment due to the advantages of being fast, simple, and sensitive. This review focuses on summarizing the recent application of ENMs-based sensing systems for food freshness detection. First, chemical indicators related to the freshness of meat and aquatic products are described. Then, how to apply the ENMs including noble metal nanomaterials, metal oxide nanomaterials, carbon nanomaterials, and metal-organic frameworks for the construction of different sensing systems were described. Besides, the recent advance in ENMs-based colorimetric, fluorescent, electrochemical, and surface-enhanced Raman spectroscopy sensing systems for assessing the freshness of meat and aquatic products were outlined. Finally, the challenges and future research perspectives for the application of ENMs-based sensing systems were discussed. The ENMs-based sensing systems have been demonstrated as effective tools for freshness evaluation. The sensing performance of ENMs employed in different sensing systems depends on their composition, size, shape, and stability of nanoparticles. For the real application of ENMs in food industries, the risks and regulatory issues associated with nanomaterials need to be further considered. With the continuous development of nanomaterials and sensing devices, the ENMs-based sensors are expected to be applied in-field for rapid detection of the freshness of meat and aquatic products in the future.


Subject(s)
Metal-Organic Frameworks , Nanoparticles , Nanostructures , Nanostructures/chemistry , Meat
19.
Article in English | MEDLINE | ID: mdl-36387349

ABSTRACT

Background: This study aimed to explore the clinical efficacy of Chaihu Shugan powder combined with Zu San Li acupoint stimulation on the acute pancreatitis of liver and qi stagnation syndromes, the protection of intestinal barrier function, the prevention of severe tendency, and safety evaluation. Method: Data were collected from October 2019-June 2021 at Xinhua Hospital, which is affiliated with Shanghai Jiao Tong University School of Medicine, Emergency Department. Eighty patients with acute pancreatitis were randomly divided into a control treatment group (40 people) and a combined traditional Chinese medicine (TCM) treatment group (40 people). Detailed records of hospitalised patients were obtained, including the general situation of patients' clinical diagnosis and clinical examination before and after treatment. The changes in inflammatory and immune indexes before and after treatment were recorded. Result: Compared with the standard treatment group, the relief time of abdominal pain in the TCM treatment group was significantly shortened with statistically significant differences. Compared with the standard treatment group, the levels of WBC, ALT, CA, hemodiastase, lipase, TG, and other factors in the TCM treatment group decreased, whereas the levels of DB, SCR, cholesterol, K+, and other factors increased. The differences were statistically significant (P < 0.05). Conclusion: Chaihu Shugan powder combined with Zu San Li acupoint stimulation can reduce the clinical manifestations of liver and qi stagnation syndromes of acute pancreatitis, protect the intestinal barrier function, prevent the tendency of severe illness and improve the prognosis.

20.
Comput Math Methods Med ; 2022: 4381297, 2022.
Article in English | MEDLINE | ID: mdl-35959346

ABSTRACT

Objective: This study is aimed at exploring the effects of the concept of fast-track surgery (FTS) combined with empathic nursing on perioperative complication prevention and postoperative recovery of gynecological malignant tumor patients. Methods: A total of 180 patients with gynecological malignant tumor treated by surgery in our hospital from September 2018 to October 2021 were randomly divided into three groups: group A, group B, and group C, with 60 patients in each group. Group C was given conventional nursing intervention, group B was given FTS intervention, and group A was given FTS intervention combined with empathic care. Psychological stress state (systolic blood pressure, diastolic blood pressure, and heart rate), postoperative recovery indicators (time of first anal exhaust, time of first defecation, time of getting out of bed, and length of postoperative hospital stay), postoperative complications, and psychological state (Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS)) levels of patients in the three groups were compared. Results: Systolic blood pressure, diastolic blood pressure, and heart rate in group A were lower than those in group B, and those in group B were lower than those in group C (all P < 0.05). The time of first anal exhaust, time of first defecation, time of getting out of bed, and postoperative hospital stay in groups A and B were shorter than those in group C (all P < 0.05).The incidence of postoperative complications in groups A and B was 8.33% and 8.33%, respectively, lower than 23.33% in group C (both P < 0.05). SAS and SDS scores of group A were lower than those of groups B and C after intervention (all P < 0.05). Conclusion: The concept of FTS combined with empathic nursing is beneficial to reduce the stress response of patients with gynecological malignant tumor before surgery, reduce the risk of postoperative complications, improve patients' mood, and speed up the rehabilitation process of patients.


Subject(s)
Postoperative Complications , Stomach Neoplasms , Humans , Length of Stay , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Postoperative Complications/prevention & control , Postoperative Period
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