Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 134
Filter
1.
Molecules ; 29(13)2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38998902

ABSTRACT

Milk thistle is one of the most popular ingredients in the liver protection products market. Silymarin is the main component of milk thistle and contains multiple isomers. There have been few studies focusing on the compositional ratios of silymarin isomers. In this study, we developed an HPLC method for the separation and quantification of silymarin isomers, thereby elucidating their compositional ratios. Through the analysis of more than 40 milk thistle extract products on the market, we found that the ratios, specifically Ratio 1 (the silybin B content to the silybin A content, SBNB/SBNA) and Ratio 2 (the sum of the contents of silybin B and isosilybin B to the sum of the contents of silybin A and isosilybin A, (SBNB + IBNB)/(SBNA + IBNA)), are highly consistent across milk thistle extracts, averaging approximately 1.58 and 1.28, respectively. Furthermore, such ratios were verified in milk thistle seed samples. This study introduces significant findings concerning the stable ratios among silymarin isomers in milk thistle extracts and seeds, thereby offering an innovative approach for quality assurance of milk thistle extracts.


Subject(s)
Flavonolignans , Plant Extracts , Silybin , Silybum marianum , Silymarin , Silybum marianum/chemistry , Chromatography, High Pressure Liquid/methods , Plant Extracts/chemistry , Plant Extracts/analysis , Silymarin/analysis , Silymarin/chemistry , Flavonolignans/analysis , Flavonolignans/chemistry , Silybin/analysis , Silybin/chemistry , Isomerism , Seeds/chemistry
2.
J Ethnopharmacol ; 333: 118430, 2024 Oct 28.
Article in English | MEDLINE | ID: mdl-38857680

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Alpinia officinarum Hance (A. officinarum), a perennial herb known for its medicinal properties, has been used to treat various ailments, such as stomach pain, abdominal pain, emesis, and digestive system cancers. A. officinarum is extensively cultivated in the Qiongzhong and Baisha regions of Hainan, and it holds substantial therapeutic value for the local Li people of Hainan. Kaempferol, a flavonoid derived from A. officinarum, has demonstrated anticancer properties in various experimental and biological studies. Nevertheless, the precise mechanisms through which it exerts its anti-hepatocellular carcinoma (HCC) effects remain to be comprehensively delineated. AIM OF THE STUDY: This investigation aims to elucidate the anti-HCC effects of kaempferol derived from A. officinarum and to delve into its underlying mechanistic pathways. MATERIALS AND METHODS: Using ultra-high performance liquid chromatography-mass spectrometry/mass spectrometry (UPLC-MS/MS) to identify active compounds in A. officinarum. HCCLM3 and Huh7 cells were used to study the anti-HCC effect of kaempferol from A. officinarum. The cytotoxicity and proliferation of kaempferol and A. officinarum were measured using CCK-8 and EDU staining. Wound-healing assays and three-dimensional tumor spheroid models were further used to evaluate migration and the anti-HCC activity of kaempferol. The cell cycle and apoptosis were evaluated by flow cytometry. Western blot and qRT-PCR were used to detect the expression of proteins and genes associated with the cell cycle checkpoints. Finally, bioinformatics was used to analyze the relationship between the differential expression of core targets in the ATM/CHEK2/KNL1 pathway and a poor prognosis in clinical HCC samples. RESULTS: UPLC-MS/MS was employed to detect five active compounds in A. officinarum, such as kaempferol. The CCK-8 and EDU assays showed that kaempferol and A. officinarum significantly inhibited the proliferation of HCC cells. A wound-healing assay revealed that kaempferol remarkably inhibited the migration of HCC cells. Kaempferol significantly suppressed the growth of tumor spheroids. In addition, kaempferol markedly induced G2/M arrest and promoted apoptosis of HCC cells. Mechanically, kaempferol significantly reduced the protein and mRNA expression levels of ATM, CHEK2, CDC25C, CDK1, CCNB1, MPS1, KNL1, and Bub1. Additionally, the combination of kaempferol and the ATM inhibitor KU55933 had a more significant anti-HCC effect. The results of bioinformatics showed that ATM, CHEK2, CDC25C, CDK1, and KNL1 were highly expressed in patients with HCC and cancer tissues, indicating that these genes have certain value in the clinical diagnosis of HCC. CONCLUSIONS: Collectively, our results revealed that kaempferol from A. officinarum inhibits the cell cycle by regulating the ATM/CHEK2/KNL1 pathway in HCC cells. In summary, our research presents an innovative supplementary strategy for HCC treatment.


Subject(s)
Alpinia , Ataxia Telangiectasia Mutated Proteins , Carcinoma, Hepatocellular , Kaempferols , Liver Neoplasms , Kaempferols/pharmacology , Humans , Alpinia/chemistry , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Ataxia Telangiectasia Mutated Proteins/metabolism , Ataxia Telangiectasia Mutated Proteins/genetics , Cell Line, Tumor , G2 Phase Cell Cycle Checkpoints/drug effects , Antineoplastic Agents, Phytogenic/pharmacology , Signal Transduction/drug effects , Cell Proliferation/drug effects , Apoptosis/drug effects
3.
Nat Commun ; 15(1): 4755, 2024 Jun 04.
Article in English | MEDLINE | ID: mdl-38834568

ABSTRACT

Non-alcoholic steatohepatitis (NASH) is a severe type of the non-alcoholic fatty liver disease (NAFLD). NASH is a growing global health concern due to its increasing morbidity, lack of well-defined biomarkers and lack of clinically effective treatments. Using metabolomic analysis, the most significantly changed active lipid sphingosine d18:1 [So(d18:1)] is selected from NASH patients. So(d18:1) inhibits macrophage HIF-2α as a direct inhibitor and promotes the inflammatory factors secretion. Male macrophage-specific HIF-2α knockout and overexpression mice verified the protective effect of HIF-2α on NASH progression. Importantly, the HIF-2α stabilizer FG-4592 alleviates liver inflammation and fibrosis in NASH, which indicated that macrophage HIF-2α is a potential drug target for NASH treatment. Overall, this study confirms that So(d18:1) promotes NASH and clarifies that So(d18:1) inhibits the transcriptional activity of HIF-2α in liver macrophages by suppressing the interaction of HIF-2α with ARNT, suggesting that macrophage HIF-2α may be a potential target for the treatment of NASH.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors , Macrophages , Mice, Knockout , Non-alcoholic Fatty Liver Disease , Sphingosine , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/pathology , Non-alcoholic Fatty Liver Disease/genetics , Animals , Basic Helix-Loop-Helix Transcription Factors/metabolism , Basic Helix-Loop-Helix Transcription Factors/genetics , Male , Macrophages/metabolism , Macrophages/drug effects , Humans , Mice , Sphingosine/analogs & derivatives , Sphingosine/metabolism , Liver/metabolism , Liver/pathology , Liver/drug effects , Mice, Inbred C57BL , Aryl Hydrocarbon Receptor Nuclear Translocator/metabolism , Aryl Hydrocarbon Receptor Nuclear Translocator/genetics , Liver Cirrhosis/metabolism , Liver Cirrhosis/drug therapy , Liver Cirrhosis/pathology , Liver Cirrhosis/genetics , Disease Models, Animal
4.
Org Biomol Chem ; 22(26): 5353-5360, 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38869074

ABSTRACT

The hydroboration and hydrosilylation of alkenes catalyzed by the unsymmetrical ß-diketiminate magnesium methyl complex [(DippXylNacnac)MgMe (THF)] (1) have been reported. When complex 1 was employed as a highly efficient catalyst in the hydroboration of various alkenes with HBpin, only the anti-Markovnikov hydroboration products were obtained in high yields and with high regioselectivities under mild reaction conditions (60 °C). To our surprise, it showed different regioselectivities in the hydrosilylation of a range of alkenes with PhSiH3. Aromatic alkene substrates afforded the corresponding branched Markovnikov hydrosilylation products in high yields and with high regioselectivities; conversely, aliphatic alkenes produced the linear anti-Markovnikov products in moderate yields. This is completely consistent with the corresponding density functional theory (DFT) calculations. In addition, the practical utility was demonstrated via scale-up reactions of boronate esters and a preliminary plausible mechanism of hydroboration and hydrosilylation have been investigated as well.

5.
Semin Cancer Biol ; 101: 58-73, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38810814

ABSTRACT

Cancer is daunting pathology with remarkable breadth and scope, spanning genetics, epigenetics, proteomics, metalobomics and cell biology. Cellular senescence represents a stress-induced and essentially irreversible cell fate associated with aging and various age-related diseases, including malignancies. Senescent cells are characterized of morphologic alterations and metabolic reprogramming, and develop a highly active secretome termed as the senescence-associated secretory phenotype (SASP). Since the first discovery, senescence has been understood as an important barrier to tumor progression, as its induction in pre-neoplastic cells limits carcinogenesis. Paradoxically, senescent cells arising in the tumor microenvironment (TME) contribute to tumor progression, including augmented therapeutic resistance. In this article, we define typical forms of senescent cells commonly observed within the TME and how senescent cells functionally remodel their surrounding niche, affect immune responses and promote cancer evolution. Furthermore, we highlight the recently emerging pipelines of senotherapies particularly senolytics, which can selectively deplete senescent cells from affected organs in vivo and impede tumor progression by restoring therapeutic responses and securing anticancer efficacies. Together, co-targeting cancer cells and their normal but senescent counterparts in the TME holds the potential to achieve increased therapeutic benefits and restrained disease relapse in future clinical oncology.


Subject(s)
Cellular Senescence , Neoplasms , Tumor Microenvironment , Humans , Tumor Microenvironment/drug effects , Neoplasms/drug therapy , Neoplasms/pathology , Neoplasms/metabolism , Cellular Senescence/drug effects , Animals , Antineoplastic Agents/pharmacology , Antineoplastic Agents/therapeutic use , Senescence-Associated Secretory Phenotype , Senotherapeutics/pharmacology
6.
Brief Bioinform ; 25(3)2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38701420

ABSTRACT

The relationship between genotype and fitness is fundamental to evolution, but quantitatively mapping genotypes to fitness has remained challenging. We propose the Phenotypic-Embedding theorem (P-E theorem) that bridges genotype-phenotype through an encoder-decoder deep learning framework. Inspired by this, we proposed a more general first principle for correlating genotype-phenotype, and the P-E theorem provides a computable basis for the application of first principle. As an application example of the P-E theorem, we developed the Co-attention based Transformer model to bridge Genotype and Fitness model, a Transformer-based pre-train foundation model with downstream supervised fine-tuning that can accurately simulate the neutral evolution of viruses and predict immune escape mutations. Accordingly, following the calculation path of the P-E theorem, we accurately obtained the basic reproduction number (${R}_0$) of SARS-CoV-2 from first principles, quantitatively linked immune escape to viral fitness and plotted the genotype-fitness landscape. The theoretical system we established provides a general and interpretable method to construct genotype-phenotype landscapes, providing a new paradigm for studying theoretical and computational biology.


Subject(s)
COVID-19 , Deep Learning , Genotype , Phenotype , SARS-CoV-2 , SARS-CoV-2/genetics , SARS-CoV-2/immunology , Humans , COVID-19/virology , COVID-19/genetics , COVID-19/immunology , Computational Biology/methods , Algorithms , Genetic Fitness
7.
Molecules ; 29(8)2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38675630

ABSTRACT

AHP-3a, a triple-helix acidic polysaccharide isolated from Alpinia officinarum Hance, was evaluated for its anticancer and antioxidant activities. The physicochemical properties and structure of AHP-3a were investigated through gel permeation chromatography, scanning electron microscopy (SEM), Fourier transform infrared spectroscopy, and nuclear magnetic resonance (NMR) spectroscopy. The weight-average molecular weight of AHP-3a was 484 kDa, with the molar percentages of GalA, Gal, Ara, Xyl, Rha, Glc, GlcA, and Fuc being 35.4%, 21.4%, 16.9%, 11.8%, 8.9%, 3.1%, 2.0%, and 0.5%, respectively. Based on the results of the monosaccharide composition analysis, methylation analysis, and NMR spectroscopy, the main chain of AHP-3a was presumed to consist of (1→4)-α-D-GalpA and (1→2)-α-L-Rhap residues, which is a pectic polysaccharide with homogalacturonan (HG) and rhamnogalacturonan-I (RG-I) structural domains containing side chains. In addition, the results of the antioxidant activity assay revealed that the ability of AHP-3a to scavenge DPPH, ABTS, and OH free radicals increased with an increase in its concentration. Moreover, according to the results from the EdU, wound healing, and Transwell assays, AHP-3a can control the proliferation, migration, and invasion of HepG2 and Huh7 hepatocellular carcinoma cells without causing any damage to healthy cells. Thus, AHP-3a may be a natural antioxidant and anticancer component.


Subject(s)
Alpinia , Antioxidants , Biphenyl Compounds , Polysaccharides , Alpinia/chemistry , Polysaccharides/chemistry , Polysaccharides/pharmacology , Polysaccharides/isolation & purification , Humans , Antioxidants/pharmacology , Antioxidants/chemistry , Cell Proliferation/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Hep G2 Cells , Molecular Weight , Cell Line, Tumor , Monosaccharides/analysis , Monosaccharides/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Picrates/chemistry , Picrates/antagonists & inhibitors , Spectroscopy, Fourier Transform Infrared
8.
Poult Sci ; 103(6): 103715, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38652954

ABSTRACT

Eggshell is one of the most important indicators of egg quality, and due to low shell strength, pimple eggs (PE) are more susceptible to breakage, thus causing huge economic losses to the egg industry. At the current time, the molecular mechanisms that regulate the formation of pimple eggs are poorly understood. In this study, uterine tissues of PE-laying hens (n = 8) and normal egg (NE) -laying hens (n = 8) were analyzed by whole transcriptome sequencing, and a total of 619 differentially expressed mRNAs (DE mRNAs), 122 differentially expressed lncRNAs (DE lncRNAs) and 21 differentially expressed miRNAs (DE miRNAs) were obtained. Based on the targeting relationship among DE mRNAs, DE lncRNAs and DE miRNAs, we constructed a competitive endogenous RNA (ceRNA) network including 12 DE miRNAs, 19 DE lncRNAs, and 128 DE mRNAs. Considering the large amount of information contained in the network, we constructed a smaller ceRNA network to better understand the complex mechanisms of pimple egg formation. The smaller ceRNA network network contains 7 DE lncRNAs (LOC107056551, LOC121109367, LOC121108909, LOC121108862, LOC112530033, LOC121113165, LOC107054145), 5 DE miRNAs (gga-miR-6568-3p, gga-miR-31-5p, gga-miR-18b-3p, gga-miR-1759-3p, gga-miR-12240-3p) and 7 DE mRNAs (CABP1, DNAJC5, HCN3, HPCA, IBSP, KCNT1, OTOP3), and these differentially expressed genes may play key regulatory roles in the formation of pimpled eggs in hens. This study provides the overall expression profiles of mRNAs, lncRNAs and miRNAs in the uterine tissues of hens, which provides a theoretical basis for further research on the molecular mechanisms of pimpled egg formation, and has potential applications in improving eggshell quality.


Subject(s)
Chickens , Gene Regulatory Networks , MicroRNAs , Transcriptome , Animals , Chickens/genetics , Chickens/physiology , MicroRNAs/genetics , MicroRNAs/metabolism , Female , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Ovum/physiology , Egg Shell/physiology , Gene Expression Profiling/veterinary , RNA, Competitive Endogenous
9.
BMC Pulm Med ; 24(1): 207, 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38671448

ABSTRACT

OBJECTIVE: The aim of this research was to examine how penehyclidine hydrochloride (PHC) impacts the occurrence of pyroptosis in lung tissue cells within a rat model of lung ischemia-reperfusion injury. METHODS: Twenty-four Sprague Dawley (SD) rats, weighing 250 g to 270 g, were randomly distributed into three distinct groups as outlined below: a sham operation group (S group), a control group (C group), and a test group (PHC group). Rats in the PHC group received a preliminary intravenous injection of PHC at a dose of 3 mg/kg. At the conclusion of the experiment, lung tissue and blood samples were collected and properly stored for subsequent analysis. The levels of malondialdehyde, superoxide dismutase, and myeloperoxidase in the lung tissue, as well as IL-18 and IL-1ß in the blood serum, were assessed using an Elisa kit. Pyroptosis-related proteins, including Caspase1 p20, GSDMD-N, and NLRP3, were detected through the western blot method. Additionally, the dry-to-wet ratio (D/W) of the lung tissue and the findings from the blood gas analysis were also documented. RESULTS: In contrast to the control group, the PHC group showed enhancements in oxygenation metrics, reductions in oxidative stress and inflammatory reactions, and a decrease in lung injury. Additionally, the PHC group exhibited lowered levels of pyroptosis-associated proteins, including the N-terminal segment of gasdermin D (GSDMD-N), caspase-1p20, and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3). CONCLUSION: Pre-administration of PHC has the potential to mitigate lung ischemia-reperfusion injuries by suppressing the pyroptosis of lung tissue cells, diminishing inflammatory reactions, and enhancing lung function. The primary mechanism behind anti-pyroptotic effect of PHC appears to involve the inhibition of oxidative stress.


Subject(s)
Gasdermins , Lung , Pyroptosis , Quinuclidines , Rats, Sprague-Dawley , Reperfusion Injury , Animals , Pyroptosis/drug effects , Reperfusion Injury/drug therapy , Reperfusion Injury/prevention & control , Rats , Quinuclidines/pharmacology , Lung/drug effects , Lung/pathology , Lung/metabolism , Male , Malondialdehyde/metabolism , Disease Models, Animal , Interleukin-1beta/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Interleukin-18/metabolism , Phosphate-Binding Proteins/metabolism , Superoxide Dismutase/metabolism , Peroxidase/metabolism , Oxidative Stress/drug effects , Caspase 1/metabolism , Lung Injury/drug therapy , Lung Injury/metabolism
10.
Gut Microbes ; 16(1): 2334967, 2024.
Article in English | MEDLINE | ID: mdl-38630006

ABSTRACT

Human milk oligosaccharides (HMOs) are vital milk carbohydrates that help promote the microbiota-dependent growth and immunity of infants. Sialic acid (SA) is a crucial component of sialylated milk oligosaccharides (S-MOs); however, the effects of SA supplementation in lactating mothers on S-MO biosynthesis and their breastfed infants are unknown. Probiotic intervention during pregnancy or lactation demonstrates promise for modulating the milk glycobiome. Here, we evaluated whether SA and a probiotic (Pro) mixture could increase S-MO synthesis in lactating mothers and promote the microbiota development of their breastfed neonates. The results showed that SA+Pro intervention modulated the gut microbiota and 6'-SL contents in milk of maternal rats more than the SA intervention, which promoted Lactobacillus reuteri colonization in neonates and immune development. Deficient 6'-SL in the maternal rat milk of St6gal1 knockouts (St6gal1-/-) disturbed intestinal microbial structures in their offspring, thereby impeding immune tolerance development. SA+Pro intervention in lactating St6gal1± rats compromised the allergic responses of neonates by promoting 6'-SL synthesis and the neonatal gut microbiota. Our findings from human mammary epithelial cells (MCF-10A) indicated that the GPR41-PI3K-Akt-PPAR pathway helped regulate 6'-SL synthesis in mammary glands after SA+Pro intervention through the gut - breast axis. We further validated our findings using a human-cohort study, confirming that providing SA+Pro to lactating Chinese mothers increased S-MO contents in their breast milk and promoted gut Bifidobacterium spp. and Lactobacillus spp. colonization in infants, which may help enhance immune responses. Collectively, our findings may help alter the routine supplementation practices of lactating mothers to modulate milk HMOs and promote the development of early-life gut microbiota and immunity.


Subject(s)
Gastrointestinal Microbiome , N-Acetylneuraminic Acid , Female , Infant , Pregnancy , Humans , Animals , Rats , Lactation , Cohort Studies , Phosphatidylinositol 3-Kinases , Milk, Human , Immunity
11.
Sci Rep ; 14(1): 7382, 2024 03 28.
Article in English | MEDLINE | ID: mdl-38548813

ABSTRACT

The structural characteristics of plant communities in urban green spaces have a significant impact on their carbon sequestration function. In this study, comprehensive data were collected from 106 plant communities (each 20 m × 20 m) in Zhengzhou Green Expo Park. We assessed aboveground and soil carbon storage, alongside maintenance carbon emissions, to quantify carbon dynamics. Our primary objective was to establish a statistical model that correlates the structural attributes of plant communities with their total annual carbon sequestration. This model aims to provide a quantitative framework for optimizing community structures to maximize carbon sequestration in urban green spaces. The results showed that density and coverage were significantly and positively correlated with aboveground and soil carbon stocks. Density and mean height were significantly and positively correlated with maintenance carbon emissions. Density played a key structural role in regulating the total carbon sequestration of the plant communities, being 27.24 times more effective than coverage. The total annual carbon sequestration of the plant community reached an optimal value of 327.67 kg CO2-eq/y-1 at a density and cover of 0.15 and 1, respectively. This study provides valuable data for increasing the carbon sink ability of urban green spaces through plant structure regulation and supporting low-carbon development strategies in urban management.


Subject(s)
Carbon Sequestration , Parks, Recreational , Plants , Carbon , Soil/chemistry
12.
J Environ Sci (China) ; 142: 11-20, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38527877

ABSTRACT

Chromium released during municipal solid waste incineration (MSWI) is toxic and carcinogenic. The removal of chromium from simulated MSWI flue gas by four sorbents (CaO, bamboo charcoal (BC), powdered activated carbon (PAC), and Al2O3) and the effects of four oxides (SiO2, Al2O3, Fe2O3, and CaO) on chromium speciation transformation were investigated. The results showed that the removal rates of total Cr by the four sorbents were Al2O3 < CaO < PAC < BC, while the removal rates of Cr(VI) by the four sorbents were Al2O3 < PAC < BC < CaO. CaO had a strong oxidizing effect on Cr(III), while BC and PAC had a better-reducing effect on Cr(VI). SiO2 was better for the reduction of Na2CrO4 and K2CrO4 above 1000°C due to its strong acidity, and the addition of CaO significantly inhibited the reduction of Cr(VI). MgCrO4 decomposed above 700°C to form MgCr2O4, and the reaction between MgCrO4 and oxides also existed in the form of a more stable trivalent spinel. Furthermore, when investigating the effect of oxides on the oxidation of Cr(III) in CrCl3, it was discovered that CaO promoted the conversion of Cr(III) to Cr(VI), while the presence of chlorine caused chromium to exist in the form of Cr(V), and increasing the content of CaO and extending the heating time facilitated the oxidation of Cr(III). In addition, silicate, aluminate, and ferrite were generated after the addition of SiO2, Al2O3, and Fe2O3, which reduced the alkalinity of CaO and had an important role in inhibiting the oxidation of Cr(III). The acidic oxides can not only promote the reduction of Cr(VI) but also have an inhibitory effect on the oxidation of Cr(III) ascribed to alkali metals/alkaline earth metals, and the proportion of acidic oxides can be increased moderately to reduce the generation of harmful substances in the hazardous solid waste heat treatment.


Subject(s)
Oxides , Solid Waste , Silicon Dioxide , Chromium/analysis , Oxidation-Reduction , Incineration
13.
Leukemia ; 38(5): 1003-1018, 2024 May.
Article in English | MEDLINE | ID: mdl-38402368

ABSTRACT

Iron metabolism plays a crucial role in cell viability, but its relationship with adult stem cells and cancer stem cells is not fully understood. The ferritin complex, responsible for intracellular iron storage, is important in this process. We report that conditional deletion of ferritin heavy chain 1 (Fth1) in the hematopoietic system reduced the number and repopulation capacity of hematopoietic stem cells (HSCs). These effects were associated with a decrease in cellular iron level, leading to impaired mitochondrial function and the initiation of apoptosis. Iron supplementation, antioxidant, and apoptosis inhibitors reversed the reduced cell viability of Fth1-deleted hematopoietic stem and progenitor cells (HSPCs). Importantly, leukemic stem cells (LSCs) derived from MLL-AF9-induced acute myeloid leukemia (AML) mice exhibited reduced Fth1 expression, rendering them more susceptible to apoptosis induced by the iron chelation compared to normal HSPCs. Modulating FTH1 expression using mono-methyl fumarate increased LSCs resistance to iron chelator-induced apoptosis. Additionally, iron supplementation, antioxidant, and apoptosis inhibitors protected LSCs from iron chelator-induced cell death. Fth1 deletion also extended the survival of AML mice. These findings unveil a novel mechanism by which ferritin-mediated iron homeostasis regulates the survival of both HSCs and LSCs, suggesting potential therapeutic strategies for blood cancer with iron dysregulation.


Subject(s)
Apoptosis , Hematopoietic Stem Cells , Homeostasis , Iron , Leukemia, Myeloid, Acute , Mitochondria , Neoplastic Stem Cells , Animals , Hematopoietic Stem Cells/metabolism , Hematopoietic Stem Cells/pathology , Mice , Iron/metabolism , Mitochondria/metabolism , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology , Leukemia, Myeloid, Acute/pathology , Leukemia, Myeloid, Acute/metabolism , Leukemia, Myeloid, Acute/genetics , Ferritins/metabolism , Cell Survival , Humans , Mice, Inbred C57BL
14.
Biology (Basel) ; 13(1)2024 Jan 20.
Article in English | MEDLINE | ID: mdl-38275732

ABSTRACT

The decline of Japanese eel (Anguilla japonica) populations in the Yangtze River estuary represents a critical conservation concern. Eleven-years of daily catch data during recruitment periods (i.e., January-April, 2012-2022) indicate that annual catch averaged from 153 to 1108 eels, and show a bimodal pattern in glass eel arrivals. Utilizing seasonal-trend decomposition and generalized additive models, we demonstrated a strong correlation between catch abundance, optimal water temperatures, and lunar cycles. An auto-regressive integrated moving average (ARIMA) model predicts an increase in glass eel numbers for 2023-2024 but also points to a concerning trend of delayed recruitment timing since 2016, attributable to the 0.48 °C per decade rise in sea surface temperatures. This delay correlates with a significant decrease in the average body weight of glass eels, suggesting potential energy deficits that may hinder successful upstream migration. This study not only furthers our understanding of glass eel recruitment dynamics but also underscores the urgent need for targeted conservation measures. Additionally, it highlights the importance of sustained, detailed monitoring to mitigate the detrimental effects of climate change on these eels, vital for preserving the Yangtze River's ecological integrity.

15.
Fitoterapia ; 172: 105730, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37939738

ABSTRACT

Diabetic gastroparesis (DGP) is a common complication of type 2 diabetes mellitus (T2DM). Alpinia officinarum Hance (AOH) is one of the most commonly used both as a food and folk medicines, which is rich in diarylheptanoids and flavonoids. The gastroprotection and hypoglycemic effect make AOH has great potential in developing of anti-DGP complementary medicine. However, the molecular mechanisms of AOH that act against DGP are yet to be elucidated. In this study, we evaluated the therapeutic effects, the potential molecular mechanism, and the changes of gut microbiota of AOH in DGP. The 5 components of the AOH were analyzed, and the potential signaling pathway of AOH improving DGP was predicted by molecular docking. Subsequently, DGP rat model was constructed using high-fat-irregular-diet, AOH intervention significantly reduced blood glucose levels, increased gastrointestinal propulsion rate, and improved gastric histological morphology in DGP rats. Meanwhile, AOH has been shown to regulate the SCF/c-kit signaling pathway and rebalance the gut microbiota, which may be closely related to its role in improving DGP. Taken together, AOH may play a protective role on DGP through multiple mechanisms, which might pave the road for development and utilization of AOH.


Subject(s)
Alpinia , Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Gastroparesis , Rats , Animals , Gastroparesis/drug therapy , Gastroparesis/etiology , Gastroparesis/metabolism , Rats, Sprague-Dawley , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Molecular Docking Simulation , Molecular Structure , Signal Transduction
16.
Int J Biol Macromol ; 254(Pt 2): 127845, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37935292

ABSTRACT

Targeting SHP2 has become a potential cancer treatment strategy. In this study, ellagic acid was first reported as a competitive inhibitor of SHP2, with an IC50 value of 0.69 ± 0.07 µM, and its inhibitory potency was 34.86 times higher that of the positive control NSC87877. Ellagic acid also had high inhibitory activity on the SHP2-E76K and SHP2-E76A mutants, with the IC50 values of 1.55 ± 0.17 µM and 0.39 ± 0.05 µM, respectively. Besides, the IC50 values of ellagic acid on homologous proteins SHP1, PTP1B, and TCPTP were 0.93 ± 0.08 µM, 2.04 ± 0.28 µM, and 11.79 ± 0.83 µM, with selectivity of 1.35, 2.96, and 17.09 times, respectively. The CCK8 proliferation experiment exhibited that ellagic acid would inhibit the proliferation of various cancer cells. It was worth noting that the combination of ellagic acid and KRASG12C inhibitor AMG510 would produce a strong synergistic effect in inhibiting NCI-H358 cells. Western blot experiment exhibited that ellagic acid would downregulate the phosphorylation levels of Erk and Akt in NCI-H358 and MDA-MB-468 cells. Molecular docking and molecular dynamics studies revealed the binding information between SHP2 and ellagic acid. In summary, this study provides new ideas for the development of SHP2 inhibitors.


Subject(s)
Ellagic Acid , Neoplasms , Humans , Ellagic Acid/pharmacology , Molecular Docking Simulation , Neoplasms/drug therapy , Enzyme Inhibitors/chemistry , Phosphorylation
17.
Mar Environ Res ; 194: 106299, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38154196

ABSTRACT

Noise pollution is increasingly prevalent in aquatic ecosystems, causing detrimental effects on growth and behavior of marine fishes. The physiological responses of fish to underwater noise are poorly understood. In this study, we used RNA-sequencing (RNA-seq) to study the transcriptome of the sonic muscle in small yellow croaker (Larimichthys polyactis) after exposure to a 120 dB noise for 30 min. The behavioral experiment revealed that noise exposure resulted in accelerated tail swimming behavior at the beginning of the exposure period, followed by loss of balance at the end of experiment. Transcriptomic analysis found that most highly expressed genes in the sonic muscle, including parvalbumin, slc25a4, and troponin C were related with energy metabolism and locomotor function. Further, a total of 1261 differentially expressed genes (DEGs) were identified, including 284 up-regulated and 977 down-regulated genes in the noise exposure group compared with the control group. Gene ontology (GO) analysis indicated that the most enriched categories of DEGs included protein folding and response to unfolding protein. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis found over-represented pathways including protein processing in the endoplasmic reticulum, chaperones and folding catalysts, as well as arginine and proline metabolism. Specifically, many genes related to fatty acid and collagen metabolism were up-regulated in the noise exposure group. Taken together, our results indicate that exposure to noise stressors alters the swimming behavior of croaker, inducing endoplasmic reticulum stress, disrupting lipid metabolism, and causing collagen degradation in the sonic muscle of L. polyactis.


Subject(s)
Ecosystem , Perciformes , Animals , Gene Expression Profiling/methods , Transcriptome , Muscles , Perciformes/genetics , Collagen/genetics
18.
ACS Appl Eng Mater ; 1(10): 2745-2751, 2023 Oct 27.
Article in English | MEDLINE | ID: mdl-37927948

ABSTRACT

Passive water transport by taking advantage of capillary forces is vital for various applications such as solar-driven interfacial evaporation, evaporative cooling, and atmospheric water harvesting. Surface engineering and structure design with a hydrophilic surface and enhanced capillary force will facilitate passive water transport. Herein, we demonstrate a hydrophilic Cu/CuO foil-based roll for accelerated water transportation. The roll was fabricated by rolling up a typical 2D Cu/CuO film, which transforms the water climbing behavior by significantly enhancing the capillary force between each Cu/CuO film layer. The simple spatial transformation for a 2D film, from planar foil to 3D structure, has extensively facilitated water transportation performance and broadened its practical application potential. The Cu/CuO film with a blade-like nanostructure and excellent hydrophilicity ensures water supply to a limited area, while the capillary effect between different layers of the Cu/CuO foil extends the water transportation height. Consequently, the Cu/CuO foil-based roll demonstrated a high fluidic transport velocity. This design derived from the 2D planar film can be potentially employed for a large range of applications such as evaporating in a confined space and evaporation-driven energy harvest.

19.
BMJ Open ; 13(9): e073332, 2023 09 05.
Article in English | MEDLINE | ID: mdl-37669845

ABSTRACT

OBJECTIVES: Human papillomavirus (HPV) infection is closely associated with cervical cancer, especially the persistent infection of high-risk HPV (HR-HPV) genotypes. Therefore, investigating the HPV prevalence, age-specific, genotype distribution and the impact of the COVID-19 pandemic among large populations was essential for HPV screening and optimising vaccination. DESIGN: This was a cross-sectional study. METHODS: A total of 38 056 cervical epithelial cell specimens were collected in Weifang city from January 2018 to December 2022. The study was divided into seven age groups based on the age of the participants. HPV genotype testing was performed by using a commercial kit which is designed for the detection of 23 HPV genotypes. RESULT: A total of 8998 women were infected with HPV, with an overall positive rate of 23.64% (8998/38 056). Single infection of HPV was dominant among different age groups, which accounted for 71.33% of total infections. The most prevalent genotype was HR-HPV 16 (4.33%), followed by 52, 58, 53 and 68. Low-risk HPV (LR-HPV) 42 exhibited the highest prevalence (2.19%) among six LR-HPV genotypes, representing a novel finding. There was a significant difference in the prevalence across different age groups (p<0.01), with the highest prevalence in the group under 25 years old. During the 3 year COVID-19 breakout period, the number of HPV samples received in 2020, 2021 and 2022 was reduced by 24.03%, 14.79% and 24.76%, respectively. In 2018-2022, the annual prevalence varied between 21.09% and 25.30%, with a decreasing trend, while the prevalence of HR-HPV 39, 56, 31 and LR-HPV 42 increased. CONCLUSION: This study indicates a high-HPV infection rate and age-specific distribution characteristics of HPV genotype infections, as well as analyses of the impact of the COVID-19 outbreak on the HPV prevalence, which provides an epidemiological basis for the control and prevention of HPV infection in this region.


Subject(s)
COVID-19 , Papillomavirus Infections , Humans , Female , Adult , Cross-Sectional Studies , Pandemics , Prevalence , China , Genotype , Papillomaviridae
20.
Opt Express ; 31(16): 26757-26763, 2023 Jul 31.
Article in English | MEDLINE | ID: mdl-37710527

ABSTRACT

A single-frequency quasi-continuous-wave partially end-pumped slab (Innoslab) laser amplifier at 1319 nm was demonstrated. The 3-W single-frequency all-fiber seed laser was amplified to a maximum average power of 80.1 W and the power stability was 0.52% in 10 minutes. The corresponding optical-optical efficiency was 16.1% under absorbed pump power of 478 W. The output pulse width was 131 µs at the repetition of 500 Hz. The beam quality factors of M2 were 1.3 in both the vertical and horizontal directions. To the best of our knowledge, this is the first report on single-frequency Nd:YAG Innoslab amplifier at 1319 nm with such high output power and efficiency.

SELECTION OF CITATIONS
SEARCH DETAIL
...