RESUMEN
Red radish (Raphanus L.) pickles are popular appetizers or spices in Asian-style cuisine. However, tons of radish brines are generated as wastes from industrial radish pickle production. In this study, we evaluated the dynamic changes in colour properties, phenolics, anthocyanin profiles, phenolic acid composition, flavonoids, and antioxidant properties in radish brines during lactic acid fermentation. The results showed that five flavonoids detected were four anthocyanins and one kaempferol derivative, including pelargonidin-3-digluoside-5-glucoside derivatives acylated with p-coumaric acid, ferulic acid, p-coumaric and manolic acids, or ferulic and malonic acids. Amounts ranged from 15.5-19.3 µg/mL in total monomeric anthocyanins, and kaempferol-3,7-diglycoside (15-30 µg/mL). 4-Hydroxy-benzoic, gentisic, vanillic, syringic, p-coumaric, ferulic, sinapic and salicylic acids were detected in amounts that varied from 70.2-92.2 µg/mL, whereas the total phenolic content was 206-220 µg/mL. The change in colour of the brine was associated with the accumulation of lactic acid and anthocyanins. The ORAC and Fe2+ chelation capacity of radish brines generally decreased, whereas the reducing power measured as FRAP values was increased during the fermentation from day 5 to day 14. This study provided information on the phytochemicals and the antioxidative activities of red radish fermentation waste that might lead to further utilization as nutraceuticals or natural colorants.
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Antioxidantes/química , Fermentación , Ácido Láctico/química , Fitoquímicos/química , Raphanus/química , Sales (Química)/química , Antocianinas , Antioxidantes/farmacología , Flavonoides , Concentración de Iones de Hidrógeno , Hidroxibenzoatos , Fenoles , Fitoquímicos/farmacología , Pigmentos Biológicos/química , Sales (Química)/farmacologíaRESUMEN
To evaluate in vitro release and transdermal behaviors of Huoxue Zhitong gel, modified Franz diffusion cell methods was applied to investigate in vitro transdermal absorption of Huoxue Zhitong gel and the content of paeonolan in receptor fluid composed of PEG400%-95% ethanol-water (l:3:6)were determined by HPLC. The results were processed and different equations were fitted. The release law were in accordance with Weibull equation and the fitting equation was In[-1/(1 - Q)] = -0.790 51nt - 1.7012 (r = 0.9809). In 8 hours, cumulative release of paeonol was 85. 18% and the release rate was 2.827 µg . cm-2 h-1. Transdermal actions were consistent with zero-level model fit and the fitting equation was Q(t) = 1.7579t + 0. 7213 (r = 0.9991). In 8 hours, cumulative transdermal rate and transmission rate of paeonol was 54. 85%, 1. 820 µg . cm-2 h-1. So the Huoxue Zhitong gel had a good release and transdermal properties.
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Acetofenonas/farmacocinética , Medicamentos Herbarios Chinos/farmacocinética , Absorción Cutánea , Acetofenonas/administración & dosificación , Administración Cutánea , Animales , Cromatografía Líquida de Alta Presión , Medicamentos Herbarios Chinos/administración & dosificación , Geles , RatonesRESUMEN
Long-term consumption of Western-style diet (WSD) can lead to metabolic disorders and dysbiosis of gut microbiota, presenting a critical risk factor for various chronic conditions such as fatty liver disease. In the present study, we investigated the beneficial role of co-fermented whole grain quinoa and black barley with Lactobacillus kisonensis on rats fed a WSD. Male Sprague-Dawley (SD) rats, aged six weeks and weighing 180 ± 10 g, were randomly assigned to one of three groups: the normal control group (NC, n = 7), the WSD group (HF, n = 7), and the WSD supplemented with a co-fermented whole grain quinoa with black barley (FQB) intervention group (HFF, n = 7). The findings indicated that FQB was effective in suppressing body weight gain, mitigating hepatic steatosis, reducing perirenal fat accumulation, and ameliorating pathological damage in the livers and testicular tissues of rats. Additionally, FQB intervention led to decreased levels of serum uric acid (UA), aspartate aminotransferase (AST), and alanine aminotransferase (ALT). These advantageous effects can be ascribed to the regulation of FQB on gut microbiota dysbiosis, which includes the restoration of intestinal flora diversity, reduction of the F/B ratio, and promotion of probiotics abundance, such as Akkermansia and [Ruminococcus] at the genus level. The study employed the UPLC-Q-TOF-MSE technique to analyze metabolites in fecal and hepatic samples. The findings revealed that FQB intervention led to a regression in the levels of specific metabolites in feces, including oxoadipic acid and 20a, 22b-dihydroxycholesterol, as well as in the liver, such as pyridoxamine, xanthine and xanthosine. The transcriptome sequencing of liver tissues revealed that FQB intervention modulated the mRNA expression of specific genes, including Cxcl12, Cidea, and Gck, known for their roles in anti-inflammatory and anti-insulin resistance mechanisms in the context of WSD. Our findings indicate that co-fermented whole-grain quinoa with black barley has the potential to alleviate metabolic disorders and chronic inflammation resulting from the consumption of WSD.
Asunto(s)
Chenopodium quinoa , Dieta Occidental , Fermentación , Microbioma Gastrointestinal , Hordeum , Lactobacillus , Ratas Sprague-Dawley , Animales , Hordeum/química , Masculino , Lactobacillus/metabolismo , Chenopodium quinoa/química , Ratas , Hígado/metabolismo , Disbiosis , Metabolómica , Alimentos Fermentados , MultiómicaRESUMEN
OBJECTIVE: To establish a quantitative method to detect circulating tumor cells (CTC) in patients with small cell lung cancer, and analyze its sensitivity and stability. METHODS: A specific primer and probe for prepro-gastrin-releasing peptide (preproGRP) was designed and a quantitative RT-PCR method was established to detect preproGRP mRNA. Cell incorporation method was used to evaluate the sensitivity. Magnetic cell sorting (MACS) was used to isolate and purify CTC from peripheral blood, and the MACS in combination with morphological diagnosis were used for cell counting. RESULTS: The isolation rate of CTC by MACS was 30% and the lower detection limit was 5 cells per ml blood. The sensitivity of quantitative RT-PCR in detection of preproGRP mRNA in CTC was 0.64 cells per reaction, and the lower detection limit was 50 cells per ml blood, which was lower than that of MACS. However, the cell numbers calculated by Ct value was in greater accordance (about 80%) with actual cell numbers than that obtained by MACS. CONCLUSIONS: PreproGRP quantitative RT-PCR and MACS have both advantages and disadvantages in detecting CTC of SCLC patients. MACS has a higher sensitivity, and is more favorable when CTC count is below 50 per ml blood. Meanwhile, preproGRP mRNA quantitative RT-PCR is more reliable in calculating actual cell numbers.
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Neoplasias Pulmonares/patología , Células Neoplásicas Circulantes , Péptidos/metabolismo , Precursores de Proteínas/metabolismo , Carcinoma Pulmonar de Células Pequeñas/patología , Humanos , Separación Inmunomagnética , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/metabolismo , Péptidos/genética , Precursores de Proteínas/genética , ARN Mensajero/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Carcinoma Pulmonar de Células Pequeñas/sangre , Carcinoma Pulmonar de Células Pequeñas/metabolismoRESUMEN
To evaluate in vitro release and transdermal behaviors of Zhitong cataplasm, modified Franz diffusion cell method was applied to investigate in vitro transdermal absorption of Zhitong cataplasm and the content of tetrahydropalmatine was determined by HPLC. In 24 hours, accumulative release rate of tetrahydropalmatine was 81. 9%, transmission rate was 2.26 microg x cm(-2) x h(-1). In 48 hours, accumulative transdermal rate and transmission rate of tetrahydropalmatine were 20.31%, 0.22 pg x cm(-2) x h(-1). So Zhitong cataplasm had a good release and transdermal properties and transdermal actions were consistent with zero-order kinetics process.
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Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacocinética , Administración Cutánea , Animales , Alcaloides de Berberina/administración & dosificación , Alcaloides de Berberina/química , Alcaloides de Berberina/farmacocinética , Medicamentos Herbarios Chinos/administración & dosificación , Masculino , Ratones , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Extractos Vegetales/farmacocinética , Piel/metabolismo , Absorción CutáneaRESUMEN
Increasing evidence demonstrates that melatonin has an anti-inflammatory effect. Nevertheless, the molecular mechanisms remain obscure. In this study, we investigated the effect of melatonin on toll-like receptor 4 (TLR4)-mediated molecule myeloid differentiation factor 88 (MyD88)-dependent and TRIF-dependent signaling pathways in lipopolysaccharide (LPS)-stimulated macrophages. RAW264.7 cells were incubated with LPS (2.0 µg/mL) in the absence or presence of melatonin (10, 100, 1000 µm). As expected, melatonin inhibited TLR4-mediated tumor necrosis factor alpha (TNF-α), interleukin (IL)-1ß, IL-6, IL-8, and IL-10 in LPS-stimulated macrophages. In addition, melatonin significantly attenuated LPS-induced upregulation of cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) in macrophages. Further analysis showed that melatonin inhibited the expression of MyD88 in LPS-stimulated macrophages. Although it had no effect on TLR4-mediated phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular regulated protein kinase (ERK), melatonin significantly attenuated the activation of nuclear factor kappa B (NF-κB) in LPS-stimulated macrophages. In addition, melatonin inhibited TLR4-mediated Akt phosphorylation in LPS-stimulated macrophages. Moreover, melatonin significantly attenuated the elevation of interferon (IFN)-regulated factor-3 (IRF3), which was involved in TLR4-mediated TRIF-dependent signaling pathway, in LPS-stimulated macrophages. Correspondingly, melatonin significantly alleviated LPS-induced IFN-ß in macrophages. In conclusion, melatonin modulates TLR4-mediated inflammatory genes through MyD88-dependent and TRIF-dependent signaling pathways.
Asunto(s)
Proteínas Adaptadoras del Transporte Vesicular/metabolismo , Antiinflamatorios/farmacología , Mediadores de Inflamación/metabolismo , Inflamación/prevención & control , Lipopolisacáridos/farmacología , Macrófagos/efectos de los fármacos , Melatonina/farmacología , Factor 88 de Diferenciación Mieloide/metabolismo , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/efectos de los fármacos , Proteínas Adaptadoras del Transporte Vesicular/genética , Animales , Línea Celular , Ciclooxigenasa 2/genética , Ciclooxigenasa 2/metabolismo , Citocinas/genética , Citocinas/metabolismo , Relación Dosis-Respuesta a Droga , Activación Enzimática , Regulación de la Expresión Génica , Inflamación/genética , Inflamación/inmunología , Inflamación/metabolismo , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Factor 88 de Diferenciación Mieloide/genética , FN-kappa B/metabolismo , Óxido Nítrico Sintasa de Tipo II/genética , Óxido Nítrico Sintasa de Tipo II/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Mensajero/metabolismo , Factores de Tiempo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismoRESUMEN
An investigation was designed and conducted to detect pharmacokinetic differences between paeoniflorin (Pae) microemulsion and Pae saline. Pae microemulsion (25, 50,100 mg x kg(-1)) was administered to three groups of rats with adjuvant arthritis (AA) while Pae (25, 50,100 mg x kg(-1)) was given to another three groups of rats both for ten days. A HPLC assay was developed to determine the plasma concentrations of Pae. The plasma concentrations of Pae groups (25, 50 mg x kg(-1)) were undetectable. Furthermore, compared with pharmacokinetic parameters of Pae group (100 mg x kg(-1)), maximum concentration (C(max)), the area under the plasma concentration-time curve (AUC(0-t)), and mean retention time MRT(0-infinity))(h) of Pae microemulsion (100 mg x kg(-1)) increased apparently, while volume of distribution (Vd) and clearance rate (CL/F) decreased. These results indicate that a microemulsion significantly improves the absorption of Pae in AA rats.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacocinética , Artritis Experimental/metabolismo , Benzoatos/farmacocinética , Hidrocarburos Aromáticos con Puentes/farmacocinética , Glucósidos/farmacocinética , Animales , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/uso terapéutico , Área Bajo la Curva , Artritis Experimental/tratamiento farmacológico , Artritis Experimental/patología , Benzoatos/administración & dosificación , Benzoatos/uso terapéutico , Disponibilidad Biológica , Hidrocarburos Aromáticos con Puentes/administración & dosificación , Hidrocarburos Aromáticos con Puentes/uso terapéutico , Calibración , Cromatografía Líquida de Alta Presión , Edema/etiología , Edema/patología , Emulsiones , Pie/patología , Adyuvante de Freund , Glucósidos/administración & dosificación , Glucósidos/uso terapéutico , Semivida , Indicadores y Reactivos , Masculino , Monoterpenos , Paeonia/química , Raíces de Plantas/química , Ratas , Ratas Sprague-DawleyRESUMEN
In this study, we report a one-pot synthesis and enzyme-responsiveness of polyethylene glycol (PEG) and glutamic acid (Glu)-based amphiphilic doxorubicin (DOX) prodrug nanomicelles for cancer therapeutics. The nanomicelles were accomplished by esterification and amidation reactions. The nuclear magnetic resonance (NMR) and Fourier transform infrared (FTIR) data confirmed the structure of nanomicelles. The DOX-loaded nanomicelles showed a DLS-measured average size of 107 nm and excellent stability in phosphate-buffered saline (PBS) for 7 days. The drug loading and cumulative release rates were measured by ultraviolet-visible (UV-vis) spectrophotometry at 481 nm. The cumulative release rate could reach 100% in an enzyme-rich environment. Further, the therapeutic efficiency of nanomicelles to cancer cells was determined by cell viability and cellular uptake and distribution using HeLa cells. The cell viability study showed that the DOX-loaded nanomicelles could effectively inhibit the HeLa cell proliferation. The cellular uptake study confirmed that the nanomicelles could be effectively ingested by HeLa cells and distributed into cell nuclei. Based on the collective experimental data, this study demonstrated that the synthesized nanomicellar prodrug of DOX is a potential candidate for cancer therapeutics.
RESUMEN
A long-term high-fat (HF) diet can cause metabolic disorders, which might induce visceral obesity and ectopic triglyceride storage (e.g., hepatic steatosis), and increase hepatic oxidative stress. Oxidative stress plays a significant role in the development of complications associated with obesity. Fermented whole cereal foods exhibit healthy potential due to their unique phytochemical composition and the presence of probiotics. In the present study, the regular nutrients and phytochemicals of Lactobacillus-fermented black barley (Hordeum distichum L.) were analyzed. Further, the black barley fermentation broth (1 mL per 100 g BW per d, equivalent to 1 mL per kg BW of daily human intake) was administered orally to the rats fed on a high fat diet (HF). The anti-oxidative activity and hepatic metabolic profile of Lactobacillus-fermented black barley were investigated. The results showed that the fermentation processing significantly increased the contents of polyphenols (e.g., ferulic acid, etc.), flavonoids (e.g., flavone, etc.), vitamin B1 and B2, partial mineral elements (e.g., Ca, etc.), and thymine. Furthermore, compared to the HF-fed only rats, fermented black barley treatment significantly increased the activities of SOD (superoxide dismutase) and GSH-PX (glutathione peroxidase), and decreased the level of TBARS (thiobarbituric acid reactive substances) in serum, the levels of TG (triglyceride), TC (total cholesterol), NEFA (non-esterified fatty acid) in the liver, and the levels of TC, NEFA in the adipose tissue. This suggested the beneficial effects of fermented black barley on ameliorating oxidative stress and hepatic steatosis, which could be attributed to its regulatory role in the hepatic metabolism of glycerophospholipids, nicotinate and nicotinamide, glutathione, and nucleotide, and on the expression of genes related to oxidative stress (Heat shock protein 90 and reactive oxygen species modulator 1).
Asunto(s)
Hígado Graso/tratamiento farmacológico , Fermentación , Hordeum/metabolismo , Lactobacillus/metabolismo , Fitoquímicos/farmacología , Animales , Antioxidantes/farmacología , Dieta Alta en Grasa/efectos adversos , Hígado Graso/metabolismo , Flavonoides/metabolismo , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Hordeum/química , Hígado/metabolismo , Masculino , Obesidad/metabolismo , Estrés Oxidativo/efectos de los fármacos , Fitoquímicos/química , Ratas , Ratas Sprague-Dawley , Superóxido Dismutasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Triglicéridos/sangreRESUMEN
OBJECTIVE: To investigate the value of carcinoembryonic antigen (CEA) or cytokeratin 19 fragment (CYFRA21-1) as an assessment indicator of therapeutic efficacy in advanced non-small cell lung cancer (NSCLC) patients. METHODS: 228 cases of advanced NSCLC with chemotherapy were enrolled into this retrospective study. The serum CEA or CYFRA21-1 levels of all patients were above the cut-off limit before treatment. The relationship between changes of tumor markers (TMs) and imaging therapeutic efficacy or progression-free survival (PFS) was analyzed, and the value of TMs in therapeutic efficacy assessment was evaluated. RESULTS: According to RECIST criteria, partial response (PR) occurred in 40 cases, stable disease (SD) in 151 and PD (progressive disease) in 37. The cut-off values of the changes of TMs between pre- and post-treatment were determined according to the above mentioned criteria. The CEA down (D), stable (S), above (A) groups were 90, 49 and 66 cases, respectively. CYFRA21-1 down (D), stable (S), above (A) groups were 84, 26 and 37 cases, respectively. PR groups were 68.4% and 88.9% in CEA and cyfra21-1 down groups, respectively, 7.9% and 5.6% in the above groups, respectively. PD groups were 59.4% and 76.2% in CEA and CYFRA21-1 above groups, respectively. No PD cases were in the down groups. The changes of TMs in SD group were between them. Statistically significant correlations were observed between changes of TMs and imaging therapeutic efficacy (r(CEA) = 0.45, P = 0.00; r(CYFRA21-1) = 0.44, P = 0.00). PFS among different TMs groups were significantly different (all P < 0.05), which can be used to further distinguish the prognosis among SD subgroups. CONCLUSION: Changes of TMs can be used to predict the imaging therapeutic effect and PFS of the patients, and if the SD group is divided into subgroups according to different therapeutic efficacy and prognosis, it may help the patients to receive individualized treatment.
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Antígenos de Neoplasias/sangre , Antígeno Carcinoembrionario/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Queratina-19/sangre , Neoplasias Pulmonares/sangre , Anciano , Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Inducción de Remisión , Estudios RetrospectivosRESUMEN
MicroRNAs (miRNAs) have been identified as critical modulators of cell migration and invasion, which are the major causes of cancer progression including hepatocellular carcinoma (HCC). However, the accurate role of miR-515-5p in HCC is still uncertain. Here, we report that miR-515-5p expression is down-regulated in HCC tissues and cell lines, and associated with absence of capsule formation (p = 0.015)ï¹microvascular invasion(p = 0.003)ï¹and advantange TNM stage (II-III) (p = 0.014) in HCC patients. Overexpression of miR-515-5p inhibited migration and invasion of HCC cells in vitro and in vivo, while miR-515-5p knockdown has the inverse effect. Moreover, using miRNA databases and dual-luciferase report assay, we find miR-515-5p directly binds to the 3'-untranslated region (3'-UTR) of interleukin 6 (IL6). In addition, the regulatory association between miR-515-5p and the IL-6/Janus kinase (JNK)/signal transducer and activator of transcription-3 (STAT3) signaling pathway was explored. Furthermore, overexpression of miR-515-5p inhibited the activation of the JAK/STAT3 signaling pathway, which was rescued by overexpression of IL-6. The results of the current study indicate that miR-515-5p overexpression may serve an important role in inhibiting migration and invasion of HCC cells via suppression of IL-6/JAK/STAT3 signaling pathway activation. MiR-515-5p may serve as a potential therapeutic target for HCC.
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Carcinoma Hepatocelular/patología , Regulación Neoplásica de la Expresión Génica , Interleucina-6/metabolismo , Janus Quinasa 1/metabolismo , Neoplasias Hepáticas/patología , MicroARNs/genética , Factor de Transcripción STAT3/metabolismo , Animales , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Movimiento Celular , Proliferación Celular , Femenino , Humanos , Interleucina-6/genética , Janus Quinasa 1/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Ratones , Ratones Desnudos , Persona de Mediana Edad , Pronóstico , Factor de Transcripción STAT3/genética , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: Medicines for the treatment of 2019-novel coronavirus (2019-nCoV) infections are urgently needed. However, drug screening using live 2019-nCoV requires high-level biosafety facilities, which imposes an obstacle for those institutions without such facilities or 2019-nCoV. This study aims to repurpose the clinically approved drugs for the treatment of coronavirus disease 2019 (COVID-19) in a 2019-nCoV-related coronavirus model. METHODS: A 2019-nCoV-related pangolin coronavirus GX_P2V/pangolin/2017/Guangxi was described. Whether GX_P2V uses angiotensin-converting enzyme 2 (ACE2) as the cell receptor was investigated by using small interfering RNA (siRNA)-mediated silencing of ACE2. The pangolin coronavirus model was used to identify drug candidates for treating 2019-nCoV infection. Two libraries of 2406 clinically approved drugs were screened for their ability to inhibit cytopathic effects on Vero E6 cells by GX_P2V infection. The anti-viral activities and anti-viral mechanisms of potential drugs were further investigated. Viral yields of RNAs and infectious particles were quantified by quantitative real-time polymerase chain reaction (qRT-PCR) and plaque assay, respectively. RESULTS: The spike protein of coronavirus GX_P2V shares 92.2% amino acid identity with that of 2019-nCoV isolate Wuhan-hu-1, and uses ACE2 as the receptor for infection just like 2019-nCoV. Three drugs, including cepharanthine (CEP), selamectin, and mefloquine hydrochloride, exhibited complete inhibition of cytopathic effects in cell culture at 10 µmol/L. CEP demonstrated the most potent inhibition of GX_P2V infection, with a concentration for 50% of maximal effect [EC50] of 0.98 µmol/L. The viral RNA yield in cells treated with 10 µmol/L CEP was 15,393-fold lower than in cells without CEP treatment ([6.48â±â0.02]â×â10vs. 1.00â±â0.12, tâ=â150.38, Pâ<â0.001) at 72 h post-infection (p.i.). Plaque assays found no production of live viruses in media containing 10 µmol/L CEP at 48 h p.i. Furthermore, we found CEP had potent anti-viral activities against both viral entry (0.46â±â0.12, vs.1.00â±â0.37, tâ=â2.42, Pâ<â0.05) and viral replication ([6.18â±â0.95]â×â10vs. 1.00â±â0.43, tâ=â3.98, Pâ<â0.05). CONCLUSIONS: Our pangolin coronavirus GX_P2V is a workable model for 2019-nCoV research. CEP, selamectin, and mefloquine hydrochloride are potential drugs for treating 2019-nCoV infection. Our results strongly suggest that CEP is a wide-spectrum inhibitor of pan-betacoronavirus, and further study of CEP for treatment of 2019-nCoV infection is warranted.
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Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Neumonía Viral/tratamiento farmacológico , Betacoronavirus/genética , COVID-19 , Prueba de COVID-19 , Línea Celular , Técnicas de Laboratorio Clínico , Infecciones por Coronavirus/diagnóstico , Aprobación de Drogas , Humanos , Pandemias , Neumonía Viral/diagnóstico , ARN Interferente Pequeño/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , SARS-CoV-2 , Carga Viral , Tratamiento Farmacológico de COVID-19RESUMEN
BACKGROUND: Circular RNAs (circRNAs) play a critical regulatory role in cancer progression. However, the underlying mechanisms of circRNAs in hepatocellular carcinoma (HCC) metastasis remain mostly unknown. METHODS: Has_circ_0003998 (circ0003998) was identified by RNAs sequencing in HCC patients with /without portal vein tumor thrombus (PVTT) metastasis. The expression level of circ0003998 was further detected by in situ hybridization on tissues microarray (ISH-TMA) and qRT-PCR in 25 HCC patients with PVTT metastasis. Moreover, the 25 HCC patients with PVTT metastasis and 50 HCC patients without PVTT metastasis were recruited together to analyze the correlation between circ0003998 expression and HCC clinical characteristics. Transwell, migration and CCK8 assays, as well as nude mice model of lung or liver metastasis were used to evaluate the role of circ0003998 in epithelial to mesenchymal transition (EMT) in HCC. The regulatory mechanisms of circ0003998 in miR-143-3p and PCBP1 were determined by dual-luciferase reporter assay, nuclear-cytoplasmic fractionation, fluorescent in situ hybridization, RNA pull- down, microRNA sequence, western blot and RNA immunoprecipitation. RESULTS: Compared with adjacent normal liver tissues (ANL), circ0003998 expression was significantly upregulated in PVTT tissues and HCC tissues, and its expression correlates with the aggressive characteristics of HCC patients. Further assays suggested that circ0003998 promoted EMT of HCC both in vitro and in vivo. Mechanistically, our data indicated that circ0003998 may act as a ceRNA (competing endogenous RNA) of microRNA-143-3p to relieve the repressive effect on EMT-related stimulator, FOSL2; meanwhile, circ0003998 could bind with PCBP1-poly(rC) binding protein 1 (PCBP1) to increase the expression level of EMT-related genes, CD44v6. CONCLUSION: Circ0003998 promotes EMT of HCC by circ0003998/miR-143-3p/FOSL2 axis and circ0003998 /PCBP1/CD44v6 axis.
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Biomarcadores de Tumor/metabolismo , Carcinoma Hepatocelular/patología , Proteínas de Unión al ADN/metabolismo , Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/patología , MicroARNs/genética , ARN Circular/genética , Proteínas de Unión al ARN/metabolismo , Animales , Apoptosis , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Movimiento Celular , Proliferación Celular , Proteínas de Unión al ADN/genética , Femenino , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Invasividad Neoplásica , Pronóstico , Proteínas de Unión al ARN/genética , Tasa de Supervivencia , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The asymmetric unit of the title compound, C(7)H(8)N(4)S, contains two independent mol-ecules with slightly different conformations; the dihedral angles between the pyridine ring and mean plane of the thio-semicarbazone unit in the two mol-ecules are 2.88â (5) and 6.30â (5)°. Inter-molecular N-Hâ¯N and N-Hâ¯S hydrogen bonds link the mol-ecules into layers parallel to the ab plane.
RESUMEN
Hydrogen gas (H2), a multifunctional signaling molecule, has received increasing attention in recent years. In the present study, hydrogen-rich water (HRW) (2â¯ppm) was used for the processing of sprouted black barley (Hordeum distichum L.), and the results showed that the HRW treatment could significantly increase the germination rate and growth rate of black barley (Pâ¯<â¯0.05). A chemical component analysis showed that in sprouted black barley, the HRW treatment could change the distribution of phytochemicals (e.g., the ionic strength of guanosine), increase the concentrations of free vanillic acid, coumaric acid, sinapic acid, conjugated sinapic acid, Ca and Fe and the hydroxyl radical scavenging rate, and decrease the protein, fat, starch and dietary fibre contents compared with the results obtained after treatment with ultra-pure water (Pâ¯<â¯0.05). HRW can be used for the processing of sprouted grains to effectively increase their germination efficiency and concentrations of bioactive phytochemicals.
Asunto(s)
Hordeum/química , Hordeum/crecimiento & desarrollo , Hidrógeno/farmacología , Antioxidantes/análisis , Cromatografía Liquida , Fibras de la Dieta/análisis , Germinación/efectos de los fármacos , Hordeum/efectos de los fármacos , Radical Hidroxilo/análisis , Espectrometría de Masas , Proteínas de Vegetales Comestibles/análisis , Almidón/análisis , Agua/química , Agua/farmacologíaRESUMEN
In hepatocellular carcinoma (HCC), the hypoxic tumor microenvironment can drive enhance tumor malignancy and recurrence. The microRNA (miRNA) miR-196-5p has been shown to modulate the progression of several cancer types, but its roles in HCC remain uncertain. In the present report we observed significant miR-196-5p downregulation in HCC tissues and cells, and we found that the expression of this miRNA significantly impaired the proliferation and metastatic potential of HCC in vitro and in vivo. We identified high-mobility group AT-hook 2 (HMGA2) as a miR-196-5p target gene that was associated with the ability of miR-196-5p to modulate the progression of HCC. Expression of miR-196-5p and HMGA2 were correlated with the clinical characteristics and poor outcomes in patients with HCC. Finally, we found that hypoxic conditions were linked with reduced miR-196-5p expression in the context of HCC. Together these results highlight the role for miR-196-5p as an inhibitor of the proliferation and metastasis of HCC via the targeting of HMGA2, with this novel hypoxia/miR-196-5p/HMGA2 pathway serving as a potential target for future therapeutic intervention.
Asunto(s)
Carcinoma Hepatocelular/patología , Regulación hacia Abajo , Proteína HMGA2/genética , Neoplasias Hepáticas/patología , MicroARNs/genética , Regiones no Traducidas 3' , Animales , Carcinoma Hepatocelular/genética , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Masculino , Ratones , Trasplante de Neoplasias , Hipoxia TumoralRESUMEN
To assess the prevalence of antimicrobial resistance and class I integrons in Escherichia coli strains (n=58) isolated from bovine mastitis in Inner Mongolia, antimicrobial susceptibility and the presence of various types of integrons were characterized. Most isolates were susceptible to amikacin, colistin, ceftazidime, gentamicin and kanamycin, while those also exhibited high resistant incidence rates to ampicillin, amoxicillin, sulfadiazine and sulfamethoxydiazine. The integrase gene of integrons was amplified by PCR using degenerate primers. The integrons were confirmed by restriction fragment length polymorphism (RFLP) analysis of positive PCR products. Neither class II nor class III integron was detected, while 56.90% (n=33) of the isolates were positive for the presence of intI1 gene. Sequencing analysis of gene cassettes revealed that seven gene cassettes were found, which encoded resistance to trimethoprim (dfrA1 and dfrA17), aminoglycosides (aacA4, aadA1 and aadA5) and chloramphenicol (catB3), respectively. Of them, the gene cassette array dfrA17-aadA5 was found most prevalent (62.96%). The percentage of positive-integron among the isolates whose resistant profile was relatively broad (n> or =7) is 100.00%, while the one in narrow-profile isolates (n=2-6) is 30.56%. The correlation analysis revealed the incidence of integrons among the isolates were highly related to the resistant profile, indicating integrons play an important role in the dissemination and spread of the antimicrobial resistant strains.
Asunto(s)
Antiinfecciosos/farmacología , Farmacorresistencia Bacteriana/genética , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Integrones/genética , Mastitis Bovina/microbiología , Animales , Bovinos , China , Escherichia coli/aislamiento & purificación , Femenino , Integrasas/genética , Pruebas de Sensibilidad Microbiana , Datos de Secuencia MolecularRESUMEN
Additives can have a significant impact on the pyrolysis process. The effects of three additives (CaO, MSW char and biomass) on the pyrolysis characteristics of municipal solid waste (MSW) were investigated using a fixed-bed reactor. In addition, the effects of additives and temperature on the MSW pyrolysis product yield, the composition of MSW pyrolysis gases, and the composition of MSW pyrolysis tar were investigated using fixed bed reactor, GC-MS and FTIR, respectively. The results showed that the maximum tar yield of the MSW reached 28.73% at 600⯰C and the tar yield decreased with increasing amounts of CaO and MSW. The tar yield began to decrease when the additive amount of CaO was 5% and decreased to 23.05% when the additive amount of MSW char (C) was 30%. Synergistic pyrolysis of the biomass and MSW was observed when the additive amount of the pine increased to 75% (with a tar yield of 37.91%). Regarding gas composition, with increasing additives content, the CO2 yield decreased, while the CO yield increased. According to the FTIR analysis of the tar, CaO enhanced the condensation of the aromatic rings and converted the aliphatic hydrocarbons, while C reduced the oxygenic groups of the tar. The GC-MS results revealed that the additives decreased the yield of carboxylic acid and ethanol, and increased the ester yield. The additives were also found to have a deoxidation effect that decreased the acid content, potentially improving the quality and stability of the tar.
RESUMEN
Bigelovin, a sesquiterpene lactone, has been demonstrated to induce apoptosis, inhibit inflammation and angiogenesis in vitro, but its potential anti-metastatic activity remains unclear. In the present study, two colon cancer mouse models, orthotopic tumor allografts and experimental metastatic models were utilized to investigate the progression and metastatic spread of colorectal cancer after bigelovin treatments. Results showed that bigelovin (intravenous injection; 0.3-3â¯mg/kg) significantly suppressed tumor growth and inhibited liver/lung metastasis with modulation of tumor microenvironment (e.g. increased populations of T lymphocytes and macrophages) in orthotopic colon tumor allograft-bearing mice. Furthermore, the inhibitory activities were also validated in the experimental human colon cancer metastatic mouse model. The underlying mechanisms involved in the anti-metastatic effects of bigelovin were then revealed in murine colon tumor cells colon 26-M01 and human colon cancer cells HCT116. Results showed that bigelovin induced cytotoxicity, inhibition of cell proliferation, motility and migration in both cell lines, which were through interfering IL6/STAT3 and cofilin pathways. Alternations of the key molecules including Rock, FAK, RhoA, Rac1/2/3 and N-cadherin, which were detected in bigelovin-treated cancer cells, were also observed in the tumor allografts of bigelovin-treated mice. These findings strongly indicated that bigelovin has potential to be developed as anti-tumor and anti-metastatic agent for colorectal cancer.