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1.
World J Gastrointest Oncol ; 16(9): 3932-3954, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-39350988

RESUMEN

BACKGROUND: Cancer is one of the most serious threats to human health worldwide. Conventional treatments such as surgery and chemotherapy are associated with some drawbacks. In recent years, traditional Chinese medicine treatment has been increasingly advocated by patients and attracted attention from clinicians, and has become an indispensable part of the comprehensive treatment for gastric cancer. AIM: To investigate the mechanism of Xiaojianzhong decoction (XJZ) in the treatment of gastric cancer (GC) by utilizing network pharmacology and experimental validation, so as to provide a theoretical basis for later experimental research. METHODS: We analyzed the mechanism and targets of XJZ in the treatment of GC through network pharmacology and bioinformatics. Subsequently, we verified the impact of XJZ treatment on the proliferative ability of GC cells through CCK-8, apoptosis, cell cycle, and clone formation assays. Additionally, we performed Western blot analysis and real-time quantitative PCR to assess the protein and mRNA expression of the core proteins. RESULTS: XJZ mainly regulates IL6, PTGS2, CCL2, MMP9, MMP2, HMOX1, and other target genes and pathways in cancer to treat GC. The inhibition of cell viability, the increase of apoptosis, the blockage of the cell cycle at the G0/G1 phase, and the inhibition of the ability of cell clone formation were observed in AGS and HGC-27 cells after XJZ treatment. In addition, XJZ induced a decrease in the mRNA expression of IL6, PTGS2, MMP9, MMP2, and CCL2, and an increase in the mRNA expression of HOMX1. XJZ significantly inhibited the expression of IL6, PTGS2, MMP9, MMP2, and CCL2 proteins and promoted the expression of the heme oxygenase-1 protein. CONCLUSION: XJZ exerts therapeutic effects against GC through multiple components, multiple targets, and multiple pathways. Our findings provide a new idea and scientific basis for further research on the molecular mechanisms underlying the therapeutic effects of XJZ in the treatment of GC.

2.
Chembiochem ; : e202400593, 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39387673

RESUMEN

Sulfide:quinone oxidoreductase (Sqr) catalyzes the initial procedure on sulfide transformation, alongside sulfide (H2S, S2-) oxidization coupled with coenzyme Q (CoQ) reducing and reactive sulfur species (RSS) production. Here, we assessed the reactivity of propanethiol (PT) as an alternative substrate for Sqr to maintain intracellular homeostasis in strain S-1 capable of degrading emerging sulfur-containing pollutants. We deleted a gene encoding Sqr, and serial transcriptional difference induced by RSS dynamics was therefore revealed. Next, the reaction properties of two Sqr homologs from strains JMP134 and S-1 were comparatively characterized, respectively. As a result, an additional role of Sqr in yielding RSS from PT was found in reaction mixture prepared by cell-free extracts or purified enzymes. Interestingly, the transformation velocity of PT by Sqr was slower than that of sulfides. From this scenario, it was a rate-determining step that PT as a nucleophilic compound can be added into Sqr cysteine to form disulfide bond and likely serve nonoptimal sulfur recipient. In addition, the role of persulfidation driven by RSS in combating oxidative and sulfur stresses required to be further clarified. Nevertheless, this promiscuity of Sqr-binding organosulfur compounds and its catalytic modulation underscored that expanded substrates might benefit sulfide homeostasis in thiol-degrading bacteria.

3.
Chemosphere ; 366: 143458, 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39366491

RESUMEN

Reuse of municipal-treated wastewater for agricultural irrigation is becoming increasingly prevalent due to growing demand and decline in freshwater supplies. However, the microbial contamination profile, including antibiotic resistance genes (ARGs), virulence factors (VFs), and human bacterial pathogens (HBPs) in agricultural soil irrigated with municipal-treated wastewater for paddy cultivation, was unknown. Here, metagenomic analysis was applied to provide a systematic insight into the resistome, VFs and HBPs in paddy soils irrigated with municipal-treated wastewater. The obtained results revealed that the residual antibiotics in municipal-treated wastewater has an impact on the antibiotic resistome by increasing both the total number and abundance of ARGs. Furthermore, it was found that sul1 could serve as a potential risk indicator for assessing ARG contamination. VFs, core HBP abundance, and dangerous pathogens remain unaffected by municipal-treated wastewater irrigation for paddy. The good coexistence patterns of ARGs-HBPs and ARGs-VFs demonstrated the presence of resistant pathogenic bacteria. The network analysis revealed that ARGs-bearing Legionella pneumophila, Mycobacterium marinum, Bordetella pertussis, Staphylococcus aureus, and Pseudomonas aeruginosa might be ranked as high-risk HBPs. Additionally, our investigation also demonstrated that reuse of municipal-treated wastewater for agricultural irrigation had no detrimental effects on rice plant growth and grain quality. This study was the first to investigate the response of VFs and HBPs in paddy soil under long-term municipal-treated wastewater irrigation. The obtained results provide a scientific basis for the safe application of municipal-treated wastewater.

4.
Front Pharmacol ; 15: 1435923, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39469624

RESUMEN

Background: Fluoroquinolones are broad-spectrum antibiotics with significant antimicrobial activity. Despite their therapeutic benefits, they are associated with a range of adverse drug reactions (ADRs), particularly those affecting the central nervous system (CNS). This study aimed to analyze the psychiatric ADRs linked to fluoroquinolones using data from the FDA Adverse Event Reporting System (FAERS) database. Methods: A retrospective pharmacovigilance study was conducted using FAERS data from Q1 2004 to Q4 2023. The data processing phase involved the FDA-recommended deduplication method, and ADRs were classified according to Medical Dictionary for Regulatory Activities (MedDRA). Disproportionality analysis was performed using the reporting odds ratio (ROR), and statistical significance was assessed using the Chi-square test or Fisher's exact test. Results: The study identified 84,777 reports associated with fluoroquinolones, with 359,480 Preferred Terms-annotated entries, 27,816 of these reports were psychiatric ADRs. Mood disorders were the most frequently reported, including anxiety, depression, and delirium, with some reports escalating to suicidal ideation and behaviors. The Standardized MedDRA Query classification system was used to categorize these ADRs into Depression, Suicide/self-injury, Psychosis and psychotic disorders, and Non-infectious encephalopathy/delirium. Ciprofloxacin was most frequently linked to depression and suicidal ideation, while moxifloxacin showed a robust correlation with delirium. The risk of psychiatric ADRs varied by age group, with affective disorders more prevalent in adults under 65 and psychosis and delirium in those over 65. Conclusion: Fluoroquinolones are associated with a range of psychiatric ADRs, with notable differences between the drugs in the class. The study highlights the need for caution in prescribing fluoroquinolones, particularly for patients with pre-existing mental health conditions or those in higher risk age groups. The findings also underscore the importance of considering age-specific preventive strategies when administering these antibiotics.

5.
Heliyon ; 10(19): e38732, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39430460

RESUMEN

Background: Triple-negative breast cancer is a breast cancer subtype characterized by its challenging prognosis, and establishing prognostic models aids its clinical treatment. PANoptosis, a recently identified type of programmed cell death, influences tumor growth and patient outcomes. Nonetheless, the precise impact of PANoptosis-related genes on the prognosis of triple-negative breast cancer has yet to be determined. Methods: Clinical information for the triple-negative breast cancer samples was collected from the Gene Expression Omnibus and The Cancer Genome Atlas databases, while 19 PANoptosis-related genes were sourced from previous studies. We first categorized PANoptosis-related subtypes and determined the differentially expressed genes between them. Subsequently, we developed and validated a PANoptosis-associated predictive model using LASSO and Cox multivariate regression analyses. Statistical evaluations were conducted using R software, and the mRNA expression levels of the genes were quantified using real-time PCR. Results: Using consensus clustering analysis, we divided triple-negative breast cancer patients into two clusters based on PANoptosis-related genes and identified 1054 differentially expressed genes between these clusters. Prognostic-related genes were subsequently selected to re-cluster patients, validating their predictive ability. A prognostic model was then constructed based on four genes: BTN2A2, CACNA1H, PIGR, and S100B. The expression and enriched cell types of these genes were examined and the expression levels were validated in vitro. Furthermore, the model was validated, and a nomogram was created to enhance personalized risk assessment. The risk score, proven to be an independent prognostic indicator for triple-negative breast cancer, showed a positive correlation with both age and disease stage. Immune infiltration and drug sensitivity analyses suggested appropriate therapies for different risk groups. Mutation profiles and pathway enrichment were analyzed, providing insights into potential therapeutic targets. Conclusion: A PANoptosis-related prognostic model was successfully developed for triple-negative breast cancer, offering a novel approach for predicting patient prognosis and guiding treatment strategies.

6.
Langmuir ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39255345

RESUMEN

Biomass and its derivatives, with their renewable characteristics, cost-effectiveness, and controllable structural and compositional properties, are promising precursors for carbon materials. Herein, N,O-codoped carbon aerogels were synthesized by carbonization and zinc nitrate activation of histidine. The specific surface area (SSA) was markedly increased with the addition of zinc nitrate, and the maximum value achieved 853 m2 g-1 for ZHC-11 obtained with the molar ratio of 1:1 between histidine and zinc nitrate. The D/G-band intensity ratio increased from 1.55 for the histidine-derived control sample HC to 1.65 for ZHC-11, indicating the enhancement of amorphous feature. The nitrogen content increased from 6.5% for HC to 1.60 for ZHC-11. The optimized microstructure and enriched heteroatom doping are beneficial to the capacitance performance. The optimum electrode exhibited 234.1 F g-1 at 0.1 A g-1 and maintained 116.5 F g-1 at 60 A g-1 in a three-electrode system. In particular, the symmetric supercapacitor showed 121.9 F g-1 and 19.5 Wh kg-1 at 0.2 A g-1. This research offers guidance on the cost-effective synthesis of carbon materials for supercapacitors, while also providing novel insights to realize the complete utilization of biomass derivatives.

7.
Front Microbiol ; 15: 1471305, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39296284

RESUMEN

Citrus diseases caused by fungal pathogens drastically decreased the yield and quality of citrus fruits, leading to huge economic losses. Given the threats of chemical pesticides on the environment and human health, biocontrol agents have received considerable attention worldwide as ecofriendly and sustainable alternative to chemical fungicides. In the present study, we isolated a Bacillus velezensis strain TZ01 with potent antagonistic effect against three citrus pathogenic fungi: Diaporthe citri, Colletotrichum gloeosporioides and Alternaria alternata. The culture supernatant of this strain exhibited remarkable antifungal activity on potato dextrose agar plates and detached leaves of five citrus varieties. Treatment with TZ01 culture supernatant obviously affected the hyphal morphology and caused nucleic acid leakage. The crude lipopeptides (LPs) extracted from the culture supernatant were found as the major active ingredients, and could maintain the activity under a wide range of temperature and pH and ultraviolet radiation. Furthermore, the type of LPs, produced in vitro, were explored. Whole-genome sequencing of TZ01 revealed secondary metabolite gene clusters encoding synthetases for non-ribosomal peptides and polyketide production, and gene clusters responsible for the synthesis of three important LPs (surfactin, iturin, and fengycin) were identified in the genome. The liquid chromatography-mass spectrometry analysis confirmed the presence of various homologs of surfactin A, bacillomycin D, and fengycin A in the extracted LPs. Taken together, these results contribute to the possible biocontrol mechanisms of B. velezensis strain TZ01, as well as providing a promising new candidate strain as a biological control agent for controlling citrus fungal pathogens.

8.
Microorganisms ; 12(9)2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39338492

RESUMEN

Burkholderia is the second largest source of natural product bacteria after Actinomyces and can produce many secondary metabolites including pyrrolnitrin (PRN). Natural products of microbial origin are usually found in trace amounts, so in metabolic engineering, promoter engineering is often used to regulate gene expression to increase yield. In this study, an endogenous strong promoter was identified based on RNA-seq to overexpress biosynthetic genes to increase the production of PRN. By analyzing the transcriptomic data of the antagonistic bacterium Burkholderia sp. JP2-270 in three different development periods, we screened 50 endogenous promoters with high transcriptional activity, nine of which were verified by an obvious fluorescent signal via fluorescence observation. Then, combined with RT-qPCR analysis, Php, the promoter of a hypothetical protein, was found to be significantly expressed in all three periods. In order to increase the suitability of endogenous promoters, the promoter Php was shortened at different lengths, and the results show that a sequence length of 173 bp was necessary for its activity. Moreover, this promoter was used to overexpress the PRN biosynthesis genes (prnA, prnB, prnC and prnD) in JP2-270, resulting in a successful increase in gene expression levels by 40-80 times. Only the overexpression of the prnB gene successfully increased PRN production to 1.46 times that of the wild type. Overall, the endogenous strong promoters screened in this study can improve gene expression and increase the production of secondary metabolites in JP2-270 and other strains.

9.
Electrophoresis ; 45(19-20): 1796-1804, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39091179

RESUMEN

Various dyes are used to visualize DNA bands in agarose gel electrophoresis (AGE) by the methods of pre- or post-staining. The DNA dye user's guides generally state that the binding of the dye to DNA will affect DNA mobility in electrophoresis, thus recommending post-staining for accurate measurement of DNA size. However, many AGE performers prefer pre-staining procedures for reasons such as convenience, real-time observation of DNA bands, and/or the use of a minimal amount of dye. The detrimental effect of the dye on DNA mobility and the associated risk for inaccurate measurement of DNA size are often overlooked by AGE performers. Here we quantitatively determine the impact on DNA migration imposed by frequently used dyes, including GelRed, ethidium bromide (EB), and Gold View. It was observed that pre-staining with GelRed and EB significantly slowed down DNA migration to cause as much as 39.1% overestimation on the size of sample DNA, whereas Gold View had little effect. The slowdown of DNA migration increased with dye concentration until it plateaued when the dye concentration reached a saturated level. Thus, to take advantage of pre-staining, saturated levels of DNA dyes should always be applied for both DNA samples and DNA markers to ensure a fair comparison of DNA sizes. In addition, GelRed and EB display much higher sensitivity than Gold View in the detection of DNA bands in post-staining. The saturated concentrations, cost considerations, and other useful features of these frequently used dyes are summarized for the information of AGE performers.


Asunto(s)
Colorantes , ADN , Electroforesis en Gel de Agar , Etidio , Electroforesis en Gel de Agar/métodos , ADN/análisis , ADN/química , Colorantes/química , Colorantes/análisis , Etidio/química
10.
Molecules ; 29(16)2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39202998

RESUMEN

Tumor-associated macrophages (TAMs) are pivotal in the tumor microenvironment (TME) of hepatocellular carcinoma (HCC), influencing various stages from initiation to metastasis. Understanding the role of TAMs in HCC is crucial for developing novel therapeutic strategies. Macrophages exhibit plasticity, resulting in M1 and M2 phenotypes, with M1 macrophages displaying antitumor properties and M2 macrophages promoting tumor progression. Targeting TAMs to alter their polarization could offer new avenues for HCC treatment. ß,ß-dimethylacrylalkannin (DMAKN), a natural naphthoquinone, has gained attention for its antitumor properties. However, its impact on TAMs modulation remains unclear. This study investigates DMAKN's modulation of TAMs and its anti-HCC activity. Using an in vitro model with THP-1 cells, we induced M1 macrophages with LPS/IFN-γ and M2 macrophages with IL-4/IL-13, confirming polarization with specific markers. Co-culturing these macrophages with HCC cells showed that M1 cells inhibited HCC growth, while M2 cells promoted it. Screening for non-toxic DMAKN concentrations revealed its ability to induce M1 polarization and enhance LPS/IFN-γ-induced M1 macrophages, both showing anti-HCC effects. Conversely, DMAKN suppressed IL-4/IL-13-induced M2 polarization, inhibiting M2 macrophages' promotion of HCC cell viability. In summary, DMAKN induces and enhances M1 polarization while inhibiting M2 polarization of macrophages, thereby inhibiting HCC cell growth. These findings suggest that DMAKN has the potential to regulate TAMs in HCC, offering promise for future therapeutic development.


Asunto(s)
Carcinoma Hepatocelular , Proliferación Celular , Neoplasias Hepáticas , Naftoquinonas , Macrófagos Asociados a Tumores , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Naftoquinonas/farmacología , Naftoquinonas/química , Macrófagos Asociados a Tumores/efectos de los fármacos , Macrófagos Asociados a Tumores/metabolismo , Proliferación Celular/efectos de los fármacos , Microambiente Tumoral/efectos de los fármacos , Línea Celular Tumoral , Células THP-1 , Antineoplásicos/farmacología , Antineoplásicos/química
11.
Materials (Basel) ; 17(15)2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39124303

RESUMEN

For damage tolerance design in engineering components, the fracture toughness value, KIC, of the material is essential. However, obtaining specimens of sufficient thickness from stir friction welded plates is challenging, and often, the experimental test values do not meet the necessary criteria, preventing the experimental fracture toughness, Kq, from being recognized as plane strain fracture toughness KIC. The fracture toughness Kq of 2195 Al-Li alloy welding seams with different thicknesses was measured on the forward and backward sides. Microstructure characterization was conducted by scanning electron microscope (SEM). The results indicated minimal significant differences in grain size between the advancing and retreating sides of the weld nugget zone. In specimens of the same thickness, fracture toughness measurements along the normal direction of the joint cross-section showed a high similarity between the advancing and retreating sides of the weld nugget zone. Utilizing the quantitative relationships between fracture toughness and sample thickness derived from both the fracture K and G criteria, it is possible to predict the fracture toughness of thick plates using thin plates. This study employs these relationships to calculate the fracture toughness KIC of 2195 aluminum-lithium alloy friction stir welds. The KIC values obtained are 41.65 MPa·m1/2 from the fracture K criterion and 43.54 MPa·m1/2 from the fracture G criterion.

12.
Sci Total Environ ; 951: 175739, 2024 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-39182773

RESUMEN

Regional climatic differences increase the complexity of tree radial growth responses to climate change in the monsoon marginal zones and may alter the carbon sequestration capacity of forests. In this study, we collected cores of Pinus tabulaeformis trees at nine sampling sites across different regions. We analysed the relationship between tree-ring width chronology and climatic factors at different sites using dendroecological methods. We used the tree-ring index to calculate resistance, recovery, and resilience as well as to explore the capacity of radial growth to cope with drought events. The results indicate that (1) Drought was the primary factor limiting tree growth, and tree-ring climate response patterns varied across three regions. Tree growth was sensitive to both temperature and precipitation in the eastern Qilian Mountains, while it was more sensitive to temperature in the Hassan Mountains and more sensitive to precipitation in the Helan Mountains. (2) The tree-ring climate response pattern remained unstable over time, and the relative influence of current climate on tree growth increased. (3) The ecological resilience of trees to extreme events varies across three regions, which could be attributed to regional moisture conditions and the duration of drought. In the context of the management and protection of trees in the study area in the future, more attention should be paid to the elasticity of tree growth after drought events.


Asunto(s)
Cambio Climático , Sequías , Pinus , Pinus/crecimiento & desarrollo , Pinus/fisiología , China , Bosques , Clima , Temperatura , Árboles/crecimiento & desarrollo
13.
Mikrochim Acta ; 191(9): 529, 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39123066

RESUMEN

A ratiometric fluorescence probe based on carbon quantum dots with 420 nm emission (bCQDs) and a p-phenylenediamine-derived fluorescence probe with 550 nm emission (yprobe) is constructed for the detection of Mn2+. The presence of Mn2+ results in the enhanced absorption band at 400 nm of yprobe, and the fluorescence of yprobe is significantly enhanced based on the chelation-enhanced fluorescence mechanism. The fluorescence of bCQDs is then quenched based on the inner filtration effect. The ratio (I550/I420) linearly increases with the increase of Mn2+ concentration within 2.00 × 10-7-1.50 × 10-6 M, and the limit of detection is 1.76 × 10-9 M. Given the fluorescence color changing from blue to yellow, the visual sensing of Mn2+ is feasible based on bCQDs/yprobe coupled with RGB value analysis. The practicability of the proposed method has been verified in tap water, lake water, and sparkling water beverage, indicating that bCQDs/yprobe has promising application in Mn2+ monitoring.

14.
Int J Biol Macromol ; 277(Pt 4): 134404, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39111460

RESUMEN

Atopic dermatitis (AD) is a prevalent chronic skin condition characterized by complex immune responses. Chamomile possesses potent anti-inflammatory properties and has been widely used in treating various skin diseases. This study aimed to assess the therapeutic benefits of chamomile volatile oil nanoemulsion gels (CVO-NEGs) for the treatment of AD. Chamomile volatile oil nanoemulsions (CVO-NEs) were prepared using the phase transition method, yielding spherical nanoparticles with a particle size of 19.07 nm. Subsequently, Bletilla striata polysaccharides were employed to encapsulate CVO-NEs, resulting in the formation of CVO-NEGs. In vivo studies demonstrated that the preparation of CVO-NEGs enhanced the biological activity of volatile oil in AD therapy. Histopathological results indicated that CVO-NEGs reduced skin damage, epidermal thickness, and mast cell infiltration. CVO-NEGs suppressed IgG production and reduced the levels of cytokines, including TNF-α, IL-4, and IFN-γ, in AD mice. Furthermore, flow cytometry revealed that CVO-NEGs were involved in regulating the differentiation of CD4+ T cell subsets. The immune imbalance of Th1/Th2 in AD mice can be controlled, resulting in a reduction in the hypersensitivity reaction caused by excessive Th2 activation. In conclusion, the present study confirms that CVO-NEGs have the potential to serve as an effective alternative treatment for AD.


Asunto(s)
Manzanilla , Citocinas , Dermatitis Atópica , Emulsiones , Aceites Volátiles , Polisacáridos , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/patología , Animales , Aceites Volátiles/farmacología , Aceites Volátiles/química , Polisacáridos/farmacología , Polisacáridos/química , Emulsiones/química , Ratones , Manzanilla/química , Citocinas/metabolismo , Geles/química , Nanopartículas/química , Piel/efectos de los fármacos , Piel/patología , Femenino , Ratones Endogámicos BALB C , Modelos Animales de Enfermedad
15.
Bioorg Chem ; 151: 107670, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39096560

RESUMEN

Pseudolaric Acid B (PAB), a natural product with remarkable anti-tumor activity, is a starting point for new anticancer therapeutics. We designed and synthesized 27 PAB derivatives and evaluated their anti-proliferative activities against four cancer cell lines: MCF-7, HCT-116, HepG2, and A549. Compared with unmodified PAB, the PAB derivatives showed stronger anti-proliferative activity. The ability of compound D3 (IC50 = 0.21 µM) to inhibit HCT-116 cells was approximately 5.3 times that of PAB (IC50 = 1.11 µM) and the antiproliferative action was unrelated to cytotoxicity (SI=20.38), indicating its superior safety profile (PAB; SI=0.95). Compound D3 effectively suppressed the EdU-positive rate and reduced colony formation, arrested HCT-116 cells in the S and G2/M phases and induced apoptosis. In vivo experiments further demonstrated low toxicity of compound D3 while suppressing tumor growth in mice. In summary, given its strong anti-proliferative effect and relative safety, further development of compound D3 is warranted.


Asunto(s)
Antineoplásicos , Apoptosis , Proliferación Celular , Diterpenos , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Animales , Relación Estructura-Actividad , Ratones , Apoptosis/efectos de los fármacos , Estructura Molecular , Diterpenos/farmacología , Diterpenos/química , Diterpenos/síntesis química , Relación Dosis-Respuesta a Droga , Línea Celular Tumoral , Ratones Endogámicos BALB C , Ratones Desnudos
16.
Phytomedicine ; 134: 155959, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39178682

RESUMEN

BACKGROUND: ß,ß-Dimethylacrylalkannin (DMAKN), a natural naphthoquinone found in Zicao, a traditional Chinese medicine (TCM), serves as the designated quantitative marker in the Chinese Pharmacopoeia. Despite its established role in assessing Zicao quality, DMAKN's biological potential remains underexplored in research. METHODS: We investigated DMAKN's involvement in Zicao's anti-hepatocellular carcinoma (HCC) properties using a combination of HPLC content analysis and comprehensive bioinformatics. Subsequently, both in vitro and in vivo experiments were conducted to evaluate DMAKN's efficacy against HCC. Mechanistic investigations focused on elucidating DMAKN's impact on cell cycle regulation and induction of cell death. RESULTS: Integrated HPLC analysis and bioinformatics identified DMAKN as the primary active compound responsible for Zicao's anti-HCC activity. In vitro and in vivo studies confirmed DMAKN's potent efficacy against HCC. Notably, DMAKN demonstrated dual effects on HCC cells: inhibiting proliferation at lower doses and inducing rapid cell death at higher doses. Mechanistic insights revealed that low-dose DMAKN induced G2/M phase cell cycle arrest through modulation of CDK1 and Cdc25C phosphorylation, while high-dose DMAKN triggered necrosis. Importantly, high-dose DMAKN caused a sharp increase in intracellular ROS levels in a short time, while low-dose DMAKN gradually increased ROS levels over a long period. Additionally, low-dose DMAKN-induced ROS activated the JNK pathway, crucial for cell cycle arrest, whereas high-dose DMAKN-induced necrosis was ROS-dependent but JNK-independent. CONCLUSION: This study underscores DMAKN's pivotal role as the principal anti-HCC compound in Zicao, delineating its differential effects and underlying mechanisms. These results demonstrate the potential of DMAKN as a therapeutic agent for the treatment of HCC, providing important information for further study and advancement in cancer therapy.


Asunto(s)
Carcinoma Hepatocelular , Puntos de Control del Ciclo Celular , Neoplasias Hepáticas , Necrosis , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/tratamiento farmacológico , Humanos , Animales , Puntos de Control del Ciclo Celular/efectos de los fármacos , Necrosis/tratamiento farmacológico , Naftoquinonas/farmacología , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Línea Celular Tumoral , Antineoplásicos Fitogénicos/farmacología , Ratones Desnudos , Ratones , Ratones Endogámicos BALB C , Especies Reactivas de Oxígeno/metabolismo , Proliferación Celular/efectos de los fármacos , Masculino , Células Hep G2 , Fosfatasas cdc25/metabolismo , Apoptosis/efectos de los fármacos , Proteína Quinasa CDC2
17.
Phys Med Biol ; 69(15)2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-38981592

RESUMEN

Objective. Positron Emission Tomography and Magnetic Resonance Imaging (PET-MRI) systems can obtain functional and anatomical scans. But PET suffers from a low signal-to-noise ratio, while MRI are time-consuming. To address time-consuming, an effective strategy involves reducing k-space data collection, albeit at the cost of lowering image quality. This study aims to leverage the inherent complementarity within PET-MRI data to enhance the image quality of PET-MRI.Approach. A novel PET-MRI joint reconstruction model, termed MC-Diffusion, is proposed in the Bayesian framework. The joint reconstruction problem is transformed into a joint regularization problem, where data fidelity terms of PET and MRI are expressed independently. The regular term, the derivative of the logarithm of the joint probability distribution of PET and MRI, employs a joint score-based diffusion model for learning. The diffusion model involves the forward diffusion process and the reverse diffusion process. The forward diffusion process adds noise to transform a complex joint data distribution into a known joint prior distribution for PET and MRI simultaneously, resembling a denoiser. The reverse diffusion process removes noise using a denoiser to revert the joint prior distribution to the original joint data distribution, effectively utilizing joint probability distribution to describe the correlations of PET and MRI for improved quality of joint reconstruction.Main results. Qualitative and quantitative improvements are observed with the MC-Diffusion model. Comparative analysis against LPLS and Joint ISAT-net on the ADNI dataset demonstrates superior performance by exploiting complementary information between PET and MRI. The MC-Diffusion model effectively enhances the quality of PET and MRI images.Significance. This study employs the MC-Diffusion model to enhance the quality of PET-MRI images by integrating the fundamental principles of PET and MRI modalities and leveraging their inherent complementarity. Furthermore, utilizing the diffusion model to learn the joint probability distribution of PET and MRI, thereby elucidating their latent correlation, facilitates a more profound comprehension of the priors obtained through deep learning, contrasting with black-box prior or artificially constructed structural similarities.


Asunto(s)
Procesamiento de Imagen Asistido por Computador , Imagen por Resonancia Magnética , Tomografía de Emisión de Positrones , Procesamiento de Imagen Asistido por Computador/métodos , Humanos , Difusión , Imagen Multimodal , Relación Señal-Ruido , Teorema de Bayes , Encéfalo/diagnóstico por imagen
18.
Plant Phenomics ; 6: 0197, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39049839

RESUMEN

Due to nutrient stress, which is an important constraint to the development of the global agricultural sector, it is now vital to timely evaluate plant health. Remote sensing technology, especially hyperspectral imaging technology, has evolved from spectral response modes to pattern recognition and vegetation monitoring. This study established a hyperspectral library of 14 NPK (nitrogen, phosphorus, potassium) nutrient stress conditions in rice. The terrestrial hyperspectral camera (SPECIM-IQ) collected 420 rice stress images and extracted as well as analyzed representative spectral reflectance curves under 14 stress modes. The canopy spectral profile characteristics, vegetation index, and principal component analysis demonstrated the differences in rice under different nutrient stresses. A transformer-based deep learning network SHCFTT (SuperPCA-HybridSN-CBAM-Feature tokenization transformer) was established for identifying nutrient stress patterns from hyperspectral images while being compared with classic support vector machines, 1D-CNN (1D-Convolutional Neural Network), and 3D-CNN. The total accuracy of the SHCFTT model under different modeling strategies and different years ranged from 93.92% to 100%, indicating the positive effect of the proposed method on improving the accuracy of identifying nutrient stress in rice.

19.
J Infect Dev Ctries ; 18(7): 1118-1123, 2024 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-39078798

RESUMEN

INTRODUCTION: Coxsackievirus A10 (CVA10) is a non-enveloped, positive-sense single-stranded RNA virus classified within the Enterovirus genus in the Picornaviridae family. It is among the pathogens that can cause hand, foot and mouth disease. This study aimed to analyze the temporal and spatial distribution of CVA10 in China to understand its epidemiological characteristics of CVA10. METHODOLOGY: We collected the VP1 sequences of CVA10 from January 1, 2004, to December 31, 2019, from the GenBank database and created the global map using MapChart. We selected 56 known CVA10 genotype sequences. Then, MEGA6.06 was used to construct a phylogenetic tree with the collected gene sequences and the known reference sequences for comparative analysis to assess the distribution of CVA10 genotypes in different countries between 2004 and 2019. RESULTS: CVA10 has been widely detected or reported globally. In China, the prevalent genotype of CVA10 was mainly genotype B before 2008 and genotype C after 2009. In other countries, the prevalence of genotype D was dominant, followed by genotypes C and F, and the prevalence of CVA10 varied from continent to continent. CONCLUSIONS: Monitoring CVA10 genotypes or evolutionary branches should be strengthened, and the study of epidemic genotype characteristics should be enhanced. This will serve as a basis for further research and development of monovalent CVA10 or polyvalent vaccines designed for effective disease prevention.


Asunto(s)
Genotipo , Filogenia , China/epidemiología , Humanos , Enfermedad de Boca, Mano y Pie/virología , Enfermedad de Boca, Mano y Pie/epidemiología , Proteínas de la Cápside/genética , Enterovirus/genética , Enterovirus/clasificación , Enterovirus/aislamiento & purificación , Prevalencia
20.
Am J Cancer Res ; 14(5): 2037-2054, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38859843

RESUMEN

Glioblastoma is the most common cancer in the brain, resistant to conventional therapy and prone to recurrence. Therefore, it is crucial to explore novel therapeutics strategies for the treatment and prognosis of GBM. In this study, through analyzing online datasets, we elucidated the expression and prognostic value of POLR2J and its co-expressed genes in GBM patients. Functional experiments, including assays for cell apoptosis and cell migration, were used to explore the effects of POLR2J and vorinostat on the proliferation and migration of GBM cells. The highest overexpression of POLR2J, among all cancer types, was observed in GBM. Furthermore, high expression of POLR2J or its co-expressed genes predicted a poor outcome in GBM patients. DNA replication pathways were significantly enriched in the GBM clinical samples with high POLR2J expression, and POLR2J suppression inhibited proliferation and triggered cell cycle G1/S phase arrest in GBM cells. Moreover, POLR2J silencing activated the unfolded protein response (UPR) and significantly enhanced the anti-GBM activity of vorinostat by suppressing cell proliferation and inducing apoptosis. Additionally, POLR2J could interact with STAT3 to promote the metastatic potential of GBM cells. Our study identifies POLR2J as a novel oncogene in GBM progression and provides a promising strategy for the chemotherapeutic treatment of GBM.

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