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The large surface area, excellent thermal stability and easy modification make microporous organic networks (MONs) good candidates in the field of gas chromatography (GC). Due to the limited species and highly conjugated networks of MONs, their applications are still in infancy and restricted. To accelerate their developments and to enrich their types in GC, here we report the first example of synthesizing alkyl MON and its capillary column for GC separation of position isomers. Linear 1,8-dibromooctane is used as the alkyl monomer instead of traditional aromatic ones to construct novel alkyl MON to decrease the inherent conjugated characteristic of MONs. The alkyl MON exhibits good thermal stability (up to 350°C), large surface area (1173 m2 g-1), and non-polar character, allowing good resolution for alkanes, alkyl benzenes, alcohols, ketones, and diverse position isomers, including dichlorobenzene, trichlorobenzene, bromotoluene, nitrotoluene, methylbenzaldehyde, and ionone with the limits of detection (0.003 mg mL-1) and limits of quantitation of (0.10 mg mL-1). The in situ growth-prepared alkyl MON column demonstrates remarkable duration time and precisions for the retention relative standard deviations, (RSDs%, intra-day, n = 7), 0.06%-0.53% (intra-day, n = 7), and 2.87%-10.59% (column-to-column, n = 3). In addition, the fabricated alkyl MON-coated capillary column offers better resolution than three commercial GC columns for the resolution of methylbenzaldehyde, bromotoluene, and chlorotoluene isomers. This work reveals the practicability for synthesizing alkyl MONs and demonstrates their prospects for position isomers separation.
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Exploring the level of intraspecific diversity in taxa experienced radiation is helpful to understanding speciation and biodiversity assembly. Gentiana section Chondrophyllae sensu lato encompasses more than 180 species and occupies more a half of species in the genus. In this study, we collected samples across the range of three species (Gentiana aristata, G. crassuloides and G. haynaldii) in section Chondrophyllae s.l., and recovered the intra-species variation by comparing with closely related taxon. Using 25 newly sequenced plastid genomes together with previously published data, we compared structural differences, quantified the variations in plastome size, and measured nucleotide diversity in various regions. Our results showed that the plastome size variation in the three Chondrophyllae species ranged from 285 to 628 bp, and the size variation in LSC, IR and SSC ranged from 236 to 898 bp, 52 to 393 bp and 135 to 356 bp, respectively. Nucleotide diversity of plastome or any of the four regions was much higher than the control species. The average nucleotide diversity in plastomes of the three species ranged from 0.0010 to 0.0023 in protein coding genes, and from 0.0023 to 0.0061 in intergenic regions. More repeat sequence variations were detected within the three Chondrophyllae species than the control species. Various plastid sequence matrixes resulted in different backbone topology in two target species, showed uncertainty in phylogenetic relationship based inference. In conclusion, our results recovered that species of G. section Chondrophyllae s.l. has high intraspecific plastome variation, and provided insights into the radiation in this speciose lineage.
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PURPOSE: This study aims to investigate whether contrast-enhanced ultrasound (CEUS) could be used to reveal the status of blood supply of the superficial flap of rat model in the early postoperative stage. METHODS: One viable and one ischemic random-pattern flap were prepared on the left and right back of the same rat respectively with a number of 40. CEUS examinations were applied within 12 h and 7 days postoperatively, and the quantitative measurements of microvascular blood volume (BV) of the base and the end of both flaps were expressed using acoustic intensity as a ratio to that of the healthy skin. RESULTS: Within 12 h post operation, there was a smaller BV value of the ischemic ends than that of both the ischemic bases and viable ends (p < 0.001), while no difference was indicated between ischemic bases and viable bases or between viable bases and viable ends. The same result was provided 7 days post operation. CONCLUSION: Microcirculation of superficial tissues such as random-pattern flaps in this rat model can be assessed quantitatively by CEUS. It could sensitively and accurately reveal the objective status of tissue perfusion in the early postoperative stage.
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Medios de Contraste , Microcirculación , Colgajos Quirúrgicos , Ultrasonografía , Animales , Colgajos Quirúrgicos/irrigación sanguínea , Microcirculación/fisiología , Masculino , Ratas Sprague-Dawley , Ratas , Isquemia/diagnóstico por imagen , Periodo Posoperatorio , Volumen SanguíneoRESUMEN
Conventional solarizing seawater suffers from inefficiency and space constraints. Interfacial solar vapor generation (ISVG) presents an energy-efficient alternative, yet the scalability, adaptability, and durability of a solar evaporator for practical use are remaining concerns. Herein, a hydrogen-bond-repairing solar evaporator featuring reconstructed large-width channels is proposed for ongoing solarization of seawater in ISVG. The polyacrylamide/trehalose/graphene hydrogel (PTGH) exhibits excellent mechanical properties and large-width salt discharge channels. PTGH achieves a notable water evaporation rate of 2.82 kg m-2 h-1 under 1 sun and remains effective even in low-temperature environments. The large-area PTGH is able to continuously operate for solarizing seawater under different conditions, until raw brine is highly concentrated, and eventually solid salt is separated from water. Compared to conventional solarizing seawater, PTGH can save 66.67%-75% of time or land to obtain the same amount of solid salt.
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Stenotaphrum secundatum is an excellent shade-tolerant warm-season turfgrass. Its poor cold resistance severely limits its promotion and application in temperate regions. Mining cold resistance genes is highly important for the cultivation of cold-resistant Stenotaphrum secundatum. Although there have been many reports on the role of the Shaker potassium channel family under abiotic stress, such as drought and salt stress, there is still a lack of research on their role in cold resistance. In this study, the transcriptome database of Stenotaphrum secundatum was aligned with the whole genome of Setaria italica, and eight members of the Shaker potassium channel family in Stenotaphrum secundatum were identified and named SsKAT1.1, SsKAT1.2, SsKAT2.1, SsKAT2.2, SsAKT1.1, SsAKT2.1, SsAKT2.2, and SsKOR1. The KAT3-like gene, KOR2 homologous gene, and part of the AKT-type weakly inwardly rectifying channel have not been identified in the Stenotaphrum secundatum transcriptome database. A bioinformatics analysis revealed that the potassium channels of Stenotaphrum secundatum are highly conserved in terms of protein structure but have more homologous members in the same group than those of other species. Among the three species of Oryza sativa, Arabidopsis thaliana, and Setaria italica, the potassium channel of Stenotaphrum secundatum is more closely related to the potassium channel of Setaria italica, which is consistent with the taxonomic results of these species belonging to Paniceae. Subcellular location experiments demonstrate that SsKAT1.1 is a plasma membrane protein. The expression of SsKAT1.1 reversed the growth defect of the potassium absorption-deficient yeast strain R5421 under a low potassium supply, indicating that SsKAT1.1 is a functional potassium channel. The transformation of SsKAT1.1 into the cold-sensitive yeast strain INVSC1 increased the cold resistance of the yeast, indicating that SsKAT1.1 confers cold resistance. The transformation of SsKAT1.1 into the salt-sensitive yeast strain G19 increased the resistance of yeast to salt, indicating that SsKAT1.1 is involved in salt tolerance. These results suggest that the manipulation of SsKAT1.1 will improve the cold and salt stress resistance of Stenotaphrum secundatum.
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Canales de Potasio de la Superfamilia Shaker , Canales de Potasio de la Superfamilia Shaker/metabolismo , Canales de Potasio de la Superfamilia Shaker/genética , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Poaceae/genética , Poaceae/metabolismo , Frío , Filogenia , Transcriptoma , Arabidopsis/genética , Arabidopsis/metabolismo , Familia de MultigenesRESUMEN
INTRODUCTION: Heat stress poses a severe threat to the growth and production of soybean (Glycine max). Brassinosteroids (BRs) actively participate in plant responses to abiotic stresses, however, the role of BR signaling pathway genes in response to heat stress in soybean remains poorly understood. OBJECTIVES: In this study, we investigate the regulatory mechanisms of GmBSK1 and GmBES1.5 in response to heat stress and the physiological characteristics and yield performance under heat stress conditions. METHODS: Transgenic technology and CRISPR/Cas9 technology were used to generated GmBSK1-OE, GmBES1.5-OE and gmbsk1 transgenic soybean plants, and transcriptome analysis, LUC activity assay and EMSA assay were carried out to elucidate the potential molecular mechanism underlying GmBSK1-GmBES1.5-mediated heat stress tolerance in soybean. RESULTS: CRISPR/Cas9-generated gmbsk1 knockout mutants exhibited increased sensitivity to heat stress due to a reduction in their ability to scavenge reactive oxygen species (ROS). The expression of GmBES1.5 was up-regulated in GmBSK1-OE plants under heat stress conditions, and it directly binds to the E-box motif present in the promoters of abiotic stress-related genes, thereby enhancing heat stress tolerance in soybean plants. Furthermore, we identified an interaction between GmGSK1 and GmBES1.5, while GmGSK1 inhibits the transcriptional activity of GmBES1.5. Interestingly, the interaction between GmBSK1 and GmGSK1 promotes the localization of GmGSK1 to the plasma membrane and releases the transcriptional activity of GmBES1.5. CONCLUSION: Our findings suggest that both GmBSK1 and GmBES1.5 play crucial roles in conferring heat stress tolerance, highlighting a potential strategy for breeding heat-tolerant soybean crops involving the regulatory module consisting of GmBSK1-GmGSK1-GmBES1.5.
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In this work, a fluorescent probe N with aggregation-induced emission effect was synthesized by grafting naphtho[2,3-c]furan-1,3-dione and 2-hydrazinylbenzo[d]thiazole. The probe N could recognize La3+ selectively and sensitively accompanied with an obvious fluorescence and color change from green to blue. Moreover, with the help of AIE properties, probe N achieved the detection of La3+ in the solid state.
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BACKGROUND AND OBJECTIVES: The aim of this study is to establish dosimetric constraints for the brachial plexus at risk of developing grade ≥ 2 brachial plexopathy in the context of stereotactic body radiation therapy (SBRT). PATIENTS AND METHODS: Individual patient data from 349 patients with 356 apical lung malignancies who underwent SBRT were extracted from 5 articles. The anatomical brachial plexus was delineated following the guidelines provided in the atlases developed by Hall, et al. and Kong, et al.. Patient characteristics, pertinent SBRT dosimetric parameters, and brachial plexopathy grades (according to CTCAE 4.0 or 5.0) were obtained. Normal tissue complication probability (NTCP) models were used to estimate the risk of developing grade ≥ 2 brachial plexopathy through maximum likelihood parameter fitting. RESULTS: The prescription dose/fractionation schedules for SBRT ranged from 27 to 60 Gy in 1 to 8 fractions. During a follow-up period spanning from 6 to 113 months, 22 patients (6.3 %) developed grade ≥2 brachial plexopathy (4.3 % grade 2, 2.0 % grade 3); the median time to symptoms onset after SBRT was 8 months (ranged, 3-54 months). NTCP models estimated a 10 % risk of grade ≥2 brachial plexopathy with an anatomic brachial plexus maximum dose (Dmax) of 20.7 Gy, 34.2 Gy, and 42.7 Gy in one, three, and five fractions, respectively. Similarly, the NTCP model estimates the risks of grade ≥2 brachial plexopathy as 10 % for BED Dmax at 192.3 Gy and EQD2 Dmax at 115.4 Gy with an α/ß ratio of 3, respectively. Symptom persisted after treatment in nearly half of patients diagnosed with grade ≥2 brachial plexopathy (11/22, 50 %). CONCLUSIONS: This study establishes dosimetric constraints ranging from 20.7 to 42.7 Gy across 1-5 fractions, aimed at mitigating the risk of developing grade ≥2 brachial plexopathy following SBRT. These findings provide valuable guidance for future ablative SBRT in apical lung malignancies.
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BACKGROUND: Scopolamine has been demonstrated to relieve motion sickness. However, repeated significance testing may increase false-positive results. OBJECTIVES: Review the efficacy and safety of scopolamine in the prevention of motion sickness by performing a meta-analysis with Trial Sequential Analysis (TSA). MATERIAL AND METHODS: Randomized controlled trials (RCTs) compared scopolamine with other medications or placebo were included. Primary outcomes were nausea reported and head movement time. RESULTS: Twenty studies with 753 participants were included. Scopolamine had a greater reported reduction in nausea than placebo (relative risk [RR] 0.35; 95% confidence interval [CI] 0.24 to 0.52; p<0.00001; I2 = 45%), while TSA showed the included sample size exceeded the required information size (RIS). There is no difference in head movement time between scopolamine and placebo (mean difference [MD] 2.02; 95% CI -1.2 to 5.25; p = 0.6; I2 = 0%), while the included sample size did not reach RIS. CONCLUSION: Scopolamine is effective for motion sickness nausea compared to placebo. The TSA recommends conducting more head movement trials to validate the objective efficacy of scopolamine. SIGNIFICANCE: Clarifying the efficacy of scopolamine for motion sickness, the TSA highlights the need for more prospective studies using head movement as an outcome.
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Alzheimer's disease is associated both with imbalances in Al3+ production and changes in viscosity in cells. Their simultaneous measurement could therefore provide valuable insights into Alzheimer's disease pathology. Their simultaneous measurement would therefore be of great value in investigating the pathological mechanism of Alzheimer's disease. We designed a fluorescent probe YM2T with AIE effect that is capable of selectively responding to Al3+ by fluorescence colormetrics and to viscosity by fluorescence "turn on" modes. Additionally, Al3+ and viscosity were simultaneously detected in PC12 cells using the low cytotoxic probe YM2T via blue and green fluorescence channels. More importantly, the YM2T probe was used to image mice with AD. Hence, the YM2T probe shows potential as a useful molecular instrument for studying the pathological impact of Al3+ and viscosity.
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Aluminio , Enfermedad de Alzheimer , Colorantes Fluorescentes , Imagen Óptica , Enfermedad de Alzheimer/diagnóstico por imagen , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Viscosidad , Animales , Células PC12 , Ratones , Aluminio/análisis , Aluminio/química , Estructura Molecular , Ratas , Relación Dosis-Respuesta a Droga , Relación Estructura-Actividad , Modelos Animales de EnfermedadRESUMEN
Pepper (Piper nigrum L.) is a widely used spice plant known for its fruits and roots, which serve as flavor enhancers in culinary applications and hold significant economic value. Despite the popularity of pepper fruits, their roots remain relatively understudied, with limited research conducted on their bioactive components. This study focused on discovering and separating the primary bioactive amide alkaloids found in pepper roots. The process involved using the antioxidant activity of crude fractions and the Global Natural Products Social Molecular Networking analysis platform. The process led to the discovery of 23 previously unknown hydroxyl-amide alkaloids. Notably, compounds 11, 12, and 14 showed excellent antioxidant activity, while compound 11 exhibited significant inhibitory effects on mushroom tyrosinase. Theoretical exploration of enzyme-ligand interactions was conducted through molecular docking and molecular dynamics simulation. The findings of this study highlight the potential of hydroxyl-amide alkaloids as antioxidant products and natural food preservatives in the pharmaceutical and food cosmetic industries.
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Agaricales , Alcaloides , Amidas , Antioxidantes , Inhibidores Enzimáticos , Simulación del Acoplamiento Molecular , Monofenol Monooxigenasa , Piper nigrum , Extractos Vegetales , Raíces de Plantas , Monofenol Monooxigenasa/antagonistas & inhibidores , Monofenol Monooxigenasa/metabolismo , Antioxidantes/química , Antioxidantes/farmacología , Raíces de Plantas/química , Alcaloides/química , Alcaloides/farmacología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacología , Piper nigrum/química , Agaricales/química , Agaricales/enzimología , Amidas/química , Amidas/farmacología , Proteínas Fúngicas/química , Proteínas Fúngicas/antagonistas & inhibidores , Proteínas Fúngicas/metabolismo , Estructura MolecularRESUMEN
BACKGROUND: The Chinese medicine Yangyin Huowei mixture (YYHWM) exhibits good clinical efficacy in the treatment of chronic atrophic gastritis (CAG), but the mechanisms underlying its activity remain unclear. AIM: To investigate the therapeutic effects of YYHWM and its underlying mechanisms in a CAG rat model. METHODS: Sprague-Dawley rats were allocated into control, model, vitacoenzyme, and low, medium, and high-dose YYHWM groups. CAG was induced in rats using N-methyl-N'-nitro-N-nitrosoguanidine, ranitidine hydrochloride, hunger and satiety perturbation, and ethanol gavage. Following an 8-wk intervention period, stomach samples were taken, stained, and examined for histopathological changes. ELISA was utilized to quantify serum levels of PG-I, PG-II, G-17, IL-1ß, IL-6, and TNF-α. Western blot analysis was performed to evaluate protein expression of IL-10, JAK1, and STAT3. RESULTS: The model group showed gastric mucosal layer disruption and inflammatory cell infiltration. Compared with the blank control group, serum levels of PGI, PGII, and G-17 in the model group were significantly reduced (82.41 ± 3.53 vs 38.52 ± 1.71, 23.06 ± 0.96 vs 11.06 ± 0.70, and 493.09 ± 12.17 vs 225.52 ± 17.44, P < 0.01 for all), whereas those of IL-1ß, IL-6, and TNF-α were significantly increased (30.15 ± 3.07 vs 80.98 ± 4.47, 69.05 ± 12.72 vs 110.85 ± 6.68, and 209.24 ± 11.62 vs 313.37 ± 36.77, P < 0.01 for all), and the protein levels of IL-10, JAK1, and STAT3 were higher in gastric mucosal tissues (0.47 ± 0.10 vs 1.11 ± 0.09, 0.49 ± 0.05 vs 0.99 ± 0.07, and 0.24 ± 0.05 vs 1.04 ± 0.14, P < 0.01 for all). Compared with the model group, high-dose YYHWM treatment significantly improved the gastric mucosal tissue damage, increased the levels of PGI, PGII, and G-17 (38.52 ± 1.71 vs 50.41 ± 3.53, 11.06 ± 0.70 vs 15.33 ± 1.24, and 225.52 ± 17.44 vs 329.22 ± 29.11, P < 0.01 for all), decreased the levels of IL-1ß, IL-6, and TNF-α (80.98 ± 4.47 vs 61.56 ± 4.02, 110.85 ± 6.68 vs 89.20 ± 8.48, and 313.37 ± 36.77 vs 267.30 ± 9.31, P < 0.01 for all), and evidently decreased the protein levels of IL-10 and STAT3 in gastric mucosal tissues (1.11 ± 0.09 vs 0.19 ± 0.07 and 1.04 ± 0.14 vs 0.55 ± 0.09, P < 0.01 for both). CONCLUSION: YYHWM reduces the release of inflammatory factors by inhibiting the IL-10/JAK1/STAT3 pathway, alleviating gastric mucosal damage, and enhancing gastric secretory function, thereby ameliorating CAG development and cancer transformation.
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Microscale thermophoresis (MST) is a technique used to measure the strength of molecular interactions. MST is a thermophoretic-based technique that monitors the change in fluorescence associated with the movement of fluorescent-labeled molecules in response to a temperature gradient triggered by an IR LASER. MST has advantages over other approaches for examining molecular interactions, such as isothermal titration calorimetry, nuclear magnetic resonance, biolayer interferometry, and surface plasmon resonance, requiring a small sample size that does not need to be immobilized and a high-sensitivity fluorescence detection. In addition, since the approach involves the loading of samples into capillaries that can be easily sealed, it can be adapted to analyze oxygen-sensitive samples. In this Bio-protocol, we describe the troubleshooting and optimization we have done to enable the use of MST to examine protein-protein interactions, protein-ligand interactions, and protein-nanocrystal interactions. The salient elements in the developed procedures include 1) loading and sealing capabilities in an anaerobic chamber for analysis using a NanoTemper MST located on the benchtop in air, 2) identification of the optimal reducing agents compatible with data acquisition with effective protection against trace oxygen, and 3) the optimization of data acquisition and analysis procedures. The procedures lay the groundwork to define the determinants of molecular interactions in these technically demanding systems. Key features ⢠Established procedures for loading and sealing tubes in an anaerobic chamber for subsequent analysis. ⢠Sodium dithionite (NaDT) could easily be substituted with one electron-reduced 1,1'-bis(3-sulfonatopropyl)-4,4'-bipyridinium [(SPr)2Vâ¢] to perform sensitive biophysical assays on oxygen-sensitive proteins like the MoFe protein. ⢠Established MST as an experimental tool to quantify binding affinities in novel enzyme-quantum dot biohybrid complexes that are extremely oxygen-sensitive.
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Demographic history and mutational load are of paramount importance for the adaptation of the endangered species. However, the effects of population evolutionary history and genetic load on the adaptive potential in endangered conifers remain unclear. Here, using population transcriptome sequencing, whole chloroplast genomes and mitochondrial DNA markers, combined with niche analysis, we determined the demographic history and mutational load for three threatened whitebark pines having different endangered statuses, Pinus bungeana, P. gerardiana and P. squamata. Demographic inference indicated that severe bottlenecks occurred in all three pines at different times, coinciding with periods of major climate and geological changes; in contrast, while P. bungeana experienced a recent population expansion, P. gerardiana and P. squamata maintained small population sizes after bottlenecking. Abundant homozygous-derived variants accumulated in the three pines, particularly in P. squamata, while the species with most heterozygous variants was P. gerardiana. Abundant moderately and few highly deleterious variants accumulated in the pine species that have experienced the most severe demographic bottlenecks (P. gerardiana and P. squamata), most likely because of purging effects. Finally, niche modeling showed that the distribution of P. bungeana might experience a significant expansion in the future, and the species' identified genetic clusters are also supported by differences in the ecological niche. The integration of genomic, demographic and niche data has allowed us to prove that the three threatened pines have contrasting patterns of demographic history and mutational load, which may have important implications in their adaptive potential and thus are also key for informing conservation planning.
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Colorectal cancer (CRC) is a major global health concern, and the development of effective treatment strategies is crucial. Enzyme prodrug therapy (EPT) shows promise in combating tumors but faces challenges in achieving sustained expression of therapeutic enzymes and optimal biological distribution. To address these issues, a fungi-triggered in situ chemotherapeutics generator (named as SC@CS@5-FC) was constructed via oral delivery of a prodrug (5-fluorocytosine, 5-FC) for the treatment of orthotopic colorectal tumor. When SC@CS@5-FC targets the tumor through tropism by Saccharomyces cerevisiae (SC), the chemotherapeutic generator could be degraded under abundant hyaluronidase (HAase) in the tumor microenvironment by an enzyme-responsive gate to release prodrug (5-FC). And nontoxic 5-FC was catalyzed to toxic chemotherapy drug 5-fluorouracil (5-FU) by cytosine deaminase (CD) of SC. Meanwhile, SC and zinc-coordinated chitosan nanoparticles could be used as immune adjuvants to activate antigen-presenting cells and further enhance the therapeutic effect. Our results demonstrated that SC@CS@5-FC could effectively inhibit tumor growth and prolong mouse survival in an orthotopic colorectal cancer model. This work utilizes living SC as a dynamotor and positioning system for the chemotherapeutic generator SC@CS@5-FC, providing a strategy for oral enzyme prodrug therapy for the treatment of orthotopic colorectal.
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Neoplasias Colorrectales , Flucitosina , Fluorouracilo , Inmunoterapia , Profármacos , Saccharomyces cerevisiae , Profármacos/química , Profármacos/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Animales , Ratones , Humanos , Flucitosina/farmacología , Flucitosina/química , Administración Oral , Fluorouracilo/farmacología , Fluorouracilo/química , Fluorouracilo/administración & dosificación , Citosina Desaminasa/metabolismo , Quitosano/química , Antineoplásicos/farmacología , Antineoplásicos/química , Proliferación Celular/efectos de los fármacos , Hialuronoglucosaminidasa/metabolismo , Ratones Endogámicos BALB C , Nanopartículas/química , Ensayos de Selección de Medicamentos AntitumoralesRESUMEN
Postherpetic neuralgia (PHN) is a common, severe, and hard-to-treat chronic pain condition in clinics. Although PHN is developed from herpes zoster (HZ), the developing mechanism is unknown. A previous study investigated blood metabolomic and proteomic profiling in patients with PHN and HZ. The current study aims to explore the blood transcriptomic signature of PHN compared to HZ patients. Whole blood from eight PHN and 15 HZ patients was used for RNA-Seq analysis. There were 82 and 1,788 genes detected specifically in the PHN and HZ groups, respectively. PHN-specific genes are involved in viral infection, lipid and carbohydrate metabolism, and immune response. For genes coexpressed in PHN and HZ patients, there were 407 differential expression genes (DEGs), including 205 upregulated (UP DEGs) and 202 downregulated (DOWN DEGs) in PHN compared to HZ groups. DEGs are involved in viral infection, type I interferon (IFN), and hemoglobin and oxygen carrier activity. UP DEGs are associated with regulatory T cells (Tregs), activated NK cells, and neutrophils, while DOWN DEGs are associated with Tregs, resting NK cells, and monocytes. The results suggest that the metabolism of lipid, glycan, and nucleotides, type I IFN signaling, and altered neutrophil activation are associated with and might contribute to the development of PHN in HZ. It is also suggested that persistent or altered activation of nonspecific immunity may contribute to the development of PHN from HZ.
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Perfilación de la Expresión Génica , Herpes Zóster , Neuralgia Posherpética , Transcriptoma , Humanos , Herpes Zóster/sangre , Herpes Zóster/virología , Neuralgia Posherpética/sangre , Masculino , Femenino , Anciano , Persona de Mediana Edad , Linfocitos T Reguladores/inmunología , Herpesvirus Humano 3/genética , Células Asesinas Naturales/inmunología , Metabolismo de los Lípidos/genéticaRESUMEN
Alzheimer's disease (AD) and osteoporosis (OP) are both serious degenerative diseases, with the potential for concurrent occurrence in clinical settings, and they share certain pathological correlations. Osthole (OST) and notopterol (NOT) are the main active ingredients in traditional Chinese medicine, Angelica pubescens and Notopterygium incisum, respectively, and they exhibit neuroprotective and osteoprotective effects. However, whether the combination of OST and NOT produces a synergistic effect against AD and/or OP remains unclear. The aim of this study was to investigate whether the combination of OST and NOT could produce synergistic anti-AD and/or OP effects using the previously constructed zebrafish AD/OP comorbidity model. Active compounds with anti-AD and OP effects were screened from Angelica pubescens and Notopterygium incisum through network pharmacology, identifying OST and NOT, respectively. Then, the AlCl3-induced (Aluminum chloride, AlCl3) AD combined with OP zebrafish model, in conjunction with the Chou-Talalay synergy evaluation model, was employed to assess whether the OST and NOT combination produced synergistic effects against AD and/or OP. Furthermore, a CuSO4-induced (Copper sulfate, CuSO4) inflammation zebrafish model was used to investigate whether the combination of OST and NOT produced synergistic anti-inflammatory effects, thereby resulting in synergistic anti-AD and/or OP effects. The results demonstrated that the OST-NOT combined treatment produced a synergistic anti-AD and OP effect. Moreover, the combined treatment of OST and NOT significantly inhibited nitric oxide (NO) and reactive oxygen species (ROS) release more effectively than OST or NOT alone, indicating a synergistic anti-inflammatory effect of the OST and NOT combined treatment.
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Enfermedad de Alzheimer , Cumarinas , Modelos Animales de Enfermedad , Sinergismo Farmacológico , Osteoporosis , Pez Cebra , Animales , Cumarinas/farmacología , Cumarinas/uso terapéutico , Enfermedad de Alzheimer/tratamiento farmacológico , Osteoporosis/tratamiento farmacológico , Quimioterapia Combinada , Comorbilidad , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Óxido Nítrico/metabolismoRESUMEN
Cerebral ischemia/reperfusion injury (CIRI) is a common feature of ischemic stroke leading to a poor prognosis. Effective treatments targeting I/R injury are still insufficient. The study aimed to investigate the mechanisms, by which glycyrrhizic acid (18ß-GA) in ameliorates CIRI. Our results showed that 18ß-GA significantly decreased the infarct volume, neurological deficit scores, and pathological changes in the brain tissue of rats after middle cerebral artery occlusion. Western blotting showed that 18ß-GA inhibited the expression levels of phosphorylated JAK2 and phosphorylated STAT3. Meanwhile, 18ß-GA increased LC3-II protein levels in a reperfusion duration-dependent manner, which was accompanied by an increase in the Bcl-2/Bax ratio. Inhibition of 18ß-GA-induced autophagy by 3-methyladenine (3-MA) enhanced apoptotic cell death. In addition, 18ß-GA inhibited the JAK2/STAT3 pathway, which was largely activated in response to oxygen-glucose deprivation/reoxygenation. However, the JAK2/STAT3 activator colivelin TFA abolished the inhibitory effect of 18ß-GA, suppressed autophagy, and significantly decreased the Bcl-2/Bax ratio. Taken together, these findings suggested that 18ß-GA pretreatment ameliorated CIRI partly by triggering a protective autophagy via the JAK2/STAT3 pathway. Therefore might be a potential drug candidate for treating ischemic stroke.
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Autofagia , Infarto de la Arteria Cerebral Media , Janus Quinasa 2 , Fármacos Neuroprotectores , Ratas Sprague-Dawley , Daño por Reperfusión , Factor de Transcripción STAT3 , Transducción de Señal , Animales , Janus Quinasa 2/metabolismo , Janus Quinasa 2/antagonistas & inhibidores , Factor de Transcripción STAT3/metabolismo , Daño por Reperfusión/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Autofagia/efectos de los fármacos , Autofagia/fisiología , Masculino , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Fármacos Neuroprotectores/farmacología , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/metabolismo , Isquemia Encefálica/metabolismo , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/patología , Ácido Glicirrínico/farmacología , Ratas , Apoptosis/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patologíaRESUMEN
Eighteen compounds including eleven previously undescribed diterpenes were isolated from the leaves of Croton mangelong. The structures were determined by HRESIMS, IR, NMR, X-ray diffraction and ECD spectroscopic analysis. All isolates were assayed for their anti-hyperglycemic activities in insulin resistance (IR) 3T3-L1 adipocytes, and compound 4 was tested for its anti-diabetic activity in vivo. Results suggested compound 4 could effectively reduce blood glucose level in diabetic SD rats in a dose of 30 mg/kg.