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This study aims to investigate the effect and mechanism of Maxingshigan Decoction on inflammation in the rat model of cough variant asthma(CVA). The SPF-grade SD rats of 6-8 weeks were randomized into normal, model, Montelukast sodium, and low-, medium-, and high-dose Maxing Shigan Decoction groups, with 8 rats in each group. The CVA rat model was induced by ovalbumin(OVA) and aluminum hydroxide sensitization and ovalbumin stimulation. The normal group and model group were administrated with equal volume of normal saline by gavage, and other groups with corresponding drugs by gavage. After the experiment, the number of white blood cells in blood and the levels of interleukin-6(IL-6), interleukin-10(IL-10), and tumor necrosis factor-α(TNF-α) in the serum were measured. The lung tissue was stained with hematoxylin-eosin(HE). Western blot was employed to determine the protein levels of nuclear factor-κB(NF-κB), Toll-like receptor 4(TLR4), myeloid differentiation protein(MyD88), and mitogen-activated protein kinase(MAPK) in the lung tissue. Real-time PCR was carried out to measure the mRNA levels of TLR4 and MyD88 in the lung tissue. Compared with the normal group, the model group showed increased white blood cells, elevated IL-6 and TNF-α levels(P<0.01), lowered IL-10 level(P<0.01), up-regulated protein levels of TLR4, MyD88, p-p65/NF-κB p65, and p-p38 MAPK/p38 MAPK(P<0.01) and mRNA levels of TLR4 and MyD88(P<0.01) in the lung tissue. HE staining showed obvious infiltration of inflammatory cells around the airway and cell disarrangement in the model group. Compared with the model group, Montelukast sodium and high-dose Maxing Shigan Decoction reduced the white blood cells, lowered the IL-6 and TNF-α levels(P<0.01), and elevated the IL-10 level(P<0.01). Moreover, they down-regulated the protein levels of TLR4, MyD88, p-p65/NF-κB p65, p-p38 MAPK/p38 MAPK in the lung tissue(P<0.01) and the mRNA levels of TLR4 and MyD88 in the lung tissue(P<0.01). HE staining showed that Montelukast sodium and high-dose Maxing Shigan Decoction reduced inflammatory cell infiltration and cell disarrangement. The number of white blood cells, the levels of IL-10 and TNF-α in the serum, the protein levels of TLR4, MyD88, p-p65/NF-κB p65, and p-p38 MAPK/p38 MAPK, and the mRNA levels of TLR4 and MyD88 in the lung tissue showed no significant differences between the Montelukast sodium group and high-dose Maxing Shigan Decoction group. Maxing Shigan Decoction can inhibit airway inflammation in CVA rats by inhibiting the activation of TLR4/MyD88/NF-κB and p38 MAPK signaling pathways.
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Acetatos , Asma Variante con Tos , Ciclopropanos , FN-kappa B , Quinolinas , Sulfuros , Ratas , Animales , FN-kappa B/genética , FN-kappa B/metabolismo , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Interleucina-10/genética , Transducción de Señal , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Ratas Sprague-Dawley , Ovalbúmina , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismo , Inflamación , Proteínas Quinasas p38 Activadas por Mitógenos/genética , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , ARN MensajeroRESUMEN
Alternative polyadenylation (APA) enables a gene to generate multiple transcripts with different 3' ends, which is dynamic across different cell types or conditions. Many computational methods have been developed to characterize sample-specific APA using the corresponding RNA-seq data, but suffered from high error rate on both polyadenylation site (PAS) identification and quantification of PAS usage (PAU), and bias toward 3' untranslated regions. Here we developed a tool for APA identification and quantification (APAIQ) from RNA-seq data, which can accurately identify PAS and quantify PAU in a transcriptome-wide manner. Using 3' end-seq data as the benchmark, we showed that APAIQ outperforms current methods on PAS identification and PAU quantification, including DaPars2, Aptardi, mountainClimber, SANPolyA, and QAPA. Finally, applying APAIQ on 421 RNA-seq samples from liver cancer patients, we identified >540 tumor-associated APA events and experimentally validated two intronic polyadenylation candidates, demonstrating its capacity to unveil cancer-related APA with a large-scale RNA-seq data set.
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Neoplasias , Transcriptoma , Humanos , Poliadenilación , RNA-Seq , Análisis de Secuencia de ARN/métodos , Neoplasias/genética , Regiones no Traducidas 3'RESUMEN
Recent studies have revealed that neural functions are involved in possibly every aspect of a cancer development, serving as bridges connecting microenvironmental stressors, activities of intracellular subsystems, and cell survival. Elucidation of the functional roles played by the neural system could provide the missing links in developing a systems-level understanding of cancer biology. However, the existing information is highly fragmented and scattered across the literature and internet databases, making it difficult for cancer researchers to use. We have conducted computational analyses of transcriptomic data of cancer tissues in TCGA and tissues of healthy organs in GTEx, aiming to demonstrate how the functional roles by the neural genes could be derived and what non-neural functions they are associated with, across different stages of 26 cancer types. Several novel discoveries are made, including i) the expressions of certain neural genes can predict the prognosis of a cancer patient; ii) cancer metastasis tends to involve specific neural functions; iii) cancers of low survival rates involve more neural interactions than those with high survival rates; iv) more malignant cancers involve more complex neural functions; and v) neural functions are probably induced to alleviate stresses and help the associated cancer cells to survive. A database, called NGC, is developed for organizing such derived neural functions and associations, along with gene expressions and functional annotations collected from public databases, aiming to provide an integrated and publicly available information resource to enable cancer researchers to take full advantage of the relevant information in their research, facilitated by tools provided by NGC.
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Gastric cancer has two distinct subtypes: the diffuse (DGC) and the intestinal (IGC) subtypes. Morphologically, the former each consists of numerous scattered tiny tumors while the latter each has one or a few solid biomasses. The former tends to be more aggressive and takes place in younger patients than the latter. While these have long been documented, little is known about the underlying causes. Our hypothesis is that the level of sialic acid (SA) accumulation on the cancer cell surfaces is a key reason for the observed differences. Our transcriptomic data-based analyses provide evidence that (i) DGCs tend to deploy more SAs on cancer cell surfaces than IGCs; (ii) this gives rise to considerably stronger cell-cell electrostatic repulsion in DGCs due to the negative charge that each SA carries; and (iii) such repulsion drives stronger cell protrusion and metastasis. Similar observations as well as our transcriptomic data-based predictions hold for multiple other cancer types, namely breast, lung, prostate plus liver and thyroid cancers, each known to have diffuse-like vs. non-diffused subtypes as well as more aggressive behaviors like DGCs vs. IGCs. Hence, we speculate that the discovery presented here applies not only to gastric cancer but multiple and even potentially all cancer types having diffuse-like and non-diffused subtypes.
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Brain metastasis of a cancer is a malignant disease with high mortality, but the cause and the molecular mechanism remain largely unknown. Using the samples of primary tumors of 22 cancer types in the TCGA database, we have performed a computational study of their transcriptomic data to investigate the drivers of brain metastases at the basic physics and chemistry level. Our main discoveries are: (i) the physical characteristics, namely electric charge, molecular weight, and the hydrophobicity of the extracellular structures of the expressed transmembrane proteins largely affect a primary cancer cell's ability to cross the blood-brain barrier; and (ii) brain metastasis may require specific functions provided by the activated enzymes in the metastasizing primary cancer cells for survival in the brain micro-environment. Both predictions are supported by published experimental studies. Based on these findings, we have built a classifier to predict if a given primary cancer may have brain metastasis, achieving the accuracy level at AUC = 0.92 on large test sets.
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Oxidative stress is known to be involved in and possibly a key driver of the development of numerous chronic diseases, including cancer. It is highly desired to have a capability to reliably estimate the level of intracellular oxidative stress as it can help to identify functional changes and disease phenotypes associated with such a stress, but the problem proves to be very challenging. We present a novel computational model for quantitatively estimating the level of oxidative stress in tissues and cells based on their transcriptomic data. The model consists of (i) three sets of marker genes found to be associated with the production of oxidizing molecules, the activated antioxidation programs and the intracellular stress attributed to oxidation, respectively; (ii) three polynomial functions defined over the expression levels of the three gene sets are developed aimed to capture the total oxidizing power, the activated antioxidation capacity and the oxidative stress level, respectively, with their detailed parameters estimated by solving an optimization problem and (iii) the optimization problem is so formulated to capture the relevant known insights such as the oxidative stress level generally goes up from normal to chronic diseases and then to cancer tissues. Systematic assessments on independent datasets indicate that the trained predictor is highly reliable and numerous insights are made based on its application results to samples in the TCGA, GTEx and GEO databases.
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Neoplasias , Estrés Oxidativo , Algoritmos , Humanos , Neoplasias/genética , Oxidación-ReducciónRESUMEN
By integrating network pharmacology and animal experiments, we studied the pharmacodynamic mechanism of the Tibetan medicine Liurui Capsules in the treatment of experimental autoimmune uveitis(EAU). The active ingredients and targets of Liurui Capsules were searched against the Encyclopedia of Traditional Chinese Medicine(ETCM), Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine(BATMAN-TCM), and relevant literatures. The EAU-related targets were obtained from Gene Expression Omnibus(GEO), GeneCards, Online Mendelian Inheritance in Man(OMIM), and Therapeutic Target Database(TTD). The common targets shared by Liurui Capsules and EAU were identified, and the protein-protein interaction(PPI) network was established via STRING. Gene Ontology(GO) annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were conducted via g: Profiler. The rat model of EAU was induced by interphotoreceptor retinoid-binding protein(IRBP) and treated with Liurui Capsules. The inflammatory response of anterior segment and the pathological morphology of retina were observed. The mRNA and protein levels of delta-like ligand 4(DLL4), Notch1, interleukin-17(IL-17), and tumor necrosis factor-alpha(TNF-α) were determined by real-time quantitative PCR(q-PCR) and Western blot, respectively. The network pharmacology analysis predicted 51 common targets of Liurui Capsules and EAU, which were mainly involved in IL-17, TNF, and nuclear factor-kappa B(NF-κB) signaling pathways, as well as liposome receptors and other biological processes. Compared with the control group, the modeling of EAU caused inflammatory changes in the anterior segment and retina and up-regulated mRNA and protein levels of DLL4, Notch1, IL-17, and TNF-α in ocular tissue. Compared with the model group, Liurui Capsules reduced the inflammatory reaction of anterior segment and retina and down-regulated the mRNA and protein levels of DLL4, Notch1, IL-17, and TNF-α. Liurui Capsules can down-regulate the expression of the proteins involved in DLL4/Notch1/IL-17 signaling pathway in ocular tissue and alleviate the ocular inflammation, which may be one of the mechanisms of Liurui Capsules in the treatment of EAU.
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Experimentación Animal , Medicamentos Herbarios Chinos , Uveítis , Ratas , Animales , Interleucina-17/efectos adversos , Interleucina-17/metabolismo , Factor de Necrosis Tumoral alfa , Medicina Tradicional Tibetana , Cápsulas , Farmacología en Red , Uveítis/tratamiento farmacológico , Uveítis/genética , Inflamación , Reacción en Cadena en Tiempo Real de la Polimerasa , ARN Mensajero/metabolismo , Medicamentos Herbarios Chinos/efectos adversos , Simulación del Acoplamiento MolecularRESUMEN
Data from the SEER reports reveal that the occurrence rate of a cancer type generally follows a unimodal distribution over age, peaking at an age that is cancer-type specific and ranges from 30+ through 70+. Previous studies attribute such bell-shaped distributions to the reduced proliferative potential in senior years but fail to explain why some cancers have their occurrence peak at 30+ or 40+. We present a computational model to offer a new explanation to such distributions. The model uses two factors to explain the observed age-dependent cancer occurrence rates: cancer risk of an organ and the availability level of the growth signals in circulation needed by a cancer type, with the former increasing and the latter decreasing with age. Regression analyses were conducted of known occurrence rates against such factors for triple negative breast cancer, testicular cancer and cervical cancer; and all achieved highly tight fitting results, which were also consistent with clinical, gene-expression and cancer-drug data. These reveal a fundamentally important relationship: while cancer is driven by endogenous stressors, it requires sufficient levels of exogenous growth signals to happen, hence suggesting the realistic possibility for treating cancer via cleaning out the growth signals in circulation needed by a cancer.
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Bases de Datos Factuales , Modelos Biológicos , Neoplasias Testiculares , Neoplasias de la Mama Triple Negativas , Neoplasias del Cuello Uterino , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias Testiculares/epidemiología , Neoplasias Testiculares/metabolismo , Neoplasias de la Mama Triple Negativas/epidemiología , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias del Cuello Uterino/epidemiología , Neoplasias del Cuello Uterino/metabolismoRESUMEN
Although social support is an indispensable resource for coping with illness, the connections among the structural properties of one's support network, received social support from offline and online network members, and well-being are not well understood. This study aims to extend the model of structural-to-functional support by distinguishing offline from online support networks and identifying different pathways through which these two networks contribute to patients' emotional well-being. Using data from 386 cancer patients, the results revealed that offline and online support networks were associated with patients' emotional well-being via different types of received support. Specifically, offline support network size was negatively associated with their emotional well-being via informational support received offline. Online support network size was positively associated with their emotional well-being via emotional support received online.
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Neoplasias , Apoyo Social , Adaptación Psicológica , Emociones , Humanos , Red SocialRESUMEN
Cisplatin is widely used in the chemoradiotherapy (CRT) of cervical cancers. However, despite the severe systemic side effects, the therapeutic efficacy of cisplatin is often compromised by the development of drug resistance, which is closely related to the elevated intracellular thiol-containing species (especially glutathione (GSH)) and the adenosine triphosphate (ATP)-dependent glutathione S-conjugate pumps. The construction of a safe and redox-sensitive nano-sensitizer with high disulfide density and high Pt(IV) prodrug loading capacity (up to 16.50% Pt and even higher), as described herein, is a promising way to overcome the cisplatin resistance and enhance the CRT efficacy. The optimized nanoparticles (NPs) (referred to as SSCV5) with moderate Pt loading (7.62% Pt) and median size (c.a. 40 nm) was screened out and used for further biological evaluation. Compared with free cisplatin, more drugs could be transported and released inside the cisplatin resistant cells (Hela-CDDP) by SSCV5 NPs. With the synergistic effect of GSH scavenging and mitochondrial damage, SSCV5 NPs can easily reverse the cisplatin resistance. Moreover, the higher nucleus DNA binding Pt content of SSCV5 NPs not only caused the DNA damage and apoptosis of Hela-CDDP cells but also sensitized these cells to X-Ray radiation. The in vivo safety and efficacy results showed that SSCV5 NPs effectively accumulated inside tumor and inhibited the growth of cisplatin resistant xenograft models while alleviating the serious side effect associated with cisplatin (the maximum tolerated cisplatin equivalent of single injection is higher than 20 mg/kg body weight). The intervention of exogenous radiation further improved the anticancer efficacy of SSCV5 NPs and caused the shrinkage of tumor volume, thus making this safe and facile nano-sensitizer a promising route for the neoadjuvant CRT of cervical cancers.
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Antineoplásicos , Nanopartículas , Profármacos , Neoplasias del Cuello Uterino , Línea Celular Tumoral , Quimioradioterapia , Cisplatino , Femenino , Humanos , Platino (Metal) , Neoplasias del Cuello Uterino/tratamiento farmacológicoRESUMEN
BACKGROUND: To investigate the correlation between plasma D-dimer level and severity and prognosis of patients admitted to the emergency department with trauma. METHODS: A total of 168 trauma patients admitted to the department of emergency surgery of Shengzhou People's Hospital were included in this study. The general information was collected, and the plasma D-dimer level was measured within 24 hours after admission. Patients were divided into the mild traumatic group (ISS ≤ 16 points), the moderate traumatic group (16 < ISS ≤ 25 points), and the severe traumatic group (ISS > 25 points) according to the Injury Severity Score (ISS) evaluation. According to the results from a 28-day follow-up, plasma D-dimer levels were compared between the survival group and the death group. The correlation between plasma D-dimer levels and severity of trauma patients admitted to the emergency department (according to the ISS) was analyzed. The receiver operating characteristic (ROC) curve evaluated the predictive value of plasma D-dimer levels for prognosis in patients admitted to the emergency department with trauma. RESULTS: Plasma D-dimer levels successively increased from the mild traumatic group (2.51 ± 0.46 mg/L), the moderate traumatic group (4.09 ± 1.00 mg/L) to the severe traumatic group (6.58 ± 1.14 mg/L) (F = 0.659, p < 0.05). Plasma D-dimer levels were significantly and positively correlated with ISSs (r = 0.720, p < 0.001). The plasma D-dimer level in the survival group (3.72 ± 1.26 mg/L) was significantly lower than that in the death group (5.19 ± 0.87 mg/L) (t = 6.251, p < 0.001). According to the Youden index, the optimal cutoff value of plasma D-dimer was 4.00 mg/L, the AUC was 0.849, the standard error was 0.034, the 95% CI was 0.783 - 0.915, the sensitivity was 0.938, and the specificity was 0.603. CONCLUSIONS: Plasma D-dimer levels were positively correlated with the severity of patients with trauma admitted to the department of emergency surgery and can predict poor prognosis.
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Productos de Degradación de Fibrina-Fibrinógeno/análisis , Heridas y Lesiones , Adulto , Servicio de Urgencia en Hospital , Humanos , Puntaje de Gravedad del Traumatismo , Persona de Mediana Edad , Pronóstico , Curva ROC , Estudios Retrospectivos , Heridas y Lesiones/sangre , Heridas y Lesiones/diagnóstico , Heridas y Lesiones/epidemiología , Heridas y Lesiones/fisiopatología , Adulto JovenRESUMEN
Skin itching is a subjective sensation that causes the desire to scratch. It is one of the most common clinical symptoms at department of dermatology, even the only complaint of dermatological patients, which seriously affects the quality life of patients. Therefore, based on the software of traditional Chinese medicine inheritance auxiliary platform, association rules and complex system entropy clustering were adopted to collect and analyze Zhang Bing's prescriptions for skin itching, and get the drug use frequency and the relationship between drugs. Based on that, we could conclude the experience for skin itching. A total of 147 prescriptions were collected, 20 drugs with a frequency of 34 or more and 20 high-frequency drug combinations were analyzed, and 14 core combinations and 7 new prescriptions were excavated. The high-frequency drugs included Kochiae Fructus, Dictamni Cortex, Mori Cortex. The high-frequency drug combinations included "Kochiae Fructus-Dictamni Cortex" "Angelicae Dahuricae Radix-Chuanxiong Rhizoma" "Paeoniae Radix Rubra-Paeoniae Radix Alba", and the core combinations included "Schizonepetae Herba-Saposhnikoviae Radix-Cinnamomi Ramulus" "Arctii Fructus-Cicadae Periostracum-Houttuyniae Herba" "Ghrysanthemi Indici Flos-Kochiae Fructus-Dictamni Cortex", and new formulations include "Schizonepetae Herba, Saposhnikoviae Radix, Cinnamomi Ramulus, Clematidis Radix et Rhizoma, Tribuli Fructus, Dictamni Cortex", "Phellodendri Chinensis Coritex, Lonicerae Japonicae Flos, Atractylodis Rhizoma, Ghrysanthemi Indici Flos, Kochiae Fructus, Dictamni Cortex" "Arctii Fructus, Cicadae Periostracum, Houttuyniae Herba, Trichosanthis Fructus". The result of this research shows that Professor Zhang Bing's experience in the treatment of skin itching is mainly to dispelling wind and arresting itching, clearing heat and drying dampness.
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Minería de Datos , Medicamentos Herbarios Chinos/uso terapéutico , Medicina Tradicional China , Prurito/tratamiento farmacológico , Combinación de Medicamentos , Humanos , Programas InformáticosRESUMEN
Aeration by airflow technology is a reliable method to accelerate waste biodegradation and stabilization and hence shorten the aftercare period of a landfill. To simulate hydro-biochemical behaviors in this type of landfills, this study develops a model coupling multi-phase flow, multi-component transport and aerobic-anaerobic biodegradation using a computational fluid dynamics (CFD) method. The uniqueness of the model is that it can well describe the evolution of aerobic zone, anaerobic zone, and temperature during aeration and evaluate aeration efficiency considering aerobic and anaerobic biodegradation processes. After being verified using existing in situ and laboratory test results, the model is then employed to reveal the bio-stable zone development, aerobic biochemical reactions around vertical well (VW), and anaerobic reactions away from VW. With an increase in the initial organic matter content (0.1 to 0.4), the bio-stable zone expands at a decreasing speed but with all the horizontal ranges larger than 17 m after an intermittent aeration for 1000 days. When waste intrinsic permeability is equal or greater than 10-11 m2, aeration using a low pressure between 4 and 8 kPa is appropriate. The aeration efficiency would be underestimated if anaerobic biodegradation is neglected because products of anaerobic biodegradation would be oxidized more easily. A horizontal spacing of 17 m is suggested for aeration VWs with a vertical spacing of 10 m for screens. Since a lower aeration frequency can give greater aeration efficiency, a 20-day aeration/20-day leachate recirculation scenario is recommended considering the maximum temperature over a reasonable range. For wet landfills with low temperature, the proportion of aeration can be increased to 0.67 (20-day aeration/10-day leachate recirculation) or an even higher value.
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Reactores Biológicos , Eliminación de Residuos/métodos , Instalaciones de Eliminación de Residuos/instrumentación , Aerobiosis , Biodegradación AmbientalRESUMEN
Xanthii Fructus is a traditional Chinese medicine for the treatment of sinusitis and headache,rich in medicinal materials and is widely used for more than 1 800 years. Modern pharmacological studies have showed that Xanthii Fructus has anti-inflammatory,analgesic,anti-tumor,anti-bacterial,hypoglycemic,anti-allergic,immunomodulatory and other pharmacological effects,which can be commonly used in the treatment of diseases relating to immune abnormalities,such as rheumatoid arthritis,acute and chronic rhinitis,allergic rhinitis,and skin diseases,with a high medicinal value. Toxicological studies have shown that Xanthii Fructus poisoning can cause substantial damage to organs,such as the liver,kidney,and gastrointestinal tract,especially to liver. Because of the coexisting of its efficacy and toxicity,Xanthii Fructus often leads to a series of safety problems in the clinical application process. This study attempts to summarize its characteristics of adverse reactions,analyze the root cause of the toxicity of Xanthii Fructus from such aspects as processing,dose,course of treatment and eating by mistake,discuss the substance of its efficacy/toxicity from chemical compositions,and put forward exploratory thinking about how to promote its clinical rational application from the aspects such as strict processing,reasonable compatibility,medication information,contraindication,strict control of the dose,and course of treatment,so as to promote the safe and reasonable application of Xanthii Fructus.
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Medicamentos Herbarios Chinos/efectos adversos , Frutas/toxicidad , Xanthium/toxicidad , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Medicina Tradicional ChinaRESUMEN
The most commonly used method of operating landfills more sustainably is to promote rapid biodegradation and stabilization of municipal solid waste (MSW) by leachate recirculation. The present study is an application of computational fluid dynamics (CFD) to the 3D modeling of leachate recirculation in bioreactor landfills using vertical wells. The objective is to model and investigate the hydrodynamic and biochemical behavior of MSW subject to leachate recirculation. The results indicate that the maximum recirculated leachate volume can be reached when vertical wells are set at the upper middle part of a landfill (H W/H T = 0.4), and increasing the screen length can be more helpful in enlarging the influence radius than increasing the well length (an increase in H S/H W from 0.4 to 0.6 results in an increase in influence radius from 6.5 to 7.7 m). The time to reach steady state of leachate recirculation decreases with the increase in pressure head; however, the time for leachate to drain away increases with the increase in pressure head. It also showed that methanogenic biomass inoculum of 1.0 kg/m3 can accelerate the volatile fatty acid depletion and increase the peak depletion rate to 2.7 × 10-6 kg/m3/s. The degradation-induced void change parameter exerts an influence on the processes of MSW biodegradation because a smaller parameter value results in a greater increase in void space.
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Reactores Biológicos , Modelos Teóricos , Eliminación de Residuos/métodos , Residuos Sólidos/análisis , Instalaciones de Eliminación de Residuos , Contaminantes Químicos del Agua/análisis , Biodegradación AmbientalRESUMEN
Sixty SD male rats were randomly divided into normal group, model group, benzbromarone group(20 mgâ¢kg⻹â¢d⻹), chicory extract high dose, middle dose and low dose groups (5, 7.5, 10 gâ¢kg⻹â¢d⻹). The rats in normal group were given with water, and the rats in other groups were given with 10% fructose solution to establish hyperuricemia models. All the rats were sacrificed on the 42th day. Then their serum uric acid(SUA), serum creatinine(CRE), urea nitrogen(BUN) and urinary uric acid(UUA) levels were detected to calculate the clearance rate of uric acid in kidney(CUA). Meanwhile, the protein and gene expression levels of renal glucose transporter family member 9(Glut9) were detected by immunohistochemical and Real-time quantitative reverse transcription-polymerase chain reaction(RT-qPCR) methods. The effects of Chinese herb chicory extract on expression of renal Glut9 and decreasing uric acid were explored in this study, and the results showed that chicory extract could reduce SUA level in rats with hyperuricemia, increase renal CUA, decrease the protein expression of renal Glut9, inhibit uric acid re-absorption in kidney, and thus promote renal uric acid excretion.
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Cichorium intybus/química , Medicamentos Herbarios Chinos/farmacología , Hiperuricemia/tratamiento farmacológico , Proteínas de Transporte de Monosacáridos/metabolismo , Animales , Benzbromarona , Riñón/efectos de los fármacos , Masculino , Extractos Vegetales/farmacología , Ratas , Ratas Sprague-Dawley , Ácido Úrico/sangreRESUMEN
The aim of the current investigation was to evaluate the anti-fibrosis potential of human umbilical cord mesenchymal stem cells (hUC-MSCs) and further to explore some of its underlying mechanisms. Hepatic fibrosis mice model was induced by CCl4. Liver function parameters in serum and fibrosis-associated markers in tissues were detected. Moreover, SB-431542, an anti-TGFß-1 receptor inhibitor, was employed in vitro to reveal the underlying mechanism of TGFß-1/Smad pathway on hUC-MSCs against liver fibrosis. In the present study, we illustrated that hUC-MSCs could differentiate into osteogenic, adipogenic, and cartilage. Liver fibrosis was attenuated with hUC-MSCs treatment, determined by reductions of AST, ALT. and fibrosis area, along with some critical parameters including TGFß-1, α-SMA, and TIMP-1. However, TGFß-1 receptor antagonist SB-431542 reduced the paracrine TGFß-1 expression of hUC-MSCs and blunted the activation of downstream target genes. Furthermore, the restrained hUC-MSCs proliferation and migration induced by SB-431542 could be reversed by si-TGFß-1. These results demonstrated that TGFß-1 receptor inhibitor improved the repair potential of hUC-MSCs against hepatic injury through TGFß-1/Smad pathway, which contributed to improving the therapeutic efficiency of liver fibrosis.
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Benzamidas/farmacología , Dioxoles/farmacología , Cirrosis Hepática/terapia , Trasplante de Células Madre Mesenquimatosas/métodos , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Cordón Umbilical/citología , Animales , Tetracloruro de Carbono/toxicidad , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Terapia Combinada , Modelos Animales de Enfermedad , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Cirrosis Hepática/inducido químicamente , Cirrosis Hepática/metabolismo , Ratones , Transducción de Señal/efectos de los fármacos , Resultado del TratamientoRESUMEN
Previous literature has suggested that examining Twitter messages can be productive for studying how the public shares and spreads health information on social media. Preexposure prophylaxis (PrEP) is a promising approach to HIV prevention, yet there are many issues that may influence its effective implementation. This study examined social representations of PrEP on Twitter. One thousand four hundred and thirty-five Tweets were collected and 774 English Tweets were content-analyzed to explore propagation of various issues around daily oral PrEP, as well as characteristics of the sources of those Tweets. We also examined how Twitter message content influenced information propagation. Our findings revealed that PrEP-related information on Twitter covered a wide range of issues, and individual users constituted the majority of the Tweet creators among all the sources, including news media, nonprofit and academic groups, and commercial entities. Using Poisson regression, we also found that a Tweet's affective tone was a significant predictor of message propagation frequency. Implications for health practitioners are discussed.