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MAIN CONCLUSION: The resurrection plant Boea hygrometrica selectively recruits and assembles drought-specific microbial communities across the plant-soil compartments, which may benefit plant growth and fitness under extreme drought conditions. Plant-associated microbes are essential for facilitating plant growth and fitness under drought stress. The resurrection plant Boea hygrometrica in natural habitats with seasonal rainfall can survive rapid desiccation, yet their interaction with microbiomes under drought conditions remains unexplored. This study examined the bacterial and fungal microbiome structure and drought response across plant-soil compartments of B. hygrometrica by high-throughput amplicon sequencing of 16S rRNA gene and internal transcribed spacer. Our results demonstrated that the diversity, composition, and functional profile of the microbial community varied considerably across the plant-soil compartments and were strongly affected by drought stress. Bacterial and fungal diversity was significantly reduced from soil to endosphere and belowground to aboveground compartments. The compartment-specific enrichment of the dominant bacteria phylum Cyanobacteriota and genus Methylorubrum in leaf endosphere, genera Pseudonocardia in rhizosphere soil and Actinoplanes in root endosphere, and fungal phylum Ascomycota in the aboveground compartments and genera Knufia in root endosphere and Cladosporium in leaf endosphere composed part of the core microbiota with corresponding enrichment of beneficial functions for plant growth and fitness. Moreover, the recruitment of dominant microbial genera Sphingosinicella and Plectosphaerella, Ceratobasidiaceae mycorrhizal fungi, and numerous plant growth-promoting bacteria involving nutrient supply and auxin regulation was observed in desiccated B. hygrometrica plants. Our results suggest that the stable assembled drought-specific microbial community of B. hygrometrica may contribute to plant survival under extreme environments and provide valuable microbial resources for the microbe-mediated drought tolerance enhancement in crops.
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Sequías , Microbiota , Microbiología del Suelo , Microbiota/genética , Estrés Fisiológico , Bacterias/genética , Bacterias/clasificación , Raíces de Plantas/microbiología , Raíces de Plantas/genética , ARN Ribosómico 16S/genética , Hongos/fisiología , Hongos/genética , Rizosfera , Brassicaceae/microbiología , Brassicaceae/genética , Brassicaceae/fisiología , Hojas de la Planta/microbiología , Hojas de la Planta/genéticaRESUMEN
BACKGROUND: Ras gene mutation and/or overexpression are drivers in the progression of cancers, including colorectal cancer. Blocking the Ras signaling has become a significant strategy for cancer therapy. Previously, we constructed a recombinant scFv, RGD-p21Ras-scFv by linking RGD membrane-penetrating peptide gene with the anti-p21Ras scFv gene. Here, we expressed prokaryotically RGD-p21Ras-scFv on a pilot scale, then investigated the anti-tumor effect and the mechanism of blocking Ras signaling. METHODS: The E. coli bacteria which could highly express RGD-p21Ras-scFv was screened and grown in 100 L fermentation tank to produce RGD-p21Ras-scFv on optimized induced expression conditions. The scFv was purified from E. coli bacteria using His Ni-NTA column. ELISA was adopted to test the immunoreactivity of RGD-p21Ras-scFv against p21Ras proteins, and the IC50 of RGD-p21Ras-scFv was analyzed by CCK-8. Immunofluorescence colocalization and pull-down assays were used to determine the localization and binding between RGD-p21Ras-scFv and p21Ras. The interaction forces between RGD-p21Ras-scFv and p21Ras after binding were analyzed by molecular docking, and the stability after binding was determined by molecular dynamics simulations. p21Ras-GTP interaction was detected by Ras pull-down. Changes in the MEK-ERK /PI3K-AKT signaling paths downstream of Ras were detected by WB assays. The anti-tumor activity of RGD-p21Ras-scFv was investigated by nude mouse xenograft models. RESULTS: The technique of RGD-p21Ras-scFv expression on a pilot scale was established. The wet weight of the harvested bacteria was 31.064 g/L, and 31.6 mg RGD-p21Ras-scFv was obtained from 1 L of bacterial medium. The purity of the recombinant antibody was above 85%, we found that the prepared on a pilot scale RGD-p21Ras-scFv could penetrate the cell membrane of colon cancer cells and bind to p21Ras, then led to reduce of p21Ras-GTP (active p21Ras). The phosphorylation of downstream effectors MEK-ERK /PI3K-AKT was downregulated. In vivo antitumor activity assays showed that the RGD-p21Ras-scFv inhibited the proliferation of colorectal cancer cell lines. CONCLUSION: RGD-p21Ras-scFv prokaryotic expressed on pilot-scale could inhibited Ras-driven colorectal cancer growth by partially blocking p21Ras-GTP and might be able to be a hidden therapeutic antibody for treating RAS-driven tumors.
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Neoplasias Colorrectales , Escherichia coli , Ratones , Animales , Humanos , Escherichia coli/genética , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Guanosina Trifosfato , Quinasas de Proteína Quinasa Activadas por Mitógenos , Proteínas Proto-Oncogénicas p21(ras)/genéticaRESUMEN
Four high-pressure N-rich compounds (Pmn21-CeN7, Amm2-CeN9, P1Ì-CeN10, and P1Ì-II-CeN10) are proposed using first-principles calculations. Novel polymeric units (a heart shaped layered structure, chain-like N8 rings, and two new banded structures) in four cerium nitrides are reported for the first time in this study. The analyses of electronic structures and bonding properties show that the charge transfer between Ce and N atoms promotes the formation of the Ce-N ionic bond and N-N covalent bond, which play an important role in stabilizing the nitrogen skeleton. Four new phases possess high energy densities (3.24-3.86 kJ g-1), indicating that they are favorable high-energy density materials. Moreover, P1Ì-CeN10 possesses ultra-incompressibility along the [1 0 0] direction. Finally, infrared and Raman spectra are analyzed to provide guidance for experimental synthesis.
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Cross-species transmission of viruses from wildlife animal reservoirs poses a marked threat to human and animal health 1 . Bats have been recognized as one of the most important reservoirs for emerging viruses and the transmission of a coronavirus that originated in bats to humans via intermediate hosts was responsible for the high-impact emerging zoonosis, severe acute respiratory syndrome (SARS) 2-10 . Here we provide virological, epidemiological, evolutionary and experimental evidence that a novel HKU2-related bat coronavirus, swine acute diarrhoea syndrome coronavirus (SADS-CoV), is the aetiological agent that was responsible for a large-scale outbreak of fatal disease in pigs in China that has caused the death of 24,693 piglets across four farms. Notably, the outbreak began in Guangdong province in the vicinity of the origin of the SARS pandemic. Furthermore, we identified SADS-related CoVs with 96-98% sequence identity in 9.8% (58 out of 591) of anal swabs collected from bats in Guangdong province during 2013-2016, predominantly in horseshoe bats (Rhinolophus spp.) that are known reservoirs of SARS-related CoVs. We found that there were striking similarities between the SADS and SARS outbreaks in geographical, temporal, ecological and aetiological settings. This study highlights the importance of identifying coronavirus diversity and distribution in bats to mitigate future outbreaks that could threaten livestock, public health and economic growth.
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Alphacoronavirus/aislamiento & purificación , Alphacoronavirus/patogenicidad , Enfermedades de los Animales/epidemiología , Enfermedades de los Animales/virología , Quirópteros/virología , Infecciones por Coronavirus/veterinaria , Diarrea/veterinaria , Porcinos/virología , Alphacoronavirus/clasificación , Alphacoronavirus/genética , Enfermedades de los Animales/transmisión , Animales , Biodiversidad , China/epidemiología , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Diarrea/patología , Diarrea/virología , Reservorios de Enfermedades/veterinaria , Reservorios de Enfermedades/virología , Genoma Viral/genética , Humanos , Yeyuno/patología , Yeyuno/virología , Filogenia , Síndrome Respiratorio Agudo Grave/epidemiología , Síndrome Respiratorio Agudo Grave/veterinaria , Síndrome Respiratorio Agudo Grave/virología , Análisis Espacio-Temporal , Zoonosis/epidemiología , Zoonosis/transmisión , Zoonosis/virologíaRESUMEN
Pre-exposure of plants to various abiotic conditions confers improved tolerance to subsequent stress. Mild drought acclimation induces acquired rapid desiccation tolerance (RDT) in the resurrection plant Boea hygrometrica, but the mechanisms underlying the priming and memory processes remain unclear. In this study, we demonstrated that drought acclimation-induced RDT can be maintained for at least four weeks but was completely erased after 18 weeks based on a combination of the phenotypic and physiological parameters. Global transcriptome analysis identified several RDT-specific rapid dehydration-responsive genes related to cytokinin and phospholipid biosynthesis, nitrogen and carbon metabolism, and epidermal morphogenesis, most of which were pre-induced by drought acclimation. Comparison of whole-genome DNA methylation revealed dehydration stress-responsive hypomethylation in the CG, CHG, and CHH contexts and acclimation-induced hypermethylation in the CHH context of the B. hygrometrica genome, consistent with the transcriptional changes in methylation pathway genes. As expected, the global promoter and gene body methylation levels were negatively correlated with gene expression levels in both acclimated and dehydrated plants but showed no association with transcriptional divergence during the procedure. Nevertheless, the promoter methylation variations in the CG and CHG contexts were significantly associated with the differential expression of genes required for fundamental genetic processes of DNA conformation, RNA splicing, translation, and post-translational protein modification during acclimation, growth, and rapid dehydration stress response. It was also associated with the dehydration stress-induced upregulation of memory genes, including pre-mRNA-splicing factor 38A, vacuolar amino acid transporter 1-like, and UDP-sugar pyrophosphorylase, which may contribute directly or indirectly to the improvement of dehydration tolerance in B. hygrometrica plants. Altogether, our findings demonstrate the potential implications of DNA methylation in dehydration stress memory and, therefore, provide a molecular basis for enhanced dehydration tolerance in plants induced by drought acclimation.
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Metilación de ADN/genética , Lamiales/genética , Estrés Fisiológico/genética , Transcriptoma/genética , Aclimatación/genética , Aclimatación/fisiología , Deshidratación/genética , Sequías , Regulación de la Expresión Génica de las Plantas/genética , Lamiales/crecimiento & desarrollo , Hojas de la Planta/genética , Hojas de la Planta/crecimiento & desarrollo , Proteínas de Plantas/genéticaRESUMEN
To investigate how effectively systemic immune-inflammation index (SII) and Monocyte-to-HDL-cholesterol ratio (MHR) predict the development of early cardio-cerebral complications in elderly patients who have experienced acute severe carbon monoxide poisoning (ASCMP). A retrospective analysis was conducted on 77 elderly patients with ASCMP admitted to the emergency department of Harrison International Peace Hospital from November 2020 to March 2022. The prevalence of early-onset complications among the 77 individuals was 38.96%. Binary Logistics regression analysis showed that SII and MHR were independent influencing factors of early cardio-cerebral complications in elderly patients with ASCMP. The complication group had a longer length of stay, a greater mortality rate, and a higher incidence of delayed encephalopathy after acute carbon monoxide poisoning (p < .05) than the non-complication group. The area under the curve (AUC) of SII and MHR in predicting early cardio-cerebral complications in elderly patients with ASCMP were 0.724 and 0.796, respectively, with 80.0% and 63.3% sensitivity, and 61.7% and 87.2% specificity. The incidence of early cardio-cerebral complications in elderly patients who had ASCMP is high and the prognosis is poor. SII and MHR can be utilized as independent predictors of early cardio-cerebral complications in elderly patients with ASCMP, allowing doctors to diagnose and treat cardio-cerebral complications earlier and improve prognosis.
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Intoxicación por Monóxido de Carbono , HDL-Colesterol , Monocitos , Humanos , Intoxicación por Monóxido de Carbono/sangre , Intoxicación por Monóxido de Carbono/complicaciones , Intoxicación por Monóxido de Carbono/inmunología , Anciano , Masculino , Femenino , Estudios Retrospectivos , Pronóstico , Monocitos/inmunología , HDL-Colesterol/sangre , Anciano de 80 o más Años , Inflamación/sangre , Inflamación/inmunología , Encefalopatías/inmunología , Encefalopatías/sangre , Encefalopatías/epidemiología , Persona de Mediana Edad , Enfermedades Cardiovasculares/inmunología , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/sangreRESUMEN
Objective To explore the influence of Linggui Zhugan Decoction (LGZGD) on high glucose induced podocyte autophagy Methods LGZGD containing serum were prepared by intragastric administation of 4.2 g·kg-1 (low dose), 8.4 g·kg-1 (medium dose), and 12.6 g·kg-1 (high dose) LGZGD into SD rats respectively. MPC5 and AB8/13 cells were treated with 60 mmol/L glucose to establish diabetic nephropathy podocyte model in vitro. Podocytes, MPC5 and AB8.13, were divided into control group, high glucose group, low dose LGZGD group, medium dose LGZGD group, and high dose LGZGD group, respectively. For the three LGZGD groups, before LGZGD intervention, podocytes were treated with 60 mmol/L glucose for 3 days. After treated with LGZGD containing serum, cells were collected to analyze cell migration using Transwell assay, proliferation using CCK8, apoptosis and cell cycle using flow cytometry,, autophagosome formation using transmission electron microscopy, and expression levels of Beclin-1, Atg5, LC3II/I, and P62 proteins using western blot.Results Compared with the control group, the proliferation and migration of MPC5 and AB8.13 cells in high glucose group showed slightly decreased, whereas these parameters restored after intervention with low and medium concentrations of LGZGD, with the medium dose LGZGD having the best effect. Flow cytometry analysis showed that the medium dose LGZGD group had a lower apoptosis rate (P < 0.05) and higher survival rate (P > 0.05) compared to the high dose group. High glucose arrested podocytes in G1 phase, whereas LGZGD shifted podocytes from being predominant in G1 phase to increasing into G2. High dose LGZGD significanly reduced increased autophagosome formation due to high glucose in both podocytes (P < 0.05). Western blot analysis showed that Beclin-1, Atg5, LC3â ¡/â , and P62 expressions were increased in MPC5 cells treated with high glucose, and reversed after adminstration of low and medium doses of LGZGD (P < 0.05). Conclusion LGZGD reduced apoptosis and enhanced autophagy in high glucose treated podocytes via regulating Beclin-1/LC3II/I/Atg5 expression.
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To comprehensively reveal and utilize the plant resources of Lycium in China, this study determined and compared the content of monosaccharides, polysaccharides, proteins, carotenoids, organic acids, and phenols in the dried fruits of 8 different Lycium species. Furthermore, the traits including the hundred-fruit weight, shape index, and the ratio of seed to fruit were measured, and the correlations between the content of chemical compounds and fruit traits were assessed. The results showed that L. truncatum, L. barbarum var. auranticarpum, and L. dasystemum var. rubricaulium were the species with high content of monosaccharides. L. barbarum and L. barbarum var. auranticarpum were the species with high content of total polysaccharides, and L. barbarum was the species with high content of carotenoids. L. yunnanense and L. chinense var. potaninii had high content of soluble proteins. L. truncatum, L. dasystemum, and L. barbarum showed high content of organic acids and phenols. L. barbarum and L. barbarum var. auranticarpum demonstrated high fruit weight, while L. yunnanense and L. chinense had high ratios of seed to fruit. The multivariate statistical analysis indicated that polysaccharides, carotenoids, hundred-fruit weight, ratio of seed to fruit, scopolamine, fructose, 5-O-feruloylquinic acid, kaempferol-3-O-rutinoside, scopoletin, cryptochlorogenic acid, and caffeic acid were the main differential compounds in the fruits among different species of Lycium. Moreover, the results of correlation ananysis showed strong correlations between fruit traits and compound content. Specifically, the hundred-fruit weight had positive correlations with the content of total polysaccharides and scopola-mine. The ratio of seed to fruit was negatively correlated with the content of rutin, kaempferol-3-O-rutinoside, fructose, and glucose and positively correlated with the content of succinic acid, soluble proteins, and zeaxanthin. The results implied that chemical compounds presented different distribution patterns in the fruits of 8 Lycium species. This study provides a basis for the comprehensive development and utilization, targeted breeding, and value-added application of Lycium plants.
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Carotenoides , Frutas , Lycium , Lycium/química , Lycium/crecimiento & desarrollo , Frutas/química , Frutas/crecimiento & desarrollo , Carotenoides/análisis , Fenoles/análisis , Polisacáridos/análisis , Polisacáridos/química , Monosacáridos/análisis , China , Proteínas de Plantas/análisisRESUMEN
The study investigated the protective effect and mechanism of 2-phenylethyl-beta-glucopyranoside(Phe) from Huaizhong No.1 Rehmannia glutinosa on hypoxic pulmonary hypertension(PH), aiming to provide a theoretical basis for clinical treatment of PAH. Male C57BL/6N mice were randomly divided into normal group, model group, positive drug(bosentan, 100 mg·kg~(-1)) group, and low-and high-dose Phe groups(20 and 40 mg·kg~(-1)). Except for the normal group, all other groups were continuously subjected to model induction in a 10% hypoxic environment for 5 weeks, with oral administration for 14 days starting from the 3rd week. The cardiopulmonary function, right ventricular pressure, cough and asthma index, lung injury, cell apoptosis, oxidative stress-related indicators, immune cells, and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)/hypoxic inducible factor 1α(HIF-1α) pathway-related proteins or mRNA levels were examined. Furthermore, hypoxia-induced pulmonary arterial smooth muscle cell(PASMC) were used to further explore the mechanism of Phe intervention in PH combined with PI3K ago-nist(740Y-P). The results showed that Phe significantly improved the cardiopulmonary function of mice with PH, decreased right ventricular pressure, cough and asthma index, and lung injury, reduced cell apoptosis, oxidative stress-related indicators, and nuclear levels of phosphorylated Akt(p-Akt) and phosphorylated mTOR(p-mTOR), inhibited the expression levels of HIF-1α and PI3K mRNA and proteins, and maintained the immune cell homeostasis in mice. Further mechanistic studies revealed that Phe significantly reduced the viability and migration ability of hypoxia-induced PASMC, decreased the expression of HIF-1α and PI3K proteins and nuc-lear levels of p-Akt and p-mTOR, and this effect was blocked by 740Y-P. Therefore, it is inferred that Phe may exert anti-PH effects by alleviating the imbalance of oxidative stress and apoptosis in lung tissues and regulating immune levels, and its mechanism may be related to the regulation of the PI3K/Akt/mTOR/HIF-1α pathway. This study is expected to provide drug references and research ideas for the treatment of PH.
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Glucósidos , Hipertensión Pulmonar , Subunidad alfa del Factor 1 Inducible por Hipoxia , Hipoxia , Ratones Endogámicos C57BL , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Rehmannia , Serina-Treonina Quinasas TOR , Animales , Masculino , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Ratones , Hipertensión Pulmonar/tratamiento farmacológico , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/metabolismo , Hipertensión Pulmonar/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Rehmannia/química , Fosfatidilinositol 3-Quinasas/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Glucósidos/farmacología , Hipoxia/tratamiento farmacológico , Hipoxia/fisiopatología , Hipoxia/metabolismo , Transducción de Señal/efectos de los fármacos , Humanos , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/química , Apoptosis/efectos de los fármacosRESUMEN
Immunotherapy has pioneered a new era of tumor treatment, in which the immune checkpoint blockade (ICB) exerts significant superiority in overcoming tumor immune escape. However, the formation of an immune-suppressive tumor microenvironment (TME) and the lack of effective activation of the immune response have become major obstacles limiting its development. Emerging reports indicate that cancer stem cells (CSCs) potentially play important roles in treatment resistance and progressive relapse, while current research is usually focused on CSCs themselves. In this review, we mainly emphasize the collusions between CSCs and tumor-infiltrating immune cells. We focus on the summary of CSC-immune cell crosstalk signaling pathways in ICB resistance and highlight the application of targeted drugs to improve the ICB response.
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Neoplasias , Humanos , Neoplasias/patología , Inmunoterapia , Escape del Tumor , Transducción de Señal , Células Madre Neoplásicas/metabolismo , Microambiente TumoralRESUMEN
Neuronal apoptosis has been found to have a pivotal role in the course of Alzheimer's disease (AD). Berberine (BBR), a potent antioxidant, occurs in plants such as Berberis, Phellodendron chinense, and Hydrastis canadensis. In this study, a neuronal apoptotic model was established in vitro using HT22 cells induced by Aß25-35 to explore whether BBR contributes to protecting neurons against Aß25-35-induced neurotoxicity, as well as its potential mechanisms. BBR was applied to HT22 cells for 1 h prior to exposing the cells to Aß25-35 for 24 h. A CCK-8 assay was utilized to assess cell viability, and Annexin V - fluorescein isothiocyanate (FITC)/propidium iodide and Hoechst 33342 fluorescence staining were used to measure the rate of cell apoptosis. Existing scientific literature was also reviewed to further determine the effects of BBR on ROS production and mitochondrial function in HT22 cells. Furthermore, the expressions of proteins, including cytochrome C, cleaved caspase-3, p-p65, p65, and Nrf2/HO-1 antioxidant axis were assessed by Western blotting. The data indicated that BBR markedly improved cell viability, inhibited apoptosis and intracellular ROS levels, improved mitochondrial membrane potentials, decreased the rate of p-p65/p65, cytochrome C, and cleaved caspase-3, and intensified the activity of Nrf2/HO-1 antioxidants in HT22 cells. Overall, the findings indicated that BBR provides a certain level of neuroprotectiveness in HT22 cells exposed to Aß25-35 via relieving oxidative stress, as well as by restraining the mitochondrial pathway of cellular apoptosis. In addition, the restraint of NF-κB activity and sensitization of the Nrf2/HO-1 antioxidant axis, which together are intimately involved in the neuroprotection of BBR, may be possible mechanisms accounting for its effectiveness against Aß25-35in vitro.
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Berberina , Fármacos Neuroprotectores , Antioxidantes/farmacología , Antioxidantes/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Berberina/farmacología , Especies Reactivas de Oxígeno/metabolismo , Caspasa 3/metabolismo , Péptidos beta-Amiloides/toxicidad , Péptidos beta-Amiloides/metabolismo , Transducción de Señal , Citocromos c/metabolismo , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo , ApoptosisRESUMEN
Previous studies have shown mitochondrial dysfunction in various acute kidney injuries and chronic kidney diseases. Lipoic acid exerts potent effects on oxidant stress and modulation of mitochondrial function in damaged organ. In this study we investigated whether alpha lipoamide (ALM), a derivative of lipoic acid, exerted a renal protective effect in a type 2 diabetes mellitus mouse model. 9-week-old db/db mice were treated with ALM (50 mg·kg-1·d-1, i.g) for 8 weeks. We showed that ALM administration did not affect blood glucose levels in db/db mice, but restored renal function and significantly improved fibrosis of kidneys. We demonstrated that ALM administration significantly ameliorated mitochondrial dysfunction and tubulointerstitial fibrotic lesions, along with increased expression of CDX2 and CFTR and decreased expression of ß-catenin and Snail in kidneys of db/db mice. Similar protective effects were observed in rat renal tubular epithelial cell line NRK-52E cultured in high-glucose medium following treatment with ALM (200 µM). The protective mechanisms of ALM in diabetic kidney disease (DKD) were further explored: Autodock Vina software predicted that ALM could activate RXRα protein by forming stable hydrogen bonds. PROMO Database predicted that RXRα could bind the promoter sequences of CDX2 gene. Knockdown of RXRα expression in NRK-52E cells under normal glucose condition suppressed CDX2 expression and promoted phenotypic changes in renal tubular epithelial cells. However, RXRα overexpression increased CDX2 expression which in turn inhibited high glucose-mediated renal tubular epithelial cell injury. Therefore, we reveal the protective effect of ALM on DKD and its possible potential targets: ALM ameliorates mitochondrial dysfunction and regulates the CDX2/CFTR/ß-catenin signaling axis through upregulation and activation of RXRα. Schematic figure illustrating that ALM alleviates diabetic kidney disease by improving mitochondrial function and upregulation and activation of RXRα, which in turn upregulated CDX2 to exert an inhibitory effect on ß-catenin activation and nuclear translocation. RTEC renal tubular epithelial cell. ROS Reactive oxygen species. RXRα Retinoid X receptor-α. Mfn1 Mitofusin 1. Drp1 dynamic-related protein 1. MDA malondialdehyde. 4-HNE 4-hydroxynonenal. T-SOD Total-superoxide dismutase. CDX2 Caudal-type homeobox transcription factor 2. CFTR Cystic fibrosis transmembrane conductance regulator. EMT epithelial mesenchymal transition. α-SMA Alpha-smooth muscle actin. ECM extracellular matrix. DKD diabetic kidney disease. Schematic figure was drawn by Figdraw ( www.figdraw.com ).
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Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Ácido Tióctico , Animales , Ratones , Ratas , beta Catenina/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/patología , Transición Epitelial-Mesenquimal , Fibrosis/tratamiento farmacológico , Fibrosis/metabolismo , Glucosa/metabolismo , Riñón/patología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Ácido Tióctico/farmacología , Ácido Tióctico/uso terapéutico , Receptor alfa X Retinoide/efectos de los fármacos , Receptor alfa X Retinoide/metabolismoRESUMEN
BACKGROUND: Unhealthy gestational weight gain is a modifiable risk factor for adverse maternal and child health. Appropriate and effective intervention strategies that focus on behavioral change or maintenance are critical in weight management during pregnancy. Our aim was to uncover the influencing factors and psychosocial mechanisms of gestational weight control behavior, and to construct a behavioral model suitable for intervention based on Information-Motivation-Behavioral skills (IMB) model. METHODS: A sample of 559 pregnant women from a municipal maternal and child healthcare facility in Jiangsu Province, China was enrolled in this cross-sectional empirical study. Partial least square structural equation modelling was used to verify the hypothesized model, and post hoc analyses was used to test the effect of parity and pre-pregnancy BMI on the model. RESULTS: The IMB model elements can predict gestational weight management (GWM) behavior well, with information being the most influential factor. As predicted, information affects GWM directly (ß = 0.325, p < 0.05) and indirectly (ß = 0.054, p < 0.05) through behavioral skills. Likewise, motivation has direct (ß = 0.461, p < 0.05) effects on GWM, and has indirect (ß = 0.071, p < 0.05) effects through behavioral skills. Behavioral skills have a direct impact (ß = 0.154, p < 0.05). The model had a goodness of fit (GOF = 0.421) and was robust when tested in subgroups of different parity or pre-pregnancy BMI. CONCLUSION: Findings from this study supported the predictions of the IMB model for GWM behavior, and identified its modifiable determinants. The tested behavior model for GWM can serve as a new validated intervention strategy in weight management among pregnant women.
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Modelo de Habilidades de Información Motivación Comportamiento , Motivación , Embarazo , Niño , Humanos , Femenino , Estudios Transversales , Conductas Relacionadas con la Salud , ChinaRESUMEN
Treatment of epithelial ovarian cancer (EOC) is a challenge because it still leads to unsatisfactory clinical prognosis. This is due to the toxicity and poor targeting of chemotherapeutic agents, as well as metastasis of the tumor. In this study, we designed a targeted liposome with nanostructures to overcome these problems. In the liposomes, epirubicin and curcumin were encapsulated to achieve their synergistic antitumor efficacy, while Epi-1 was modified on the liposomal surface to target epithelial cell adhesion molecule (EpCAM). Epi-1, a macrocyclic peptide, exhibits active targeting for enhanced cellular uptake and potent cytotoxicity against tumor cells. The encapsulation of epirubicin and curcumin synergistically inhibited the formation of neovascularization and vasculogenic mimicry (VM) channels, thereby suppressing tumor metastasis on SKOV3 cells. The dual drug loaded Epi-1-liposomes also induced apoptosis and downregulated metastasis-related proteins for effective antitumor in vitro. In vivo studies showed that dual drug loaded Epi-1-liposomes prolonged circulation time in the blood and increased the selective accumulation of drug at the tumor site. H&E staining and immunohistochemistry with Ki-67 also showed that targeted liposomes elevated antitumor activity. Also, targeted liposomes downregulated angiogenesis-related proteins to inhibit angiogenesis and thus tumor metastasis. In conclusion, the production of dual drug loaded Epi-1-liposomes is an effective strategy for the treatment of EOC.
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Curcumina , Neoplasias Ováricas , Humanos , Femenino , Epirrubicina/farmacología , Epirrubicina/química , Epirrubicina/uso terapéutico , Liposomas/química , Molécula de Adhesión Celular Epitelial , Curcumina/farmacología , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Línea Celular Tumoral , Neoplasias Ováricas/tratamiento farmacológicoRESUMEN
A phytochemical investigation of the steroidal saponins from the rhizomes of Paris polyohylla var. latifolia led to the discovery and characterization of three new spirostanol saponins, papolatiosides A-C (1-3), and nine known compounds (4-12). Their structures were established via extensive spectroscopic data analysis and chemical methods. Interestingly, compounds 1 and 2 possessed a fructosyl in their oligosaccharide moiety, which is rare in natural product and was firstly reported in family Melanthiaceae. The cytotoxicity of these saponins against several human cancer cell lines was evaluated by a CCK-8 experiment. As a result, compound 1 exhibited a significant cytotoxic effect on LN229, U251, Capan-2, HeLa, and HepG2 cancer cells with IC50 values of 4.18 ± 0.31, 3.85 ± 0.44, 3.26 ± 0.34, 3.30 ± 0.38 and 4.32 ± 0.51 µM, respectively. In addition, the result of flow cytometry analysis indicated that compound 1 could induce apoptosis of glioma cells LN229. The underlying mechanism was explored by network pharmacology and western bolt experiments, which indicated that compound 1 could induce glioma cells LN229 apoptosis by regulating the EGFR/PI3K/Akt/mTOR pathway.
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Antineoplásicos , Glioma , Liliaceae , Melanthiaceae , Saponinas , Humanos , Rizoma/química , Fosfatidilinositol 3-Quinasas , Liliaceae/química , Antineoplásicos/análisis , Saponinas/farmacología , Saponinas/químicaRESUMEN
Metabolic associated fatty liver disease (MAFLD) has become a prevalent chronic liver disease worldwide because of lifestyle and dietary changes. Gut microbiota and its metabolites have been shown to play a critical role in the pathogenesis of MAFLD. Understanding of the function of gut microbiota and its metabolites in MAFLD may help to elucidate pathological mechanisms, identify diagnostic markers, and develop drugs or probiotics for the treatment of MAFLD. Here we review the pathogenesis of MAFLD by gut microbiota and its metabolites and discuss the feasibility of treating MAFLD from the perspective of gut microbes.
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Hígado Graso , Microbioma Gastrointestinal , Hígado Graso/microbiología , HumanosRESUMEN
This study aimed to investigate the effect and underlying mechanism of Poria cocos polysaccharides(PCP) on myocardial cell apoptosis in the rat model of myocardial ischemia-reperfusion injury(MI/RI). Male SPF-grade SD rats were randomly divided into a sham group(saline), a model group(saline), low-and high-dose PCP groups(100 and 200 mg·kg~(-1)), and a fasudil group(10 mg·kg~(-1)), with 16 rats in each group. Except for the sham group, the other four groups underwent left anterior descending coronary artery ligation for 30 min followed by reperfusion for 2 h to establish the MI/RI model. The myocardial infarct area was assessed by TTC staining. Histological changes were observed through HE staining. Myocardial cell apoptosis was evaluated using TUNEL staining. Serum lactate dehydrogenase(LDH), creatine kinase MB(CK-MB), interleukin-1ß(IL-1ß) and IL-18 levels, myocardial superoxide dismutase(SOD) activity and malondialdehyde(MDA) levels were detected by ELISA. Protein expression of B-cell lymphoma 2(Bcl-2), Bcl-2 associated X protein(Bax), cleaved caspase-3, Ras homolog gene A(RhoA), myosin phosphatase target subunit 1(MYPT-1), phosphorylated MYPT-1(p-MYPT-1), and Rho-associated coiled-coil forming kinase 1(ROCK 1) were measured by Western blot. Pathological staining of myocardial tissue revealed that in the model group, there was focal necrosis of myocardial tissue, myocardial cell swelling, unclear boundaries, and neutrophil infiltration. These pathological changes were alleviated in the low-and high-dose PCP groups and the fasudil group. Compared with the model group, the low-and high-dose PCP groups and the fasudil group showed significantly reduced myocardial infarct area and myocardial cell apoptosis rate. Compared with the sham group, the model group exhibited elevated serum LDH, CK-MB, IL-1ß and IL-18 levels, increased MDA levels, relative protein expression of Bax, cleaved caspase-3, RhoA, ROCK1 and p-MYPT-1, and decreased myocardial SOD levels and Bcl-2 protein expression. Compared with the model group, the PCP groups and the fasudil group showed lowered serum LDH, CK-MB, IL-1ß and IL-18 levels, decreased MDA levels, relative protein expression of Bax, cleaved caspase-3, RhoA, ROCK1 and p-MYPT-1, and increased myocardial SOD levels and Bcl-2 protein expression. PCP exhibited a certain preventive effect on myocardial tissue pathological damage and myocardial cell apoptosis in MI/RI rats, possibly related to the inhibition of the Rho-ROCK signaling pathway activation, thereby reducing oxidative stress and inflammatory responses.
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1-(5-Isoquinolinesulfonil)-2-Metilpiperazina/análogos & derivados , Infarto del Miocardio , Daño por Reperfusión Miocárdica , Wolfiporia , Ratas , Masculino , Animales , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Proteína X Asociada a bcl-2/metabolismo , Ratas Sprague-Dawley , Caspasa 3/metabolismo , Interleucina-18 , Transducción de Señal , Infarto del Miocardio/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Forma MB de la Creatina-Quinasa , Apoptosis , Polisacáridos/farmacología , Superóxido Dismutasa/metabolismoRESUMEN
BACKGROUND AND AIMS: This study aimed to identify unique dietary patterns, and to examine the correlation of dietary patterns with elevated blood pressure, lipid profile and fasting plasma glucose (FPG) among adults in Jiangsu Province of China. METHODS AND RESULTS: 4951 individuals were selected in this cross-sectional study from nutrition and health survey in Jiangsu Province in 2014. Factor analysis was used to identify the dietary patterns. Higher quartile of the cereals-seafood-dairy dietary pattern was inversely associated with high low-density lipoprotein cholesterol (LDL) (composed to Q1, OR = 0.834, 95% CI: 0.700â¼0.993, P < 0.05) and FPG (composed to Q1, OR = 0.725, 95% CI: 0.609-0.862, P < 0.05), while higher quartile of the traditional Jiangsu dietary pattern was positively associated with low high-density lipoprotein cholesterol (HDL) (composed to Q1, OR = 1.395, 95% CI: 1.067â¼1.825, P < 0.05) and high systolic blood pressure (SBP) (composed to Q1, OR = 1.238, 95% CI: 1.020â¼1.503, P < 0.05). Higher scores of the refined food-oriented dietary pattern was inversely related to high triglycerides (TG) (composed to Q1, OR = 0.665, 95% CI: 0.551â¼0.802, P < 0.05), but was positively related to high TC (composed to Q1, OR = 2.179, 95% CI: 1.817â¼2.614), high LDL (composed to Q1, OR = 2.431, 95% CI: 2.037â¼2.902, P < 0.05) and elevated FPG (composed to Q1, OR = 1.734, 95% CI: 1.458â¼2.061, P < 0.05). CONCLUSION: Different structure of dietary patterns do affect the blood pressure, lipid profile and fasting plasma glucose among adults in Jiangsu Province, China.
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Glucemia , Ayuno , Adulto , Presión Sanguínea , China/epidemiología , HDL-Colesterol , Estudios Transversales , Humanos , Factores de Riesgo , TriglicéridosRESUMEN
Clostridioides difficile is the predominant pathogen responsible for antimicrobial associated diarrhea (AAD) and health care facility-associated infectious diarrhea. The role of C. difficile in China and its impact on public health have gained attention in recent years. Most clinical C. difficile isolates in China belong to multilocus sequence type clade 1 with sequence types (STs) 3, 35 and 54 predominating. Of note, the proportion of C. difficile isolates from clade 4, especially ST37 (PCR ribotype 17), is much higher in China than in other areas. In China, the antimicrobial-resistance profile of C. difficile is similar to that of other countries, demonstrating a higher resistance rate to erythromycin, clindamycin, and fluoroquinolones (ciprofloxacin, levofloxacin, and moxifloxacin). In general, susceptibility to vancomycin and metronidazole of clinical C. difficile in China is high, however, some resistance to metronidazole have recently been reported. Preclinical research on C. difficile in animals in China is limited, and different studies have reported varied isolation rates and antimicrobial resistance profiles. The diverse molecular types of C. difficile in China merit further epidemiological, genomic and evolutionary investigation. While the use of probiotics in preventing C. difficile infection (CDI) have received both support and opposition, the discovery of new probiotics and new formulations are showing promising results in combating the threat posed by CDI.
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Antiinfecciosos , Clostridioides difficile , Infecciones por Clostridium , Infección Hospitalaria , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , China/epidemiología , Clostridioides difficile/genética , Infecciones por Clostridium/tratamiento farmacológico , Infecciones por Clostridium/epidemiología , Infección Hospitalaria/tratamiento farmacológico , Diarrea/tratamiento farmacológico , Farmacorresistencia Bacteriana/genética , Humanos , Metronidazol/farmacología , Metronidazol/uso terapéutico , Pruebas de Sensibilidad Microbiana , RibotipificaciónRESUMEN
PURPOSE: Design an extended osteotomy guide (EOG) for Le Fort I osteotomy to improve the safety of surgery. MATERIALS AND METHODS: The digital Le Fort I osteotomy guide was designed in MIMICS 23.0. Twenty-eight patients were randomized into 2 groups. Patients in the experimental group used EOG, and patients in the control group used a traditional osteotomy guide (TOG). Virtual designs and actual postoperative outcomes were compared by cone-beam computed tomography. The safety of the operation was confirmed by the accuracy of the osteotomy direction and depth on the inner and posterior walls of the maxilla. RESULTS: All positioning deviations of both osteotomy guides were <0.3 mm (P>0.05). The osteotomy depths on the inner and posterior walls with the EOG and TOG deviated by 0.789±1.179 and 1.811±1.345 mm (P=0.004) and 0.648±0.999 and 1.262±0.942 mm (P=0.030), respectively. The angles of deviation of the osteotomy direction on the inner and posterior walls by the EOG and TOG were 2.025±2.434 and 5.069±2.391 degrees (P<0.001) and 2.772±2.979 and 8.653±4.690 degrees (P<0.001), respectively. CONCLUSIONS: The EOG was more accurate than TOG for manipulating osteotomy direction and depth on the inner and posterior maxillary walls. Thus, EOG could ensure higher surgical safety than TOG.