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1.
Rev Cardiovasc Med ; 25(9): 334, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39355601

RESUMEN

Background: This study aimed to investigate the effect of tolvaptan on metabolism and electrolyte homeostasis in patients with heart failure (HF). Methods: Literature databases, such as PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure, VIP, and WanFang Data, were systematically searched for relevant trials from inception to November 4, 2023. We used the fixed effect model to combine the effect sizes and used I2 to test heterogeneity. Funnel plots were plotted to assess publication bias. Results: 16 studies were eligible for further analysis. No significant differences were identified in the incidence of hyperuricemia between the tolvaptan group and the placebo group (odds ratio (OR) = 1.23, 95% confidence interval (CI) = 0.97 to 1.55, p = 0.09). Tolvaptan decreased the levels of blood uric acid compared to traditional diuretics (mean difference (MD) = -82.8, 95% CI = -96.48 to -69.13, p < 0.00001). There was no significant difference in hypernatremia (OR = 1.62, 95% CI = 0.66 to 3.96, p = 0.29) and hyperkalemia (OR = 1.17, 95% CI = 0.93 to 1.48, p = 0.18) between the tolvaptan and control groups. Conclusions: Tolvaptan reduced the level of blood uric acid compared to conventional diuretics, and could be used as a substitute for traditional diuretics for HF patients with a high risk of gout.

2.
Acc Chem Res ; 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39356824

RESUMEN

ConspectusAlkenes and alkynes are fundamental building blocks in organic synthesis due to their commercial availability, bench-stability, and easy preparation. Selective functionalization of alkenes and alkynes is a crucial step for the synthesis of value-added compounds. Precise control over these reactions allows efficient construction of complex molecules with new functionalities. In recent decades, second- and third-row precious transition metal catalysts (palladium, platinum, rhodium, ruthenium) have been pivotal in the development of metal-catalyzed synthetic methodology. These metals exhibit excellent catalytic activity and selectivity, enabling efficient synthesis of functionalized organic molecules. However, recovery and reuse of precious metals have long been a challenge in this field. In recent years, exploration of earth-abundant metal-catalyzed organic reactions has interested both academic and industrial researchers. The development of such catalytic systems offers a promising approach to overcome the limitations of precious metal catalysts. For example, manganese is the third most naturally abundant transition metal with minimal toxicity and excellent biocompatibility. It exhibits good catalytic activity in several organic reactions, including C-H bond functionalization, selective reduction, and radical reactions. This Account outlines our recent progress in dinuclear manganese catalysis for selective functionalization of alkenes and alkynes. We have established the elementary manganese(I)-catalysis in transmetalation with R-B(OH)2. This finding has enabled us to apply the catalyst for the selective 1,2-difunctionalization of structurally diverse alkenes and alkynes. Mechanistic studies suggest a double manganese center synergistic activation model, as superior to Mn(CO)5Br in some cases. In addition, we have developed a ligand-tuned metalloradical strategy of dinuclear manganese catalysts (Mn2(CO)10), bridging the gap between the organometallics and radical chemistry, highlighting the unique radical functionalization of alkenes. Interestingly, using the same starting materials, different ligands can deliver completely different products. Meanwhile, a cooperative catalysis strategy involving manganese and other catalysts (e.g., cobalt, iminium) has also been developed and is briefly discussed. For manganese/iminium synergistic catalysis, a new mechanism for migratory insertion and demetalization-isomerization in synergistic HOMO-LUMO activation was disclosed. This strategy expands the application of low-valent manganese catalysts for enantioselective C-C bond-forming reactions. New reaction discovery is outpacing mechanism studies for dinuclear manganese catalysis, and future studies with time-resolved spectroscopy will improve understanding of the mechanism. Based on these intriguing findings, the precise functionalization of alkenes and alkynes by dinuclear manganese catalysts will expedite a novel activation model to enable late-stage functionalization of complex molecules.

3.
Redox Biol ; 77: 103383, 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39366068

RESUMEN

Homocystinuria (HCU) due to cystathionine beta-synthase (CBS) deficiency is characterized by elevated plasma and tissue homocysteine levels. There is no cure, but HCU is typically managed by methionine/protein restriction and vitamin B6 supplementation. Enzyme replacement therapy (ERT) based on human CBS has been developed and has shown significant efficacy correcting HCU phenotype in several mouse models by bringing plasma total homocysteine below the clinically relevant 100 µM threshold. As the reactive nature of homocysteine promotes disulfide formation and protein binding, and ERT is unable to normalize plasma total homocysteine levels, the mechanism of action of ERT in HCU remains to be further characterized. Here we showed that only a reduced homocysteine serves as a substrate for CBS and its availability restricts the homocysteine-degrading capacity of CBS. We also demonstrated that cells export homocysteine in its reduced form, which is efficiently metabolized by CBS in the culture medium. Availability of serine, a CBS co-substrate, was not a limiting factor in our cell-based model. Biological reductants, such as N-acetylcysteine, MESNA or cysteamine, increased the availability of the reduced homocysteine and thus promoted its subsequent CBS-based elimination. In a transgenic I278T mouse model of HCU, administration of biological reductants significantly increased the proportion of protein-unbound homocysteine in plasma, which improved the efficacy of the co-administered CBS-based ERT, as evidenced by significantly lower plasma total homocysteine levels. These results clarify the mechanism of action of CBS-based ERT and unveil novel pharmacological approaches to further increase its efficacy.

4.
Artículo en Inglés | MEDLINE | ID: mdl-39363395

RESUMEN

INTRODUCTION: Arrhythmia occurs as a common heart vascular disease. Functional food is a rich source of natural compounds with significant pharmacological, The aim of this paper is to explore its effect on arrhythmia. METHODS: By reviewing the literature and summarising the findings, we described the role of functional foods in the alleviation of cardiac arrhythmias from different perspectives. RESULTS: Our study shows that functional foods have anti-arrhythmic effects through modulation of ion channels, oxidative stress, and Calmodulin-dependent protein kinase II. CONCLUSIONS: We summarize the mechanism of arrhythmia inhibition by the active ingredients of medicinal diets in this review article, intending to provide research ideas for dietary therapy to regulate arrhythmia.

5.
Cancer Immunol Immunother ; 73(12): 240, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39358463

RESUMEN

BACKGROUND: Lenvatinib, programmed cell death 1 (PD-1) antibodies, and gemcitabine and oxaliplatin (GEMOX) chemotherapy have shown significant antitumor activity as first-line therapy against biliary tract cancer. This study evaluated their efficacy and safety as non-first-line therapy in advanced gallbladder cancer (GBC). METHODS: Patients with advanced GBC who received lenvatinib combined with anti-PD-1 antibodies and GEMOX chemotherapy as a non-first-line therapy were retrospectively analyzed. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoints were objective response rate (ORR) and safety. RESULTS: A total of 36 patients with advanced GBC were included in this study. The median follow-up time was 11.53 (95% confidence interval (CI): 2.2-20.9) months, and the ORR was 36.1%. The median OS and PFS were 15.1 (95% CI: 3.2-26.9) and 6.1 (95% CI: 4.9-7.2) months, respectively. The disease control rate (DCR) and clinical benefit rate (CBR) were 75% and 61.1%, respectively. Subgroup analysis demonstrated that patients with programmed cell death-ligand 1 (PD-L1) expression had significantly longer PFS and OS than those without PD-L1 expression. Additionally, patients with a neutrophil-lymphocyte ratio (NLR) < 5.57 had a longer OS than those with an NLR ≥ 5.57. All patients experienced adverse events (AEs), with 61.1% experiencing grade 3 or 4 AEs, including myelosuppression (13.9%) and fatigue (13.3%), alanine transaminase or aspartate transaminase levels (8.3%), and diarrhea (8.3%). No grade 5 AEs were reported. CONCLUSION: Anti-PD-1 antibodies combined with lenvatinib and GEMOX chemotherapy are effective and well-tolerated as a non-first-line therapy in advanced GBC. PD-L1 expression and baseline NLR may potentially predict treatment efficacy.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina , Neoplasias de la Vesícula Biliar , Compuestos de Fenilurea , Receptor de Muerte Celular Programada 1 , Quinolinas , Humanos , Femenino , Masculino , Neoplasias de la Vesícula Biliar/tratamiento farmacológico , Neoplasias de la Vesícula Biliar/mortalidad , Persona de Mediana Edad , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/efectos adversos , Compuestos de Fenilurea/administración & dosificación , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Estudios Retrospectivos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Adulto , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Desoxicitidina/administración & dosificación , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/administración & dosificación , Gemcitabina , Anciano de 80 o más Años , Compuestos Organoplatinos
6.
Cancer Immunol Immunother ; 73(12): 249, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39358645

RESUMEN

BACKGROUND: Treatment options for advanced intrahepatic cholangiocarcinoma (ICC) are currently limited. Chemo-containing regimens are the mainstay treatments but associated with notable toxicity, poor tolerance, and reduced compliance, necessitating exploration of alternative therapies. Lenvatinib plus PD-1 inhibitors has shown substantial clinical activity in preliminary studies. This study aimed to assess the effectiveness and safety of lenvatinib plus toripalimab (a novel PD-1 antibody) as chemo-free therapy in advanced ICC. METHODS: This retrospective study included consecutive advanced ICC patients receiving lenvatinib plus toripalimab between February 2019 and December 2023. The main outcomes were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety. Prognostic factors and exploratory analyses for genetic alternations were also conducted. RESULTS: A total of 78 patients were included, with a median follow-up of 25.9 months. Median OS and PFS were 11.3 (95% CI: 9.5-13.1) and 5.4 (95% CI: 3.8-7.0) months, respectively. ORR was 19.2% and DCR was 75.6%. The incidence of grade 3 or 4 adverse events (AEs) was 50.0%, with no grade 5 AEs reported. Patients with normal baseline CA19-9 levels exhibited a higher ORR (p = 0.011), longer PFS (11.5 versus 4.6 months; HR 0.47; p=0.005), and OS (21.0 versus 9.7 months; HR 0.43; p=0.003). The presence of IDH1 mutations correlated with increased ORR (60.0% versus 8.9%, p=0.016). CONCLUSION: Lenvatinib plus toripalimab represents an effective and well-tolerated chemo-free therapeutic option for advanced ICC. Baseline CA19-9 levels and IDH1 mutations may serve as predictive treatment-related biomarkers.


Asunto(s)
Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias de los Conductos Biliares , Biomarcadores de Tumor , Colangiocarcinoma , Compuestos de Fenilurea , Quinolinas , Humanos , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/genética , Colangiocarcinoma/mortalidad , Masculino , Femenino , Quinolinas/uso terapéutico , Quinolinas/administración & dosificación , Quinolinas/efectos adversos , Persona de Mediana Edad , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/efectos adversos , Compuestos de Fenilurea/administración & dosificación , Anciano , Estudios Retrospectivos , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de los Conductos Biliares/tratamiento farmacológico , Neoplasias de los Conductos Biliares/mortalidad , Neoplasias de los Conductos Biliares/genética , Adulto , Pronóstico , Anciano de 80 o más Años
7.
Small ; : e2407564, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39350443

RESUMEN

NiFe layered double hydroxides (LDHs) are state-of-the-art catalysts for the oxygen evolution reaction (OER) in alkaline media, yet they still face significant overpotentials. Here, quantitative boron (B) doping is introduced in NiFe LDHs (ranging from 0% to 20.3%) to effectively tailor the Ni-Fe-B electronic interactions for enhanced OER performance. The co-hydrolysis synthesis approach synchronizes the hydrolysis rates of Ni and Fe precursors with the formation rate of B─O─M (M: Ni, Fe) bonds, ensuring precise B doping into the NiFe LDHs. It is demonstrated that B, as an electron-deficient element, acts as an "electron sink" at doping levels from 0% to 13.5%, facilitating the transition of Ni2+ to the active Ni3+δ, thereby accelerating OER kinetics. However, excessive B doping (13.5-20.3%) effectively generates oxygen vacancies in the LDHs, which increases electron density at Ni2+ sites and hinders their transition to Ni3+δ, thereby reducing OER activity. Optimal OER performance is achieved at a B doping level of 13.5%, with an overpotential of only 208 mV to reach a current density of 500 mA cm-2, placing it among the most effective OER catalysts to date. This Ni-Fe-B electronic engineering opens new avenues for developing highly efficient anode catalysts for water-splitting hydrogen production.

8.
Nat Sci Sleep ; 16: 1533-1544, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39372894

RESUMEN

Objective: The aim of this study was to analyze the relationship between the characteristics of the intestinal microbiota and cytokine levels in individuals with different degrees of obstructive sleep apnea-hypopnea syndrome (OSAHS) as well as to investigate intestinal microbiota imbalances in patients with OSAHS and the associated mechanisms. Methods: Based on their sleep apnea hypopnea index (AHI), a total of 37 adults were assigned to a control group, a mild OSAHS group, or a moderate-to-severe OSAHS group. Fecal samples were collected to characterize the intestinal microbiota using metagenomic next-generation sequencing (mNGS), while blood samples were collected to detect levels of interleukin-17a (IL-17a), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6) in each group. Results: 1. There was no significant difference in the Shannon index among the three groups (P > 0.05). The three groups showed significant difference in the relative abundance of Faecalibacterium prausnitzii and Bifidobacterium adolescentis (with F values of 3.955 and 7.24, respectively, P < 0.05), while showed no significant difference in the relative abundance of B. pseudocatenulatum, Bifidobacterium longum, Klebsiella pneumoniae, and Haemophilus parainfluenzae (P > 0.05). 2. The three groups showed significant difference in the expression of serum IL-17A and TNF-α levels (with F values of 18.119 and 10.691, respectively, P < 0.05), while showed no significant difference in the expression of IL-10, IL-6, and CRP levels (P > 0.05). 3. Multiple linear regression analysis revealed that the relative abundance of F. prausnitzii was correlated with changes in BMI and AHI (with ß values of 2.585 and -0.157, respectively, P < 0.05), while the relative abundance of B. adolescentis was correlated with changes in IL-17a (with ß value of -0.161, P < 0.05). Conclusion: The study revealed a significant correlation between intestinal microbiota abundance and cytokine levels, suggesting that gut microbiota disruption in OSAHS patients may be linked to systemic chronic inflammation.

9.
Artículo en Inglés | MEDLINE | ID: mdl-39388320

RESUMEN

Surface electromyography (sEMG) is a widely employed bio-signal that captures human muscle activity via electrodes placed on the skin. Several studies have proposed methods to remove sEMG contaminants, as non-invasive measurements render sEMG susceptible to various contaminants. However, these approaches often rely on heuristic-based optimization and are sensitive to the contaminant type. A more potent, robust, and generalized sEMG denoising approach should be developed for various healthcare and human-computer interaction applications. This paper proposes a novel neural network (NN)-based sEMG denoising method called TrustEMG-Net. It leverages the potent nonlinear mapping capability and data-driven nature of NNs. TrustEMG-Net adopts a denoising autoencoder structure by combining U-Net with a Transformer encoder using a representation-masking approach. The proposed approach is evaluated using the Ninapro sEMG database with five common contamination types and signal-to-noise ratio (SNR) conditions. Compared with existing sEMG denoising methods, TrustEMG-Net achieves exceptional performance across the five evaluation metrics, exhibiting a minimum improvement of 20%. Its superiority is consistent under various conditions, including SNRs ranging from -14 to 2 dB and five contaminant types. An ablation study further proves that the design of TrustEMG-Net contributes to its optimality, providing high-quality sEMG and serving as an effective, robust, and generalized denoising solution for sEMG applications.

10.
Nano Lett ; 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39388536

RESUMEN

Long-wavelength afterglow emitters are crucial for optoelectronics and information security; however, it remains a challenge in achieving high luminescence efficiency due to the lack of effective modulation in electronic coupling and nonradiative transitions of singlet/triplet excitons. Here, we demonstrate an organic-carbon-dot (CD) hybrid system that operates via a space-confined energy transfer strategy to obtain bright afterglow emission centered at 600 nm with near-unity luminescence efficiency. Photophysical characterization and theoretical calculation confirm efficient luminescence can be assigned to the synergistic effect of intermolecular energy transfer from triplet excitons of CDs to singlets of subluminophores and the intense restraint in nonradiative decay losses of singlet/triplet-state excitons via rationally space-confined rigidification and amination modification. By utilizing precursor engineering, yellow and near-infrared afterglow centered at 575 and 680 nm with luminescence efficiencies of 94.4% and 45.9% has been obtained. Lastly, these highly emissive powders enable superior performance in lighting and information security.

11.
PLoS One ; 19(10): e0311824, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39383141

RESUMEN

The exploration of novel natural products for Parkinson's disease (PD) is a focus of current research, as there are no definitive drugs to cure or stop the disease. Campsis grandiflora (Thunb.) K. Schum (Lingxiaohua) is a traditional Chinese medicine (TCM), and the exact active constituents and putative mechanisms for treating PD are unknown. Through data mining and network pharmacology, apigenin (APi) was identified as the main active ingredient of Lingxiaohua, and key targets (TNF, AKT1, INS, TP53, CASP3, JUN, BCL2, MMP9, FOS, and HIF1A) of Lingxiaohua for the treatment of PD were discovered. The primary routes implicated were identified as PI3K/AKT, Apoptosis, TNF, and NF-κB pathways. Subsequently, therapeutic potential of APi in PD and its underlying mechanism were experimentally evaluated. APi suppressed the release of mediators of inflammation and initiation of NF-κB pathways in MES23.5 cells induced by MPP+. APi suppressed caspase-3 activity and apoptosis and elevated p-AKT levels in MES23.5 cells. Pretreatment with LY294002, a PI3K inhibitor, resulted in APi treatment blocking the activation of NF-κB pathway and expression of inflammatory factors in MES23.5 cells by activating the PI3K/AKT pathway. In conclusion, APi protects dopaminergic neurons by controlling the PI3K/AKT/NF-κB pathway, giving novel insights into the pharmacological mechanism of Lingxiaohua in treating PD.


Asunto(s)
Apigenina , FN-kappa B , Farmacología en Red , Enfermedad de Parkinson , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Apigenina/farmacología , FN-kappa B/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Enfermedad de Parkinson/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Transducción de Señal/efectos de los fármacos , Animales , Flores/química , Ratones , Humanos , Apoptosis/efectos de los fármacos , Línea Celular
12.
Nano Lett ; 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39374070

RESUMEN

The composition and physiochemical properties of the solid electrolyte interphase (SEI) significantly impact the electrochemical cyclability of the Li metal. Here, we introduce a trace dual-salt electrolyte additive (TDEA) that accelerates LiF production from FEC decomposition and improves the LiF distribution, resulting in earlier LiF precipitation and the formation of a LiF-rich SEI on the Li anode. TDEA at a millimolar-level concentration was found to alter the morphology of deposited Li, suppress Li dendrite formation, and increase the cycling time and operating current density for Li anodes. Li∥NCM811 full cells using TDEA-based electrolytes exhibited approximately two times longer lifespan than those without additives. Additionally, the TDEA-based electrolytes enabled a high energy density of 347 Wh kg-1 for 500-mAh pouch cells, maintaining stable cycling over 180 cycles under stringent conditions (N/P = 1.26 and E/C = 2.2 g A h-1). Our findings suggest that the proposed TDEA strategy offers a promising path to achieving high-performance Li metal batteries.

13.
PeerJ ; 12: e18278, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39391824

RESUMEN

The chlorophyll content (CC) directly affects photosynthesis, growth, and yield. However, the genetic basis of CC is still unclear in maize (Zea mays L.). Here, we conducted a genome-wide association study using mixed linear model for CC of the fifth leaves at seedling stage (CCFSS) and the ear leaves at filling stage (CCEFS) for 334 maize inbred lines. The heritability estimates for CCFSS and CCEFS, obtained via variance components analysis using the lme4 package in R, were 70.84% and 78.99%, respectively, indicating that the CC of leaves is primarily controlled by genetic factors. A total of 15 CC-related SNPs and 177 candidate genes were identified with a p-value < 4.49 × 10-5, which explained 4.98-7.59% of the phenotypic variation. Lines with more favorable gene variants showed higher CC. Meanwhile, Gene Ontology (GO) analysis implied that these candidate genes were probably related to chlorophyll biosynthesis. In addition, gene-based association analyses revealed that six variants in GRMZM2G037152, GRMZM5G816561, GRMZM2G324462, and GRMZM2G064657 genes were significantly (p-value < 0.01) correlated with CC, of which GRMZM2G064657 (encodes a phosphate transporter protein) and GRMZM5G816561 (encodes a cytochrome P450 protein) were specifically highly expressed in leaves tissues. Interestingly, these candidate genes were previously reported to involve in the regulation of the contents of chlorophyll in plants or Chlamydomonas. These results may contribute to the understanding of genetic basis and molecular mechanisms of maize CC and the selection of maize varieties with improved CC.


Asunto(s)
Clorofila , Estudio de Asociación del Genoma Completo , Hojas de la Planta , Polimorfismo de Nucleótido Simple , Zea mays , Zea mays/genética , Zea mays/metabolismo , Clorofila/metabolismo , Clorofila/genética , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Polimorfismo de Nucleótido Simple/genética , Genes de Plantas/genética , Fenotipo
14.
Pharmacol Res ; : 107453, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39393437

RESUMEN

Vasculogenic mimicry (VM) contributes factor to the poor prognosis of malignant melanoma. Developing deoxyhypusine synthase (DHPS) inhibitors against melanoma VM is clinically essential. In this study, we optimized and synthesized a series of compounds based on the candidate structure, and the hit compound 7k was identified through enzyme assay and cell viability inhibition screening. Both inside and outside the cell, 7k's ability to target DHPS and its high affinity were demonstrated. Molecular dynamics and point mutation indicated that mutations of K329 or V129 in DHPS abolish 7k's inhibitory activity. Using PCR arrays, solid-state antibody microarrays, and angiogenesis assays investigated 7k's impact on melanoma cells to reveal that DHPS regulates melanoma VM by promoting FGFR2 and c-KIT expression. Surprisingly, 7k was discovered to inhibit MC1R-mediated melanin synthesis in the zebrafish. Pharmacokinetic evaluations demonstrated 7k's favorable properties, and xenograft models evidenced its notable anti-melanoma efficacy, achieving a TGI of 73%. These results highlighted DHPS as key in melanoma VM formation and confirmed 7k's potential as a novel anti-melanoma agent.

15.
BMC Cancer ; 24(1): 1248, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39385125

RESUMEN

BACKGROUND: Locally advanced rectal cancer (LARC) poses unique challenges in treatment, with current neoadjuvant chemoradiotherapy (NA-CRT) showing limitations. The CapeOX regimen emerges as a potential less aggressive neoadjuvant chemotherapy (NAC) for LARC. METHODS: We conducted a retrospective study involving treatment-naïve patients with LARC from March 2014 to March 2021 who received 2-4 cycles of CapeOX NAC followed by radical surgery. Treatment response was evaluated using tumor regression grade (TRG), MRI-based TRG (MRI-TRG), and Neoadjuvant Rectal (NAR) score. RESULTS: 94.7% of patients experienced symptom improvement and 96.4% achieved sphincter-preserving surgery. Post-NAC showed significant tumor regression and MRI confirmed a tumor length reduction (P < 0.001). Clinical and pathological staging discrepancies post-NAC suggest broader therapeutic advantages. 5-year overall and disease-free survival rates were 78.4% and 73.4%. NAR scores provided better prognostic accuracy than MRI-TRG. CONCLUSION: CapeOX NAC presents notable benefits for LARC patients and its clinical significance may be underestimated. The NAR score demonstrates superior prognostic value over MRI-TRG.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Neoplasias del Recto/tratamiento farmacológico , Neoplasias del Recto/diagnóstico por imagen , Neoplasias del Recto/mortalidad , Terapia Neoadyuvante/métodos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Capecitabina/administración & dosificación , Capecitabina/uso terapéutico , Adulto , Imagen por Resonancia Magnética , Resultado del Tratamiento , Estadificación de Neoplasias , Oxaliplatino/uso terapéutico , Oxaliplatino/administración & dosificación , Pronóstico
16.
Technol Cancer Res Treat ; 23: 15330338241271935, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39376170

RESUMEN

Gastric cancer (GC) is a prevalent malignant tumor and ranks as the second leading cause of death among cancer patients worldwide. Due to its hidden nature and difficulty in detection, GC has a high incidence and poor prognosis. Traditional treatment methods such as systemic chemotherapy, radiotherapy, and surgical resection are commonly used, but they often fail to achieve satisfactory curative effects, resulting in a very low 5-year survival rate for GC patients. Currently, targeted therapy and immunotherapy are prominent areas of research both domestically and internationally. These methods hold promise for the treatment of GC. This article focuses on the signaling pathways associated with the development of GC, as well as the recent advancements and applications of targeted therapy and immunotherapy. The aim is to provide fresh insights for the clinical treatment of GC.


Asunto(s)
Inmunoterapia , Terapia Molecular Dirigida , Transducción de Señal , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/terapia , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patología , Inmunoterapia/métodos , Biomarcadores de Tumor/metabolismo , Animales , Manejo de la Enfermedad
17.
BMC Biol ; 22(1): 203, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39256728

RESUMEN

BACKGROUND: Mutations occurring in nucleic acids or proteins may affect the binding affinities of protein-nucleic acid interactions. Although many efforts have been devoted to the impact of protein mutations, few computational studies have addressed the effect of nucleic acid mutations and explored whether the identical methodology could be applied to the prediction of binding affinity changes caused by these two mutation types. RESULTS: Here, we developed a generalized algorithm named PNBACE for both DNA and protein mutations. We first demonstrated that DNA mutations could induce varying degrees of changes in binding affinity from multiple perspectives. We then designed a group of energy-based topological features based on different energy networks, which were combined with our previous partition-based energy features to construct individual prediction models through feature selections. Furthermore, we created an ensemble model by integrating the outputs of individual models using a differential evolution algorithm. In addition to predicting the impact of single-point mutations, PNBACE could predict the influence of multiple-point mutations and identify mutations significantly reducing binding affinities. Extensive comparisons indicated that PNBACE largely performed better than existing methods on both regression and classification tasks. CONCLUSIONS: PNBACE is an effective method for estimating the binding affinity changes of protein-nucleic acid complexes induced by DNA or protein mutations, therefore improving our understanding of the interactions between proteins and DNA/RNA.


Asunto(s)
Algoritmos , ADN , Mutación , Unión Proteica , ADN/metabolismo , Biología Computacional/métodos , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética
18.
Bioresour Technol ; 412: 131410, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39226940

RESUMEN

Temperature is the critical factor affecting the efficiency and cost of anaerobic digestion (AD). The current work develops a shift-temperature AD (STAD) between 35 °C and 55 °C, intending to optimise microbial community and promote substrate conversion. The experimental results showed that severe inhibition of biogas production occurred when the temperature was firstly increased stepwise from 35 °C to 50 °C, whereas no inhibition was observed at the second warming cycle. When the organic load rate was increased to 6.37 g VS/L/d, the biogas yield of the STAD reached about 400 mL/g VS, nearly double that of the constant-temperature AD (CTAD). STAD promoted the proliferation of Methanosarcina (up to 57.32 %), while severely suppressed hydrogenophilic methanogens. However, when the temperature was shifted to 35 °C, most suppressed species recovered quickly and the excess propionic acid was quickly consumed. Metagenomic analysis showed that STAD also promoted gene enrichment related to pathways metabolism, membrane functions, and methyl-based methanogenesis.


Asunto(s)
Biocombustibles , Temperatura , Anaerobiosis , Biocombustibles/microbiología , Reactores Biológicos/microbiología , Metano/metabolismo , Methanosarcina/metabolismo , Microbiota/fisiología
19.
Am J Trop Med Hyg ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39255787

RESUMEN

Tuberculous arthritis of the elbow joint (TAEJ) is a relatively rare infectious bone and joint disease. Misdiagnosed owing to inconspicuous early symptoms, often the elbow joint has suffered serious damage at the time of treatment. This study retrospectively investigated the clinical manifestations, population characteristics, clinical diagnosis, surgical treatment, and functional recovery of elbow joint tuberculosis (TB). A retrospective study of 40 patients was conducted. These patients were diagnosed with tuberculous arthritis of the elbow from June 2007 to August 2021 and were diagnosed with TAEJ by fine-needle aspiration biopsy or biopsy of surgically excised lesions. All patients underwent surgery after taking regular anti-TB drugs and chemotherapy for 2 weeks. Visual analogue scale score, Mayo elbow performance score, and hospital for special surgery assessment scale score were used to evaluate postoperative functional recovery. Imaging tests were used to evaluate patients' postoperative recovery. Forty patients were followed up for an average of 12.5 ±0.5 months. Erythrocyte sedimentation rate and C-reactive protein values returned to normal after anti-TB drug chemotherapy combined with surgical removal of infected lesion tissue; only one patient relapsed 16 months after surgery. Tuberculous arthritis of the elbow joint should be diagnosed in an early stage based on clinical manifestations, laboratory tests, and histopathological examinations. Complete surgical removal of the lesions should be performed after chemotherapy with anti-TB drugs for 2 weeks. The corresponding operation should be selected according to the damage in the elbow joint.

20.
Heliyon ; 10(16): e36221, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39253119

RESUMEN

Urban-rural development is an important driving force for regional economic growth. The existing researches have studied this issue from various perspectives, but they ignore the impact of big data on the economy. In the post pandemic era, big data, as an emerging production factor, has a significant indicative effect in promoting urban-rural economic recovery and fostering new business forms. Therefore, fully considering the factor of big data can help reveal its impact mechanism on urban-rural economic growth in the post-epidemic period. Based on the data of 30 provinces and cities in China, this paper introduced big data on the basis of traditional models and constructed a multi-dimensional factor indicator system. At the same time, the panel regression model was established by using unit root test, Hausman test and precision test. Through benchmark regression and heterogeneity analysis, the impact of urban-rural development factors on economic growth was discussed. The results showed that the panel model passed all tests, and its regression error was stable below 5 %. Transportation, technology, and the three major industries can all promote positive economic growth, with a significance of 1 %. The three industries' contribution to economic growth ranks the third, second and first industries in order. In addition, the good ecological environment contributes to the benign economic growth during the study period. A 1 % increase in forest cover would drive economic growth by 0.215 %. But the impact of public's attention on the overall economy was an indirect effect manifested through its physical industries.The regional heterogeneity indicated that each element had different effects on economic development in eastern, central and western regions. Based on its results, this paper proposed suggestions for each region. In addition, this study found that the Internet attention reflected by big data did not directly drive economic growth, but affected economic growth through indirect channels such as information flow and resource allocation of real industries. This study provided data support for the existing theoretical review, and provided policy reference for the rational planning and industrial layout of China's regional economy.

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