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1.
J Biomater Appl ; : 8853282241284106, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39255374

RESUMEN

γ-Cyclodextrin-based metal-organic frameworks (γ-CD-MOF) were successfully synthesized using the solvent diffusion method and applied as carriers for trans-N-p-coumaroyltyramine (N-p-t-CT, NCT) to study the solubability, stability, sustained release and inhibitory activity against α-glucosidase. The solubilization effect of γ-CD-MOF on N-p-t-CT was performed using impregnation (NCT@CD-MOF-1) and co-crystallization (NCT@CD-MOF-2) methods. X-ray diffraction, scanning electron microscope (SEM), fourier transform infrared spectrometer (FTIR), and N2 adsorption/desorption were used to characterize the MOFs before and after loading NCT. The results showed that NCT@CD-MOF-2 had a better solubability for N-p-t-CT, 145.03 µg/mg of drug loading capacity could be achieved, and the solubility of NCT@CD-MOF-2 in water was 366 times higher than free N-p-t-CT. In addition, the stabilities of N-p-t-CT under temperature, UV light and pH conditions were greatly improved after encapsulation in γ-CD-MOF. Furthermore, NCT@CD-MOFs had a sustained release of N-p-t-CT over an extended period in vitro due to the primary encapsulation in pore structures. Notably, γ-CD-MOF loaded with N-p-t-CT showed superior inhibitory activity against α-glucosidase compared to free N-p-t-CT. Cytotoxicity studies demonstrated that NCT@CD-MOF-2 had low toxicity in vitro and perfect biocompatibility with HL-7702 cells, and γ-CD-MOF could reduce the toxicity of free N-p-t-CT at higher concentrations.

2.
Colloids Surf B Biointerfaces ; 245: 114200, 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39236360

RESUMEN

A water stable cyclodextrin MOF (Cu-SD) was synthesized with γ-cyclodextrin derivative as organic ligand and Cu2+ as metal center to co-crystallizely load glycyrrhizic acid (GL) and glycyrrhetinic acid (GA). Cu-SD has a high drug loading capacity for GL (499.91 µg/mg) and GA (112.37 µg/mg), and the drug-loaded materials had a controlled release in different meadiums. In addition, Cu-SD and its drug loaded materials demonstrated better inhibiting α-glucosidase activity than the control drug acarbose. Furthermore, Cu-SD presented excellent antibacterial activity, and the antibacterial activity was significantly enhanced after GA and GL being encapsulated by Cu-SD. Moreover, both free and drug-loaded materials had good anti-inflammatory activities, and the anti-inflammatory effects of GL@Cu-SD and GA@Cu-SD were superior to those of their corresponding free drugs. Cu-SD, GL@Cu-SD and GA@Cu-SD demonstrated good biocompatibility and were applied to treat the wounds of diabetic rats. The experimental results showed that GL@Cu-SD and GA@Cu-SD had good promoting effects on the recovery of chronic diabetic wounds by suppressing wound inflammation.

3.
EMBO Rep ; 25(9): 3970-3989, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39090319

RESUMEN

The tandem Tudor-like domain-containing protein Spindlin1 (SPIN1) is a transcriptional coactivator with critical functions in embryonic development and emerging roles in cancer. However, the involvement of SPIN1 in DNA damage repair has remained unclear. Our study shows that SPIN1 is recruited to DNA lesions through its N-terminal disordered region that binds to Poly-ADP-ribose (PAR), and facilitates homologous recombination (HR)-mediated DNA damage repair. SPIN1 promotes H3K9me3 accumulation at DNA damage sites and enhances the interaction between H3K9me3 and Tip60, thereby promoting the activation of ATM and HR repair. We also show that SPIN1 increases chemoresistance. These findings reveal a novel role for SPIN1 in the activation of H3K9me3-dependent DNA repair pathways, and suggest that SPIN1 may contribute to cancer chemoresistance by modulating the efficiency of double-strand break (DSB) repair.


Asunto(s)
Proteínas de Ciclo Celular , Resistencia a Antineoplásicos , Histonas , Lisina Acetiltransferasa 5 , Fosfoproteínas , Unión Proteica , Humanos , Resistencia a Antineoplásicos/genética , Histonas/metabolismo , Lisina Acetiltransferasa 5/metabolismo , Lisina Acetiltransferasa 5/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Fosfoproteínas/metabolismo , Fosfoproteínas/genética , Roturas del ADN de Doble Cadena , Reparación del ADN por Recombinación , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Proteínas de la Ataxia Telangiectasia Mutada/genética , Poli Adenosina Difosfato Ribosa/metabolismo , Línea Celular Tumoral , Daño del ADN , Reparación del ADN , Proteínas Asociadas a Microtúbulos
4.
Ying Yong Sheng Tai Xue Bao ; 35(4): 897-908, 2024 Apr 18.
Artículo en Chino | MEDLINE | ID: mdl-38884224

RESUMEN

Understanding water absorption mechanisms of sand-fixing plants is important for the rational establishment of plant community structures, thereby providing a scientific basis for desertification control and the efficient utilization of water resources in sandy areas. Based on the hydrogen and oxygen isotopic compositions of precipi-tation, soil water, xylem water, and groundwater, coupled with soil water-heat dynamics, annual water consumption characteristics of vegetation, using the multi-source linear mixing model (IsoSource), we analyzed the differences in water sources between Salix psammophila and Artemisia ordosica, during winter and the growing season. We further examined the effects of groundwater depth (2 m and 10 m), soil freezing-thawing, and drought on their water utilization to elucidate water absorption mechanisms of those species. The results showed that: 1) During soil freezing-thawing period (January to March), S. psammophila mainly utilized soil water in 60-120 cm depths below the frozen layer (69.1%). In the green-up season (April and May), soil water from the 0-60 cm layers could satisfy the water demand of S. psammophila (30.9%-87.6%). During the dry period of the growing season (June), it predominantly utilized soil water at the depth of 120-160 cm (27.4%-40.8%). Over the rainy season (July and September), soil water in 0-60 cm depths provided 59.8%-67.9% of the total water required. A. ordosica, with shallow roots, could not utilize soil water after complete freezing of root zone but could overwinter by storing water in rhizomes during autumn. During the growing season, it primarily relied on 0-40 cm soil layer (23.4%-86.8%). During the dry period, it mainly utilized soil water from 40-80 cm and 80-160 cm soil layers, with utilization rates of 14.6%-74.4% and 21.8%-78.2%, respectively. 2) With decreasing groundwater depth, vegetation shifted its water absorption depth upward, with water source of S. psammophila transitioning from 120-160 cm to 60-160 cm layers, while A. ordosica shifted water absorption depth from 80-160 cm to 0-40 cm. S. psammophila's utilization of soil water is influenced by transpiration, adopting an "on-demand" approach to achieve a balance between water supply and energy conservation, whereas A. ordosica tends to utilize shallow soil water, exhibiting a higher depen-dence on water sources from a single soil layer.


Asunto(s)
Artemisia , Salix , Arena , Suelo , Agua , Agua/análisis , Agua/metabolismo , Artemisia/crecimiento & desarrollo , Artemisia/metabolismo , China , Suelo/química , Salix/crecimiento & desarrollo , Salix/metabolismo , Clima Desértico , Agua Subterránea/química , Agua Subterránea/análisis , Ecosistema
5.
Foods ; 13(10)2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38790726

RESUMEN

Yams are the edible subterranean rhizomes, or tubers, of plants from the genus Dioscorea. There are approximately 600 species of yam plants in the world, with more than 90 of these growing in East Asia. One particular species, Dioscorea opposita Thunb., is highly praised as "the Chinese yam". This distinction arises from millennia of storied history, both as a nutritional food source and as a principal ingredient in traditional Chinese medicine. Among the many cultivars of Dioscorea opposita Thunb., Huai Shanyao has been widely regarded as the best. This review surveyed the historical background, physiochemical composition, applications as food and medicine, and research prospects for the Chinese yam. Modern science is finally beginning to confirm the remarkable health benefits of this yam plant, long-known to the Chinese people. Chinese yam promises anti-diabetic, anti-oxidative, anti-inflammatory, immunomodulatory, anti-hyperlipidemic, anti-hypertensive, anti-cancer, and combination treatment applications, both as a functional food and as medicine.

6.
J Biochem Mol Toxicol ; 38(4): e23684, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38533528

RESUMEN

Lung cancer is the leading cause of cancer-related deaths worldwide. Circular RNA (circRNA) circ_0088036 is a recently discovered circRNA known for its roles in rheumatoid arthritis. The study aimed to study the function of circ_0088036 in lung adenocarcinoma (LUAD). Circ_0088036 expressions were analyzed in the Gene Expression Omnibus (GEO) database. The relationship between circ_0088036 expressions and clinicopathological data of LUAD was assessed. The messenger RNA and protein levels were analyzed by quantitative real-time polymerase chain reaction and Western blot. Cell viability, apoptosis, and invasion were tested by Cell Counting Kit-8, flow cytometry, and transwell assay. The direct interaction between microRNA-203 (miR-203) and circ_0088036 or specificity protein 1 (SP1) was confirmed by dual-luciferase reporter assay, RNA pull-down, and RNA immunoprecipitation assays. Circ_0088036 was overexpressed in LUAD from the analysis of the GEO database. The poor prognosis was found in the patients with high expressions of circ_0088036. The level of Circ_0088036 was increased in LUAD tissues and cells. In terms of function, the deletion of circ_0088036 inhibited LUAD tumorigenesis in vitro by repressing cell growth, invasion, and epithelial-mesenchymal transition (EMT). In mechanism, circ_0088036 could competitively sponge miR-203, thereby affecting the expressions of the target gene SP1. In addition, lessening of miR-203 and enlarging of SP1 could eliminate the anticancer effect of short hairpin RNA-circ_0088036 on LUAD cells. Besides, the knockout of circ_0088036 hindered the growth of xenografted tumors in vivo. Circ_0088036 promoted the LUAD cell growth, invasion, and EMT via modulating the miR-203/SP1 axis in LUAD.


Asunto(s)
Adenocarcinoma del Pulmón , Neoplasias Pulmonares , MicroARNs , Humanos , Línea Celular Tumoral , Proliferación Celular , ARN Circular
7.
Top Curr Chem (Cham) ; 382(1): 6, 2024 Feb 24.
Artículo en Inglés | MEDLINE | ID: mdl-38400859

RESUMEN

The kinetically inert, six coordinated, octahedral Pt(IV) complexes are termed dual-, triple-, or multi-action prodrugs based on the nature of the axially substituted ligands. These ligands are either inert or biologically active, where the nature of these axial ligands provides additional stability, synergistic biological activity or cell-targeting ability. There are many literature reports from each of these classes, mentioning the varied nature of these axial ligands. The ligands comprise drug molecules such as chlorambucil, doxorubicin, valproic acid, ethacrynic acid, biologically active chalcone, coumarin, combretastatin, non-steroidal anti-inflammatory drugs (NSAIDs) and many more, potentiating the anti-proliferative profile or reducing the side effects associated with cisplatin therapy. The targeting and non-targeting nature of these moieties exert additive or synergistic effects on the anti-cancer activity of Pt(II) moieties. Herein, we discuss the effects of these axially oriented ligands and the changes in the non-leaving am(m)ine groups and in the leaving groups on the biological activity. In this review, we have presented the latest developments in the field of Pt(IV) complexes that display promising activity with a reduced resistance profile. We have discussed the structure activity relationship (SAR) and the effects of the ligands on the biological activity of Pt(IV) complexes with cisplatin, oxaliplatin, carboplatin and the Pt core other than approved drugs. This literature work will help researchers to get an idea about Pt(IV) complexes that have been classified based on the aspects of their biological activity.


Asunto(s)
Antineoplásicos , Profármacos , Platino (Metal)/química , Cisplatino/farmacología , Antineoplásicos/farmacología , Antineoplásicos/química , Profármacos/farmacología , Profármacos/química , Profármacos/uso terapéutico , Clorambucilo
8.
J Mol Cell Biol ; 15(7)2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-37381178

RESUMEN

Mono-ADP-ribosylation (MARylation) is a post-translational modification that regulates a variety of biological processes, including DNA damage repair, cell proliferation, metabolism, and stress and immune responses. In mammals, MARylation is mainly catalyzed by ADP-ribosyltransferases (ARTs), which consist of two groups: ART cholera toxin-like (ARTCs) and ART diphtheria toxin-like (ARTDs, also known as PARPs). The human ARTC (hARTC) family is composed of four members: two active mono-ADP-ARTs (hARTC1 and hARTC5) and two enzymatically inactive enzymes (hARTC3 and hARTC4). In this study, we systematically examined the homology, expression, and localization pattern of the hARTC family, with a particular focus on hARTC1. Our results showed that hARTC3 interacted with hARTC1 and promoted the enzymatic activity of hARTC1 by stabilizing hARTC1. We also identified vesicle-associated membrane protein-associated protein B (VAPB) as a new target of hARTC1 and pinpointed Arg50 of VAPB as the ADP-ribosylation site. Furthermore, we demonstrated that knockdown of hARTC1 impaired intracellular calcium homeostasis, highlighting the functional importance of hARTC1-mediated VAPB Arg50 ADP-ribosylation in regulating calcium homeostasis. In summary, our study identified a new target of hARTC1 in the endoplasmic reticulum and suggested that ARTC1 plays a role in regulating calcium signaling.


Asunto(s)
ADP-Ribosilación , Calcio , Animales , Humanos , Calcio/metabolismo , ADP Ribosa Transferasas/genética , ADP Ribosa Transferasas/metabolismo , Procesamiento Proteico-Postraduccional , Homeostasis , Mamíferos , Proteínas de Transporte Vesicular/metabolismo
9.
Nucleic Acids Res ; 52(4): 1878-1895, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38153123

RESUMEN

The exonuclease ISG20L2 has been initially characterized for its role in the mammalian 5.8S rRNA 3' end maturation, specifically in the cleavage of ITS2 of 12S precursor ribosomal RNA (pre-rRNA). Here, we show that human ISG20L2 is also involved in 18S pre-rRNA maturation through removing the ITS1 region, and contributes to ribosomal biogenesis and cell proliferation. Furthermore, we determined the crystal structure of the ISG20L2 nuclease domain at 2.9 Å resolution. It exhibits the typical αßα fold of the DEDD 3'-5' exonuclease with a catalytic pocket located in the hollow near the center. The catalytic residues Asp183, Glu185, Asp267, His322 and Asp327 constitute the DEDDh motif in ISG20L2. The active pocket represents conformational flexibility in the absence of an RNA substrate. Using structural superposition and mutagenesis assay, we mapped RNA substrate binding residues in ISG20L2. Finally, cellular assays revealed that ISG20L2 is aberrantly up-regulated in colon adenocarcinoma and promotes colon cancer cell proliferation through regulating ribosome biogenesis. Together, these results reveal that ISG20L2 is a new enzymatic member for 18S pre-rRNA maturation, provide insights into the mechanism of ISG20L2 underlying pre-rRNA processing, and suggest that ISG20L2 is a potential therapeutic target for colon adenocarcinoma.


Asunto(s)
Adenocarcinoma , Neoplasias del Colon , Animales , Humanos , ARN Ribosómico 18S/metabolismo , Precursores del ARN/genética , Precursores del ARN/metabolismo , Adenocarcinoma/genética , Neoplasias del Colon/genética , ARN Ribosómico/genética , ARN Ribosómico/metabolismo , Ribosomas/genética , Ribosomas/metabolismo , Procesamiento Postranscripcional del ARN , Exonucleasas/genética , Exonucleasas/metabolismo , ARN Ribosómico 5.8S/genética , Mamíferos/genética
10.
Front Endocrinol (Lausanne) ; 14: 1212647, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38144566

RESUMEN

Background: Metabolic syndrome (MetS) is a group of co-occurring conditions that increase the risk of cardiovascular disease, which include the conditions of hypertension, overweight or obesity, hyperglycemia, and dyslipidemia. Psychological stress is gradually being taken seriously, stemming from the imbalance between environmental demands and individual perceptions. However, the potential causal relationship between psychological stress and MetS remains unclear. Method: We conducted cross-sectional and bidirectional Mendelian randomization (MR) analyses to clarify the potential causal relationship of psychological stress with MetS and its components. Multivariable logistic regression models were used to adjust for potential confounders in the cross-sectional study of the Chinese population, including 4,933 individuals (70.1% men; mean age, 46.13 ± 8.25). Stratified analyses of sexual characteristics were also performed. Bidirectional MR analyses were further carried out to verify causality based on summary-level genome-wide association studies in the European population, using the main analysis of the inverse variance-weighted method. Results: We found that higher psychological stress levels were cross-sectionally associated with an increased risk of hypertension in men (odds ratio (OR), 1.341; 95% confidence interval (CI), 1.023-1.758; p = 0.034); moreover, higher levels of hypertension were cross-sectionally associated with an increased risk of psychological stress in men and the total population (men: OR, 1.545 (95% CI, 1.113-2.145); p = 0.009; total population: OR, 1.327 (95% CI, 1.025-1.718); p = 0.032). Genetically predicted hypertension was causally associated with a higher risk of psychological stress in the inverse-variance weighted MR model (OR, 2.386 (95% CI, 1.209-4.710); p = 0.012). However, there was no association between psychological stress and MetS or the other three risk factors (overweight or obesity, hyperglycemia, and dyslipidemia) in cross-sectional and MR analyses. Conclusion: Although we did not observe an association between psychological stress and MetS, we found associations between psychological stress and hypertension both in cross-sectional and MR studies, which may have implications for targeting hypertension-related factors in interventions to improve mental and metabolic health. Further study is needed to confirm our findings.


Asunto(s)
Dislipidemias , Hiperglucemia , Hipertensión , Síndrome Metabólico , Masculino , Humanos , Adulto , Persona de Mediana Edad , Femenino , Síndrome Metabólico/epidemiología , Síndrome Metabólico/genética , Estudios Transversales , Sobrepeso , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Estrés Psicológico/complicaciones , Estrés Psicológico/genética , Obesidad , Hipertensión/epidemiología , Hipertensión/genética
11.
Front Microbiol ; 14: 1285922, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38143862

RESUMEN

Introduction: The impact of groundwater table depth (GTD) on bacterial communities and soil nutrition in revegetated areas remains unclear. Methods: We investigated the impacts of plant growth and soil physicochemical factors on rhizosphere bacterial communities under different GTD. Results: The four plant growth indices (Pielou, Margalef, Simpson, and Shannon-Wiener indices) and soil water content (SWC) at the Artem and Salix sites all showed a decreasing trend with increasing GTD. Salix had a higher nutrient content than Artem. The response of plant rhizosphere bacterial communities to GTD changes were as follows. Rhizosphere bacteria at the Artem and Salix sites exhibited higher relative abundance and alpha diversity in SW (GTD < 5 m) compared than in DW (GTD > 5 m). Functional microbial predictions indicated that the rhizosphere bacterial communities of Artem and Salix promoted carbon metabolism in the SW. In contrast, Artem facilitated nitrogen cycling, whereas Salix enhanced both nitrogen cycling and phototrophic metabolism in the DW. Discussion: Mantel test analysis revealed that in the SW of Artem sites, SWC primarily governed the diversity of rhizosphere and functional bacteria involved in the nitrogen cycle by affecting plant growth. In DW, functional bacteria increase soil organic carbon (SOC) to meet nutrient demands. However, higher carbon and nitrogen availability in the rhizosphere soil was observed in the SW of the Salix sites, whereas in DW, carbon nutrient availability correlated with keystone bacteria, and changes in nitrogen content could be attributed to nitrogen mineralization. This indicates that fluctuations in the groundwater table play a role in regulating microbes and the distribution of soil carbon and nitrogen nutrients in arid environments.

12.
IEEE Int Conf Rehabil Robot ; 2023: 1-5, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37941252

RESUMEN

Previously, we proposed a dynamic energy regeneration used in robotic prostheses. However, a dynamic energy regeneration cannot provide enough torque at low speeds and for a robotic prostheses, low torque may result in falling down in some cases. In this study, we proposed a plugging electrical energy regeneration instead of dynamic electrical energy regeneration, which can provide relatively larger torque at low speeds. Firstly, the mathematical model and formula of a dynamic energy regeneration and a plugging energy regeneration were given. Theoretically, for a plugging energy regeneration, due to the current drain from the power supply, the braking current is larger than the current for a dynamic energy regeneration, at the same low speed, indicating more braking torque. Further, we designed a drive circuit of energy regeneration, to verify two methods of a dynamic energy regeneration and a plugging energy regeneration. Experiment results showed that at low speeds, the braking torque is larger using a plugging energy regeneration than the torque using a dynamic energy regeneration, in accordance with the results from the mathematical model. From the mathematical model and physical experiments, this study showed the potential of a plugging energy regeneration used in a robotic prosthesis, to deal with the weak braking torque at low speeds.


Asunto(s)
Modelos Teóricos , Regeneración , Humanos , Torque , Fenómenos Biomecánicos
13.
Structure ; 31(12): 1578-1588.e3, 2023 12 07.
Artículo en Inglés | MEDLINE | ID: mdl-37794593

RESUMEN

The mammalian HORMA domain-containing protein 1 (HORMAD1) regulates DNA mismatch repair and homologous recombination (HR) repair in many cancers. Here, we show that the structure of human HORMAD1 adopts a self-closed conformation and displays an intra-molecular HORMA domain-closure motif interaction mode. Structural and biochemical data suggest that the interaction modes of the peptide motifs from HORMAD2 and MCM9 with HORMAD1 are highly similar to that of HORMAD1 own closure motif. The peptide motifs from diverse binding partners of HORMAD1 share a conserved Ser-Glu-Pro sequence. Additionally, structural comparison unveiled the HORMA-peptide motif interaction mode diversity among HORMA-containing proteins. Finally, cell-based assays revealed that this HORMA-closure motif interaction pattern contributes to DNA mismatch repair and is required for HORMAD1-dependent HR repair. Together, our results provide structural and biochemical insights into the common theme and functional plasticity of the HORMA domain-containing protein family, and also reveal a universal regulation mechanism for HORMAD1.


Asunto(s)
Proteínas de Ciclo Celular , Proteínas Nucleares , Animales , Humanos , Proteínas de Ciclo Celular/metabolismo , Proteínas Nucleares/metabolismo , Péptidos , Mamíferos/metabolismo
14.
Int J Biol Macromol ; 250: 126155, 2023 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-37549765

RESUMEN

The soluble crude polysaccharides from Dioscorea opposita (DOP1 and DOP2) were prepared and characterized. DOP1 and DOP2 obtained carbohydrate (65.71% and 70.18%, respectively), uronic acid (63.71% and 24.84%, respectively) and protein (8.09% and 9.51%, respectively) with molecular weight of 49.24 kDa and 21.62 kDa, respectively. DOP samples were mainly composed of mannose, glucose, galacturonic acid, galactose, and glucuronic acid. The digestibility in vitro, antioxidant activity and intestinal peristalsis effect were then investigated. DOP1 and DOP2 were degraded with decreased molecular weights (39.58 kDa and 18.56 kDa respectively), increased reducing sugar contents (from 16.95% to 19.27%; 12.45% to 15.50% respectively) and free monosaccharides (from 0.89% to 1.42%; 0.90% to 1.14% respectively) after gastric digestion. Both DOP1 and DOP2 were resistant to intestinal digestion, suggesting that DOP samples can be considered as a dietary fiber. Additionally, DOP1 and DOP2 exhibited antioxidant activities positively correlated with the concentration and remained the activities after gastrointestinal digestion in vitro. Furthermore, DOP reduced the fluorescence intensity significantly, indicating DOP can promote the intestinal peristalsis of zebrafish larvae (5 pdf) at 500 µg/mL. Therefore, DOP1 and DOP2 have a better functionality as dietary fibers, including antioxidant activity and intestinal peristalsis promotion, which can be developed as functional foods.


Asunto(s)
Antioxidantes , Dioscorea , Animales , Antioxidantes/farmacología , Pez Cebra/metabolismo , Dioscorea/metabolismo , Peristaltismo , Polisacáridos/farmacología , Polisacáridos/metabolismo , Fibras de la Dieta
15.
EMBO Rep ; 24(9): e56230, 2023 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-37489617

RESUMEN

Fibrillarin (FBL) is a highly conserved nucleolar methyltransferase responsible for methylation of ribosomal RNA and proteins. Here, we reveal a role for FBL in DNA damage response and its impact on cancer proliferation and sensitivity to DNA-damaging agents. FBL is highly expressed in various cancers and correlates with poor survival outcomes in cancer patients. Knockdown of FBL sensitizes tumor cells and xenografts to DNA crosslinking agents, and leads to homologous recombination-mediated DNA repair defects. We identify Y-box-binding protein-1 (YBX1) as a key interacting partner of FBL, and FBL increases the nuclear accumulation of YBX1 in response to DNA damage. We show that FBL promotes the expression of BRCA1 by increasing the binding of YBX1 to the BRCA1 promoter. Our study sheds light on the regulatory mechanism of FBL in tumorigenesis and DNA damage response, providing potential therapeutic targets to overcome chemoresistance in cancer.


Asunto(s)
Antineoplásicos , Neoplasias , Humanos , Neoplasias/metabolismo , Proteínas Cromosómicas no Histona/metabolismo , Antineoplásicos/uso terapéutico , Daño del ADN , Línea Celular Tumoral , Proteína 1 de Unión a la Caja Y/genética , Proteína 1 de Unión a la Caja Y/metabolismo , Proteína BRCA1/genética
16.
Nucleic Acids Res ; 51(14): 7649-7665, 2023 08 11.
Artículo en Inglés | MEDLINE | ID: mdl-37334830

RESUMEN

Nucleic acid ADP-ribosylation has been established as a novel modification found in a wide diversity of prokaryotic and eukaryotic organisms. tRNA 2'-phosphotransferase 1 (TRPT1/TPT1/KptA) possesses ADP-ribosyltransferase (ART) activity and is able to ADP-ribosylate nucleic acids. However, the underlying molecular mechanism remains elusive. Here, we determined crystal structures of TRPT1s in complex with NAD+ from Homo sapiens, Mus musculus and Saccharomyces cerevisiae. Our results revealed that the eukaryotic TRPT1s adopt common mechanisms for both NAD+ and nucleic acid substrate binding. The conserved SGR motif induces a significant conformational change in the donor loop upon NAD+ binding to facilitate the catalytic reaction of ART. Moreover, the nucleic acid-binding residue redundancy provides structural flexibility to accommodate different nucleic acid substrates. Mutational assays revealed that TRPT1s employ different catalytic and nucleic acid-binding residues to perform nucleic acid ADP-ribosylation and RNA 2'-phosphotransferase activities. Finally, cellular assays revealed that the mammalian TRPT1 is able to promote endocervical HeLa cell survival and proliferation. Together, our results provide structural and biochemical insights into the molecular mechanism of TRPT1 for nucleic acid ADP-ribosylation.


Asunto(s)
Fosfotransferasas (Aceptor de Grupo Alcohol) , Proteínas de Saccharomyces cerevisiae , Animales , Humanos , Ratones , Adenosina Difosfato Ribosa/metabolismo , ADP Ribosa Transferasas/genética , ADP Ribosa Transferasas/metabolismo , ADP-Ribosilación , Células HeLa , NAD/metabolismo , Ácidos Nucleicos/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/química , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética
17.
Langmuir ; 39(26): 9069-9077, 2023 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-37358076

RESUMEN

A Dioscorea opposita Thunb polysaccharide (DOP)-modified ZIF8 material was developed in this study, which can be used as a "smart" glucose-responsive carrier to control the slow release of drugs. The 3-aminophenylboronic acid (APBA) functionalized carboxylated long-chain polymer poly(ethylene glycol) (PEG) segments, which were first modified on the surface of ZIF8 nanoparticles with a hydrogen bond and then chemically cross-linked with DOP through a borate ester bond, leading to the drugs loaded on ZIF8 being "closed" in PBS but being "open" via taking off the DOP coating in high concentrations of glucose; thus, leakage can be prevented in the drug loaded and a glucose-triggered release can effectively result. Moreover, the materials showed good biocompatibility and the released trans-N-p-coumaroyltyramine (NCT) could work synergistically with the DOP to improve insulin resistance and promote glucose consumption in insulin-resistant HepG2 cells.


Asunto(s)
Dioscorea , Glucosa , Dioscorea/química , Polisacáridos/química , Insulina
18.
JMIR Public Health Surveill ; 9: e44541, 2023 04 07.
Artículo en Inglés | MEDLINE | ID: mdl-37027203

RESUMEN

BACKGROUND: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease involving multiple organs throughout the body. The health care-seeking behaviors, disease progression of SLE, and patients' knowledge of and attitudes toward SLE have not been characterized in China. OBJECTIVE: The aim of this study was to depict the health care-seeking behaviors, disease progression, and medications in patients with SLE and to examine the factors associated with their disease flares, knowledge, and attitudes toward SLE in China. METHODS: We conducted a cross-sectional survey in 27 provinces in China. Descriptive statistical methods were used to depict the demographic characteristics, health care-seeking behaviors, medications, and health status. Multivariable logistic regression models were used to identify the factors associated with disease flares, medication changes, and attitudes toward SLE. An ordinal regression model was used to examine the factors associated with the knowledge of the treatment guidelines. RESULTS: We recruited 1509 patients with SLE, and 715 had lupus nephritis (LN). Approximately 39.96% (603/1509) of the patients with SLE were primarily diagnosed with LN, and 12.4% (112/906) developed LN (mean time 5.2 years) from non-LN. Patients whose registered permanent residences or workplaces in other cities from the same province and adjacent provinces seeking health care accounted for 66.9% (569/850) and 48.8% (479/981) of the patients with SLE in the provincial capital cities, respectively. Mycophenolate mofetil was the most commonly used immunosuppressive drug in patients without LN (185/794, 23.3%) and patients with LN (307/715, 42.9%). Femoral head necrosis (71/228, 31.1%) and hypertension (99/229, 43.2%) were the most common adverse event (AE) and chronic disease during treatment, respectively. Change of hospitals for medical consultation (odds ratio [OR] 1.90, 95% CI 1.24-2.90) and development of 1 chronic disease (OR 3.60, 95% CI 2.04-6.24) and AE (OR 2.06, 95% CI 1.46-2.92) and more were associated with disease flares. A pregnancy plan (OR 1.58, 95% CI 1.18-2.13) was associated with changes in medication. Only 242 (16.03%) patients with SLE were familiar with the treatment guidelines, and patients with LN tended to be more familiar with the disease (OR 2.20, 95% CI 1.81-2.68). After receiving treatment, 891 (59.04%) patients changed their attitudes toward SLE from fear to acceptance, and patients with college education or higher (OR 2.09, 95% CI 1.10-4.04) were associated with a positive attitude toward SLE. CONCLUSIONS: A large proportion of patients seeking health care in the provincial capital cities of China migrated from other cities. Persistent monitoring of potential AEs and chronic diseases during SLE treatment and managing patients who changed hospitals for medical consultation are essential for controlling disease flares. Patients had insufficient knowledge about SLE treatment guidelines and would benefit from health education to maintain a positive attitude toward SLE.


Asunto(s)
Lupus Eritematoso Sistémico , Nefritis Lúpica , Embarazo , Femenino , Humanos , Estudios Transversales , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/epidemiología , Nefritis Lúpica/complicaciones , Nefritis Lúpica/diagnóstico , Nefritis Lúpica/tratamiento farmacológico , Progresión de la Enfermedad , Atención a la Salud
19.
Int Wound J ; 20(2): 302-312, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35801278

RESUMEN

We performed a meta-analysis to evaluate the effect of chronic obstructive pulmonary disease on surgical site wound infection, and other postoperative problems after coronary artery bypass grafting. A systematic literature search up to April 2022 was performed and 37 444 subjects with coronary artery bypass grafting at the baseline of the studies; 4320 of them were with the chronic obstructive pulmonary disease, and 33 124 were without chronic obstructive pulmonary disease. Odds ratio (OR), and mean difference (MD) with 95% confidence intervals (CIs) were calculated to assess the effect of chronic obstructive pulmonary disease on surgical site wound infection, and other postoperative problems after coronary artery bypass grafting using the dichotomous, and contentious methods with a random or fixed-effect model. The chronic obstructive pulmonary disease subjects had a significantly higher surgical site wound infection (OR, 1.27; 95% CI, 1.01-1.60, P = 0.04), respiratory failure (OR, 1.84; 95% CI, 1.55-2.18, P < 0.001), mortality (OR, 1.61; 95% CI, 1.37-1.89, P < 0.001), pneumonia (OR, 2.30; 95% CI, 1.97-2.68, P < 0.001), pleural effusion (OR, 1.78; 95% CI, 1.12-2.83, P = 0.02), stroke (OR, 1.99; 95% CI, 1.17-3.36, P = 0.01), and length of intensive care unit stay (MD, 0.73; 95% CI, 0.19-1.26, P = 0.008) after coronary artery bypass grafting compared with subjects without chronic obstructive pulmonary disease. However, chronic obstructive pulmonary disease subjects did not show any significant difference in length of hospital stay (MD, 0.83; 95% CI, -0.01 to 1.67, P = 0.05), and pneumothorax (OR, 1.59; 95% CI, 0.98-2.59, P = 0.06) after coronary artery bypass grafting compared with subjects without chronic obstructive pulmonary disease. The chronic obstructive pulmonary disease subjects had a significantly higher surgical site wound infection, respiratory failure, mortality, pneumonia, pleural effusion, stroke, and length of intensive care unit stay, and no significant difference in length of hospital stay, and pneumothorax after coronary artery bypass grafting compared with subjects without chronic obstructive pulmonary disease. The analysis of outcomes should be with caution because of the low sample size of 1 out of 11 studies in the meta-analysis and a low number of studies in certain comparisons.


Asunto(s)
Enfermedad de la Arteria Coronaria , Derrame Pleural , Neumotórax , Enfermedad Pulmonar Obstructiva Crónica , Insuficiencia Respiratoria , Accidente Cerebrovascular , Humanos , Puente de Arteria Coronaria/efectos adversos , Puente de Arteria Coronaria/métodos , Enfermedad de la Arteria Coronaria/cirugía , Derrame Pleural/complicaciones , Neumotórax/complicaciones , Complicaciones Posoperatorias/etiología , Enfermedad Pulmonar Obstructiva Crónica/cirugía , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Insuficiencia Respiratoria/complicaciones , Accidente Cerebrovascular/etiología , Infección de la Herida Quirúrgica , Resultado del Tratamiento
20.
J Enzyme Inhib Med Chem ; 37(1): 2540-2550, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36120953

RESUMEN

In this work, a highly effective separation approach mediated by 5-Lipoxygenase (5-LOX) was established for screening and isolation of anti-inflammatory ingredients from leaves of Lonicera japonica Thunb. (LLJT). Using 5-LOX immobilised on TiO2 nanotubes as a microreactor, the targeted screening was exploited by combining with HPLC-MS system. Four compounds confirmed as luteolin, luteoside, lonicerin, and isochlorogenic acid C and a fraction (M1) were screened out to be potent inhibitors of 5-LOX. Their anti-inflammatory activities were further investigated and confirmed by RAW 264.7 cells inflammation model and rat foot swelling model. Furthermore, M1 was prepared by MCI GEL CHP20P column chromatography, and further separated by Pre-HPLC. One new compound confirmed to be 5,7,3',4'-tetrahydroxyflavone-7-O-sambubioside was first isolated from LLJT. The results provide a new method for the effective separation of active components derived from natural products.HighlightsA 5-LOX mediated separation method was established for isolation of anti-inflammatory compounds.An anti-inflammatory ingredient was separated by MCI GEL CHP20P column chromatography.One new compound was first isolated from leaves of Lonicera japonica Thunb.5-LOX was immobilised on TiO2 nanotubes and exploited by combining with HPLC-MS system.The anti-inflammatory activity of screened components was evaluated. [Figure: see text].


Asunto(s)
Lonicera , Nanotubos , Animales , Antiinflamatorios/farmacología , Araquidonato 5-Lipooxigenasa , Lonicera/química , Luteolina , Extractos Vegetales/química , Extractos Vegetales/farmacología , Ratas , Titanio
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