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1.
Am J Physiol Gastrointest Liver Physiol ; 327(4): G485-G498, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39259911

RESUMO

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a prevalent chronic liver condition worldwide, demanding further investigation into its pathogenesis. Circular RNAs (circRNAs) are emerging as pivotal regulators in MASLD processes, yet their pathological implications in MASLD remain poorly understood. This study focused on elucidating the role of circular RNA ribonucleotide reductase subunit M2 (circRRM2) in MASLD progression. In this study, we used both in vitro and in vivo MASLD models using long-chain-free fatty acid (FFA)-treated hepatocytes and high-fat diet (HFD)-induced MASLD in mice, respectively. We determined the expression patterns of circRRM2, microRNA-142-5p (miR-142-5p), and neuregulin 1 (NRG1) in livers of MASLD-afflicted mice and MASLD hepatocytes by RT-qPCR. Dual-luciferase reporter assays verified the binding relationships among circRRM2, miR-142-5p, and NRG1. We conducted further analyses of their roles in MASLD hepatocytes and modulated circRRM2, miR-142-5p, and NRG1 expression in vitro by transfection. Our findings were validated in vivo. The results demonstrated reduced levels of circRRM2 and NRG1, along with elevated miR-142-5p expression in MASLD livers and hepatocytes. Overexpression of circRRM2 downregulated lipogenesis-related genes and decreased triglycerides accumulation in livers of MASLD mice. MiR-142-5p, which interacts with circRRM2, effectively counteracted the effects of circRRM2 in MASLD hepatocytes. Furthermore, NRG1 was identified as a miR-142-5p target, and its overexpression mitigated the regulatory impact of miR-142-5p on MASLD hepatocytes. In conclusion, circRRM2, via its role as a miR-142-5p sponge, upregulating NRG1, possibly influenced triglycerides accumulation in both in vitro and in vivo MASLD models.NEW & NOTEWORTHY CircRRM2 expression was downregulated in free fatty acid (FFA)-challenged hepatocytes and high-fat diet (HFD) fed mice. Overexpressed circular RNA ribonucleotide reductase subunit M2 (circRRM2) attenuated metabolic dysfunction-associated steatotic liver disease (MASLD) development by suppressing FFA-induced triglycerides accumulation. CircRRM2 targeted microRNA-142-5p (miR-142-5p), which served as an upstream inhibitor of neuregulin 1 (NRG1) and collaboratively regulated MASLD progression.


Assuntos
Dieta Hiperlipídica , Hepatócitos , MicroRNAs , Neuregulina-1 , RNA Circular , Animais , MicroRNAs/metabolismo , MicroRNAs/genética , Camundongos , Hepatócitos/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Masculino , Neuregulina-1/genética , Neuregulina-1/metabolismo , Camundongos Endogâmicos C57BL , Fígado Gorduroso/metabolismo , Fígado Gorduroso/genética , Humanos , Fígado/metabolismo , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Ribonucleosídeo Difosfato Redutase
2.
Anal Methods ; 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39292521

RESUMO

The intrinsic fluorescence of berberine is very weak, which can be enhanced by its interaction with specific aptamers. A simple and sensitive DNA sensor for visual detection of berberine has here been established. When using this sensor, there was a good linear relationship between the change in fluorescence intensity of berberine and the concentration of berberine in the range of 16-2000 nM, with a detection limit of 5.1 nM. The change in fluorescence intensity was caused by the addition of aptamers. A detection limit of 170.1 nM was acquired by reading the RGB values of fluorescent images with a smartphone for the quantification of berberine. Common antibiotics did not interfere with the measurement of the berberine concentration. The molecular ion peaks of the complexes formed by the aptamer and berberine could be clearly observed by electrospray ionization mass spectrometry. The UV-vis absorption spectra, circular dichroism spectra, and fluorescence spectra indicated a strong interaction between berberine and the aptamer. The dissociation constant (Kd) between berberine and the aptamer was 1.91 µM. This sensor was both simple and sensitive, requiring only a 21-base oligonucleotide. It realized a visual quantitative analysis with a smartphone. This method could also be used for similar fluorescence visualization determination of aptamer-based drug molecules.

3.
Cell Regen ; 13(1): 16, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-39101982

RESUMO

Organs-on-chips are microphysiological systems that allow to replicate the key functions of human organs and accelerate the innovation in life sciences including disease modeling, drug development, and precision medicine. However, due to the lack of standards in their definition, structural design, cell source, model construction, and functional validation, a wide range of translational application of organs-on-chips remains a challenging. "Organs-on-chips: Intestine" is the first group standard on human intestine-on-a-chip in China, jointly agreed and released by the experts from the Chinese Society of Biotechnology on 29th April 2024. This standard specifies the scope, terminology, definitions, technical requirements, detection methods, and quality control in building the human intestinal model on a chip. The publication of this group standard will guide the institutional establishment, acceptance and execution of proper practical protocols and accelerate the international standardization of intestine-on-a-chip for translational applications.

4.
Arch Med Res ; 56(1): 103072, 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39208548

RESUMO

BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease (AD), that receives less attention compared to rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and primary Sjögren's syndrome (pSS). This study aims to analyze transcriptional profiles and immune cell composition in peripheral blood mononuclear cells (PBMC) from SSc patients compared to other ADs. METHODS: RNA-seq data from 119 untreated patients (eight with SSc, 42 with RA, 41 with pSS, 28 with SLE) and 20 healthy controls were analyzed. Bioinformatics tools were employed to identify differentially expressed genes (DEGs), biological functions and immune cell profiles unique to SSc and shared with other ADs. RESULTS: 1,148 DEGs were found in SSc, with upregulated genes associated with megakaryocyte processes and downregulated genes associated with neutrophil function and immune response. DEGs, including ALDH1A1 and MEGF9, were associated with neutropenia. Upregulated transcription factors (TFs) were linked to embryonic hematopoiesis and downregulated TFs were involved in leukocyte differentiation and immune regulation. Comparative analysis with other ADs revealed common pathogenic pathways, emphasizing megakaryocyte proliferation. Neutrophils count was significantly decreased in ADs (p < 0.001) compared to healthy controls. Comparative analysis highlighted common pathways, particularly in megakaryocyte proliferation, and unique genes (MEGF9, MMP8, and KRT family members) in SSc, suggesting roles in neutrophil function, skin integrity, and fibrosis. CONCLUSIONS: This study identifies dysregulated gene expression (KRT and MMP8) associated with neutrophil function and increased megakaryocytes in SSc, highlighting common patterns across autoimmune diseases. These findings offer new insights into the potential pathogenesis of SSc, and help to explore new targets for the treatment.

5.
Front Endocrinol (Lausanne) ; 15: 1387845, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39157680

RESUMO

Background: Thyroid hormones significantly influence cardiovascular pathophysiology, yet their prognostic role in acute aortic dissection (AAD) remains inadequately explored. This study assesses the prognostic value of thyroid hormone levels in AAD, focusing on the mediating roles of renal function and coagulation. Methods: We included 964 AAD patients in this retrospective cohort study. Utilizing logistic regression, restricted cubic splines, and causal mediation analysis, we investigated the association between thyroid hormones and in-hospital mortality and major adverse cardiovascular events (MACEs). Results: In AAD patients overall, an increase of one standard deviation in FT4 levels was associated with a 31.9% increased risk of MACEs (OR 1.319; 95% CI 1.098-1.584) and a 36.1% increase in in-hospital mortality (OR 1.361; 95% CI 1.095-1.690). Conversely, a higher FT3/FT4 ratio was correlated with a 20.2% reduction in risk of MACEs (OR 0.798; 95% CI 0.637-0.999). This correlation was statistically significant predominantly in Type A AAD, while it did not hold statistical significance in Type B AAD. Key renal and coagulation biomarkers, including blood urea nitrogen, creatinine, cystatin C, prothrombin time ratio, prothrombin time, and prothrombin time international normalized ratio, were identified as significant mediators in the interplay between thyroid hormones and MACEs. The FT3/FT4 ratio exerted its prognostic influence primarily through the mediation of renal functions and coagulation, while FT4 levels predominantly impacted outcomes via a partial mediation effect on coagulation. Conclusion: FT4 levels and the FT3/FT4 ratio are crucial prognostic biomarkers in AAD patients. Renal function and coagulation mediate the association between the thyroid hormones and MACEs.


Assuntos
Dissecção Aórtica , Coagulação Sanguínea , Hormônios Tireóideos , Humanos , Masculino , Feminino , Prognóstico , Estudos Retrospectivos , Pessoa de Meia-Idade , Hormônios Tireóideos/sangue , Coagulação Sanguínea/fisiologia , Dissecção Aórtica/sangue , Dissecção Aórtica/fisiopatologia , Rim/fisiopatologia , Idoso , Biomarcadores/sangue , Mortalidade Hospitalar , Adulto , Doença Aguda
6.
Plants (Basel) ; 13(14)2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39065503

RESUMO

Drought is one of the most hazardous environmental factors due to its severe damage on plant growth, development and productivity. Plants have evolved complex regulatory networks and resistance strategies for adaptation to drought stress. As a conserved epigenetic regulation, DNA methylation dynamically alters gene expression and chromosome interactions in plants' response to abiotic stresses. The development of omics technologies on genomics, epigenomics and transcriptomics has led to a rapid increase in research on epigenetic variation in non-model crop species. In this review, we summarize the most recent findings on the roles of DNA methylation under drought stress in crops, including methylating and demethylating enzymes, the global methylation dynamics, the dual regulation of DNA methylation on gene expression, the RNA-dependent DNA methylation (RdDM) pathway, alternative splicing (AS) events and long non-coding RNAs (lnc RNAs). We also discuss drought-induced stress memory. These epigenomic findings provide valuable potential for developing strategies to improve crop drought tolerance.

7.
J Basic Microbiol ; 64(7): e2400103, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38771080

RESUMO

This study aimed to enhance extracellular polysaccharide (EPS) production in Cordyceps militaris by constructing a quorum sensing (QS) system to regulate the expression of biosynthetic enzyme genes, including phosphoglucomutase, hexokinase, phosphomannomutase, polysaccharide synthase, and UDP-glucose 4-epimerase genes. The study found higher EPS concentrations in seven recombinant strains compared to the wild-type C. militaris, indicating that the overexpression of key enzyme genes increased EPS production. Among them, the CM-pgm-2 strain exhibited the highest EPS production, reaching a concentration of 3.82 ± 0.26 g/L, which was 1.52 times higher than the amount produced by the wild C. militaris strain. Additionally, the regulatory effects of aromatic amino acids on the QS system of the CM-pgm-2 strain were investigated. Under the influence of 45 mg/L tryptophan, the EPS production in CM-pgm-2 reached 4.75 ± 0.20 g/L, representing a 1.90-fold increase compared to wild C. militaris strains. This study provided an effective method for the large-scale production of EPSs in C. militaris, and opened up new avenues for research into fungal QS mechanisms.


Assuntos
Cordyceps , Percepção de Quorum , Cordyceps/genética , Cordyceps/metabolismo , Cordyceps/crescimento & desenvolvimento , Polissacarídeos/metabolismo , Polissacarídeos/biossíntese , Regulação Fúngica da Expressão Gênica , Polissacarídeos Fúngicos/biossíntese , Polissacarídeos Fúngicos/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Triptofano/metabolismo , Triptofano/biossíntese
8.
Heliyon ; 10(9): e29934, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38707356

RESUMO

Background: Managing systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) is pivotal in acute aortic dissection (AAD) care. However, no prior studies have jointly analyzed the trajectories of these parameters. This research aimed to characterize their joint longitudinal trajectories and investigate the influence on AAD prognosis. Methods: We included AAD patients from the Medical Information Mart for Intensive Care (MIMIC)-IV database. Using group-based multi-trajectory modeling (GBMTM), we identified combined trajectories of SBP, DBP, and HR within the initial 24 h of intensive care unit (ICU) admission. Cox proportional hazard regression, log-binomial regression, and logistic regression were employed to assess the association between trajectory groups and mortality outcomes. Results: Data from 337 patients were analyzed. GBMTM identified five combined trajectory groups. Group 1 featured rapidly declining SBP and DBP with high pulse pressure and low HR; Group 2 showed high to moderate SBP with slight rebound and persistently low HR; Group 3 displayed persistently moderate BP and HR; Group 4 was characterized by moderate blood pressure with persistently high HR; and Group 5 had high to moderate SBP with slight rebound, high but gradually declining DBP, and slightly high HR. Group 3 demonstrated a lower risk of mortality, with an adjusted hazard ratio of 0.32 (95 % CI, 0.14-0.74), and the adjusted relative risks for in-hospital, 30-day, and 1-year mortalities were 0.37 (95 % CI, 0.15-0.87), 0.25 (95 % CI, 0.10-0.62), and 0.41 (95 % CI, 0.22-0.79), respectively. The time-independent C-index curve demonstrated that the multi-trajectory groups had higher C-index values than any univariate trajectory groups or admission values of SBP, DBP, and HR. Conclusions: Utilization of GBMTM can yield data-driven insights to identify distinct subphenotypes in AAD patients. The combined trajectories of SBP, DBP, and HR within 24 h of ICU admission significantly influenced the mortality rate.

9.
Oncoimmunology ; 13(1): 2355684, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38798746

RESUMO

Identifying tumor-relevant T cell subsets in the peripheral blood (PB) has become a potential strategy for cancer treatment. However, the subset of PB that could be used to treat cancer remains poorly defined. Here, we found that the CX3CR1+ T cell subset in the blood of patients with lung cancer exhibited effector properties and had a higher TCR matching ratio with tumor-infiltrating lymphocytes (TILs) compared to CX3CR1- T cells, as determined by paired single-cell RNA and TCR sequencing. Meanwhile, the anti-tumor activities, effector cytokine production, and mitochondrial function were enhanced in CX3CR1+ T cells both in vitro and in vivo. However, in the co-culture system of H322 cells with T cells, the percentages of apoptotic cells and Fas were substantially higher in CX3CR1+ T cells than those in CX3CR1- T cells. Fas-mediated apoptosis was rescued by treatment with an anti-PD-1 antibody. Accordingly, the combination of adoptive transfer of CX3CR1+ T cells and anti-PD-1 treatment considerably decreased Fas expression and improved the survival of lung xenograft mice. Moreover, an increased frequency of CX3CR1+ T cells in the PB correlated with a better response and prolonged survival of patients with lung cancer who received anti-PD-1 therapy. These findings indicate the promising potential of adoptive transfer of peripheral CX3CR1+ T cells as an individual cancer immunotherapy.


Assuntos
Receptor 1 de Quimiocina CX3C , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Linfócitos do Interstício Tumoral , Receptor de Morte Celular Programada 1 , Animais , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Receptor 1 de Quimiocina CX3C/metabolismo , Humanos , Camundongos , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/efeitos dos fármacos , Linfócitos do Interstício Tumoral/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Linhagem Celular Tumoral , Feminino , Apoptose/efeitos dos fármacos , Masculino , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/metabolismo , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo
10.
Nat Prod Res ; : 1-5, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38646779

RESUMO

Penicillium macrosclerotiorum was isolated for the first time from the leaves of Ilex pubescens Hook. et Arn (VSN-2022-03-18-001) and found to produce bioactive compounds. Seven compounds were obtained from the fermentation broth and mycelia of P. macrosclerotiorum and identified as palmitic acid (1), methyl 6-acetyl-5,7,8-trihydroxy-4-methoxy-2-naphthoate (2), ergosterol (3), daidzein (4), oleuropein (5), pedunculoside (6) and acteoside (7). Compounds 3, 4 and 7 exhibited antioxidant activity against diphenyl picryl hydrazinyl with IC50 values of 58.06, 2.58 and 12.01 µg/mL, respectively. Compounds 3, 5 and 7 exhibit inhibitory activity against Escherichia coli with MIC values of 0.78, 3.13 and 3.13 mg/mL, while compounds 2, 3, 4, 5, 6 and 7 exhibited inhibitory effect on Candida albicans with MIC values of 0.20, 0.20, 0.39, 0.63, 0.78 and 0.78 mg/mL, respectively. Furthermore, Compound 4 effectively inhibited HepG2 cells, showing an IC50 of 34.03 µg/mL.

11.
Environ Res ; 252(Pt 1): 118794, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38555087

RESUMO

The Tibetan Plateau (TP) constitutes a fragile and sensitive ecological environment, which is vulnerable to global climate change and human activities. To investigate the anthropogenic effects on the TP's environmental system is valuable for guiding human responses and adaptations to future environmental changes. In this study, we detailedly analyzed the geochemical elements of four representative soil sections developed on loess from Ganzi, Jinchuan, Aba, and Chuanzhusi in the eastern TP. The chemical elemental profiles distinctly indicated the presence of typical anthropogenic elements (Cu, Zn, Ni, Cr, Pb, Mn, and Fe), underscoring the substantial influence of human activities on TP soil, and showing spatial variance. Our results indicate that anthropogenic impacts were relatively low at Aba and Ganzi, resulting in a deficit of anthropogenic elements at the surface layer. Whereas at Jinchuan and Chuanzhusi, relatively intense anthropogenic impacts have led to the enrichment of anthropogenic elements in the topsoil. We infer that agricultural activities, increased traffic, and expansion of tourism activities were the major factors affecting the anthropogenic elements of TP soils. Our study highlights the impact of human activities on soil geochemical processes in the Tibetan Plateau.


Assuntos
Monitoramento Ambiental , Poluentes do Solo , Solo , Tibet , Solo/química , Poluentes do Solo/análise , Atividades Humanas , Humanos , Metais Pesados/análise
12.
Heliyon ; 10(4): e26045, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38390087

RESUMO

When employing the open stope mining method for extracting materials in underground mines, it is necessary for personnel and equipment to operate within a specified range of the goaf area, thus, adoption of appropriate mining parameters in the mining field is crucial for promoting safe production practices. In this study, the Harazi iron mine is taken as the research subject, with theoretical analysis combined with numerical simulation that enables the authors to simulate and analyze the width parameter of the mining field. Theoretical analysis utilizing the Matthew stability chart method confirms that the width of the mining field in Harazi iron mine should not exceed 9 m. Based on this finding, the mechanical response characteristics accompanying the mining process at different widths within the mining field limits are analyzed via the Flac3D numerical analysis software. As a result of this analysis, the optimal width of the mining field in Harazi iron mine is determined to be 8 m. The method utilized in this article provides a rational approach to determining structural parameters of the mining field and can effectively aid in promoting mine safety practices.

13.
Bioorg Chem ; 143: 107055, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38185008

RESUMO

Hydration, a secondary activity mediated by nitrilase, is a promising new pathway for amide production. However, low hydration activity of nitrilase or trade-off between hydration and catalytic activity hinders its application in the production of amides. Here, natural C-terminal-truncated wild-type nitrilase, mined from a public database, obtained a high-hydration activity nitrilase as a novel evolutionary starting point for further protein engineering. The nitrilase Nit-74 from Spirosoma linguale DSM 74 was successfully obtained and exhibited the highest hydration activity level, performing 50.7 % nicotinamide formation and 87.6 % conversion to 2 mM substrate 3-cyanopyridine. Steric hindrance of the catalytic activity center and the N-terminus of the catalytic cysteine residue helped us identify three key residues: I166, W168, and T191. Saturation mutations resulted in three single mutants that further improved the hydration activity of N-heterocyclic nitriles. Among them, the mutant T191S performed 72.7 % nicotinamide formation, which was much higher than the previously reported highest level of 18.7 %. Additionally, mutants I166N and W168Y exhibited a 97.5 % 2-picolinamide ratio and 97.7 % isonicotinamide ratio without any loss of catalytic activity, which did not indicate a trade-off effect. Our results expand the screening and evolution library of promiscuous nitrilases with high hydration activity for amide formation.


Assuntos
Aminoidrolases , Cytophagaceae , Nitrilas , Pirimidinas , Triazóis , Nitrilas/química , Aminoidrolases/genética , Aminoidrolases/química , Aminoidrolases/metabolismo , Amidas , Niacinamida , Especificidade por Substrato
14.
Biotechnol Lett ; 45(8): 993-1000, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37243776

RESUMO

The self-sufficient cytochrome P450 BM3 mutant (A74G/F87V/D168H/L188Q) can serve as a biocatalyst for whole-cell catalysis process of indigo. Nevertheless, the bioconversion yield of indigo is generally low under normal cultivation conditions (37 °C, 250 rpm). In this study, a recombinant E. coli BL21(DE3) strain was constructed to co-express the P450 BM3 mutant gene and GroEL/ES genes to investigate whether GroEL/ES can promote the indigo bioconversion yield in E. coli. The results revealed that the GroEL/ES system could significantly increase the indigo bioconversion yield, and the indigo bioconversion yield of the strain co-expressing P450 BM3 mutant and GroEL/ES was about 21-fold that of the strain only expressing the P450 BM3 mutant. In addition, the P450 BM3 enzyme content and in vitro indigo bioconversion yield were determined to explore the underlying mechanism for the improvement of indigo bioconversion yield. The results revealed that GroEL/ES did not increase indigo bioconversion yield by increasing the content of P450 BM3 enzyme and its enzymatic transformation efficiency. Moreover, GroEL/ES could improve the intracellular nicotinamide adenine dinucleotide phosphate (NADPH)/NADP+ ratio. Given that NADPH is an important coenzyme in the catalytic process of indigo, the underlying mechanism for the improvement of indigo bioconversion yield is probably related to an increase in the intracellular NADPH/NADP+ ratio.


Assuntos
Escherichia coli , Índigo Carmim , Escherichia coli/genética , Escherichia coli/metabolismo , NADP/metabolismo , NADPH-Ferri-Hemoproteína Redutase/genética , NADPH-Ferri-Hemoproteína Redutase/metabolismo , Proteínas de Bactérias/metabolismo , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Biotransformação
15.
Sci Rep ; 13(1): 4528, 2023 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-36941308

RESUMO

Red ginseng has been used in traditional medicine for centuries in Asia. In this study, we evaluated four types of red ginseng grown in different areas (Chinese red ginseng, Korean red ginseng A, Korean red ginseng B, and Korean red ginseng C) for their ability to inhibit lung tumor formation and growth induced by the carcinogen benzo(a)pyrene (B(a)P) in A/J mice and found that Korean red ginseng B was the most effective at lowering the tumor load among the four red ginseng varieties. Moreover, we analyzed the levels of various ginsenosides (Rg1, Re, Rc, Rb2, Rb3, Rb1, Rh1, Rd, Rg3, Rh2, F1, Rk1, and Rg5) in four kinds of red ginseng extract and found that Korean red ginseng B had the highest level of ginsenoside Rg3 (G-Rg3), which suggested that G-Rg3 may play an important role in its therapeutic efficacy. This work revealed that the bioavailability of G-Rg3 was relatively poor. However, when G-Rg3 was coadministered with verapamil, a P-glycoprotein inhibitor, the G-Rg3 efflux in Caco-2 cells was lowered, the small intestinal absorption rate of G-Rg3 in the rat models was increased, the concentration levels of G-Rg3 were elevated in the intestine and plasma, and its tumor-preventive abilities in the tumorigenesis rat model induced by B(a)P were also augmented. We also found that G-Rg3 reduced B(a)P-induced cytotoxicity and DNA adduct formation in human lung cells and rescued phase II enzyme expression and activity through Nrf2 pathways, which may be the potential mechanisms underlying the inhibitory effects of G-Rg3 on lung tumorigenesis. Our study showed a potentially vital role of G-Rg3 in targeting lung tumors in murine models. The oral bioavailability of this ginsenoside was augmented by targeting P-glycoprotein, which allowed the molecule to exert its anticancer effects.


Assuntos
Ginsenosídeos , Panax , Ratos , Humanos , Camundongos , Animais , Ginsenosídeos/farmacologia , Benzo(a)pireno/toxicidade , Células CACO-2 , Carcinogênese , Pulmão , Subfamília B de Transportador de Cassetes de Ligação de ATP
16.
World J Surg Oncol ; 21(1): 45, 2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36782320

RESUMO

BACKGROUND: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) is still under investigation as adjuvant treatment for early-stage disease. Here, we performed a meta-analysis to evaluate the efficacy of adjuvant EGFR-TKI versus non-EGFR-TKI treatment in patients with completely resected non-small cell lung cancer (NSCLC) harboring EGFR mutation. METHODS: Two investigators independently extracted data from databases. A meta-analysis was performed following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. The protocol was registered in PROSPERO (ID: CRD42022316481). The primary outcome was disease-free survival (DFS) in patients with EGFR mutation, measured as the hazard ratio (HR). Other outcomes (of subgroup analyses) included overall survival (OS) and DFS. RESULTS: After the systematic screening, eight studies with a total of 3098 patients with stage IB-IIIA NSCLC were included. The results show that in patients with EGFR mutation, the DFS in the adjuvant EGFR-TKI group was significantly superior to that in the control group, with a HR of 0.47 (95% confidence interval [CI]: 0.30-0.74; P = 0.001). In subgroup analyses of DFS, the benefit was observed in the EGFR-TKI group versus the chemotherapy group (HR 0.50, 95% CI 0.30-0.84; P = 0.009), the EGFR-TKI combined with chemotherapy group versus the chemotherapy group (HR 0.37, 95% CI 0.16-0.85; P = 0.02), and in stage IIA-IIIA NSCLC (HR 0.45, 95% CI 0.27-0.74; P = 0.002). However, the benefit of DFS did not translate into improved OS in the whole population (HR 0.79, 95% CI 0.54-1.14; P = 0.20). CONCLUSION: EGFR-TKIs prolonged DFS but not OS in patients with completely resected stage II-IIIA NSCLC harboring EGFR mutation. Longer follow-ups and new clinical trials that can result in changes in clinical practice are needed.


Assuntos
Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Receptores ErbB , Neoplasias Pulmonares , Humanos , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Receptores ErbB/antagonistas & inibidores , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Mutação , Ensaios Clínicos Controlados Aleatórios como Assunto , /uso terapêutico
17.
Fitoterapia ; 165: 105388, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36496050

RESUMO

Two previously undescribed amino acid-type alkaloids with unusual N-pyridinium cation (1-2) and six known alkaloids (3-8), were isolated from the roots and rhizomes of Sophora tonkinensis Gapnea. Their structures were characterized by UV, IR, NMR, and HRESIMS spectroscopic data. The absolute configurations of compounds 1 and 2 were established through comparison of their experimental ECD spectra to the theoretical spectra of 2 calculated by TDDFT method. The plausible biosynthetic pathway of pyridinium was also proposed. Moreover, compound 4 exhibited weak XOD inhibitory activity with the inhibition rate of 65.8% at concentration of 10 µM.


Assuntos
Alcaloides , Sophora , Rizoma/química , Sophora/química , Aminoácidos , Estrutura Molecular , Raízes de Plantas/química , Alcaloides/farmacologia
18.
Panminerva Med ; 65(1): 37-42, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32881473

RESUMO

BACKGROUND: Previous studies have shown that PRDX1 is upregulated in some types of malignant tumors. The role of PRDX1 in non-small-cancer lung carcinoma (NSCLC) remains unclear. This study aims to identify the role of PRDX1 in influencing in-vitro biological functions of NSCLC and the molecular mechanism. METHODS: We collected 50 cases of fresh NSCLC and adjacent non-tumoral tissues for detecting differential expressions of PRDX1 by quantitative real-time polymerase chain reaction (qRT-PCR). Survival time of NSCLC patients, defined as the period from the operation to the latest follow-up or death due to recurrence or metastasis, was recorded for assessing the relationship between PRDX1 and prognosis in NSCLC. Using lentivirus transfection, PRDX1 level was downregulated in NSCLC cells. Subsequently, proliferative and apoptotic abilities, and expression levels of vital genes in the Wnt/ß-Catenin signaling were examined. Finally, the significance of activated Wnt/ß-Catenin signaling during PRDX1-regulated NSCLC proliferation was explored. RESULTS: Using GEPIA database and NSCLC tissues we collected, PRDX1 was detected to be upregulated in NSCLC samples than controls. PRDX1 level was related to tumor staging and prognosis in NSCLC. Knockdown of PRDX1 attenuated proliferative ability and stimulated apoptosis in NSCLC. Protein levels of Wnt5A was downregulated in H1299 and SPC-A1 cells with PRDX1 knockdown. Overexpression of ß-Catenin enhanced proliferative ability and inhibited apoptosis in NSCLC cells with PRDX1 knockdown. CONCLUSIONS: PRDX1 is upregulated in NSCLC samples, and linked to tumor staging and prognosis. It stimulates NSCLC to proliferate by activating the Wnt/ß-Catenin signaling.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , beta Catenina/genética , beta Catenina/metabolismo , Linhagem Celular Tumoral , Via de Sinalização Wnt , Proliferação de Células , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Peroxirredoxinas/genética , Peroxirredoxinas/metabolismo
19.
J Basic Microbiol ; 63(1): 104-115, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36470591

RESUMO

The endophytic fungus Neurospora dictyophora 3ZF-02 with a special aroma was isolated from the arils of Torreya grandis. Analysis of volatile organic compounds was done by gas chromatography-mass spectrometry. A total of 46 compounds were identified in the volatile organic compounds by 3ZF-02. In the growth phase, esters, acids, along with some alcohols and ketones were the main components. During the recession period, a large amount of benzene and naphthalene compounds appeared, accompanied by the production of amines. Oleic acid, methyl abietate, terpinen-4-ol were also found. They were the same ingredients in essential oil of Torreya. The antioxidant activity and antifungal activity of all extracts were also evaluated. When cultured for 10 days, it exhibited the most significant antioxidant activity with IC50 of 1.44 and 0.95 g/L against diphenyl picryl hydrazinyl and hydroxyl radicals, respectively. In addition, the extracts cultured for 10 days exhibited the most significant antifungal activity against Candida albicans with minimum inhibitory concentration 1.56 mg/ml.


Assuntos
Antifúngicos , Compostos Orgânicos Voláteis , Antifúngicos/farmacologia , Antioxidantes/farmacologia , Fungos , Compostos Orgânicos Voláteis/farmacologia , Compostos Orgânicos Voláteis/química
20.
J Asian Nat Prod Res ; 25(5): 411-421, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35880466

RESUMO

Three previously undescribed aromatic diglycosides (1, 5, and 8) and six known analogs (2-4, 6, 7, and 9) were isolated from the roots and rhizomes of Sophora tonkinensis Gagnep. Their structures were elucidated by detailed spectroscopic analysis. The absolute configuration of compound 8 was determined by comparing the experimental and TDDFT calculated ECD spectra of 8 and aglycone 8a. Furthermore, a multistep conformer filtering procedure for TDDFT calculation of flexible glycoside was proposed, which afforded high accuracy with acceptable computing cost in determining the absolute configuration of glycosides using quantum calculated ECD.


Assuntos
Glicosídeos , Sophora , Sophora/química , Rizoma/química , Raízes de Plantas/química
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