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1.
Molecules ; 28(5)2023 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-36903326

RESUMEN

Ficus pandurata Hance (FPH) is a Chinese herbal medicine widely used for health care. This study was designed to investigate the alleviation efficacy of the low-polarity ingredients of FPH (FPHLP), prepared by supercritical CO2 fluid extraction technology, against CCl4-induced acute liver injury (ALI) in mice and uncover its underlying mechanism. The results showed that FPHLP had a good antioxidative effect determined by the DPPH free radical scavenging activity test and T-AOC assay. The in vivo study showed that FPHLP dose-dependently protected against liver damage via detection of ALT, AST, and LDH levels and changes in liver histopathology. The antioxidative stress properties of FPHLP suppressed ALI by increasing levels of GSH, Nrf2, HO-1, and Trx-1 and reducing levels of ROS and MDA and the expression of Keap1. FPHLP significantly reduced the level of Fe2+ and expression of TfR1, xCT/SLC7A11, and Bcl2, while increasing the expression of GPX4, FTH1, cleaved PARP, Bax, and cleaved caspase 3. The results demonstrated that FPHLP protected mouse liver from injury induced by CCl4 via suppression of apoptosis and ferroptosis. This study suggests that FPHLP can be used for liver damage protection in humans, which strongly supports its traditional use as a herbal medicine.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas , Ferroptosis , Ficus , Animales , Ratones , Antioxidantes/farmacología , Apoptosis , Dióxido de Carbono/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Ficus/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Hígado , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo
2.
Environ Monit Assess ; 195(1): 41, 2022 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-36301357

RESUMEN

The amount of China's sulfur dioxide emission remains significantly large in recent years. To further reduce sulfur dioxide emission, the key is to find out the leading factors affecting sulfur dioxide emission and then take measures to control it accordingly. In order to investigate the influential factors of sulfur dioxide emission of various provinces, the data of sulfur dioxide emission of 30 provinces in China from 2001 to 2020 were collected. We established the symbolic regression model to explore the relationship between the GDP (x1), total population (x2), total energy consumption (x3), thermal power installed capacity (x4), and sulfur dioxide emission (dependent variable) for each province. The results show that the amount of China's total sulfur dioxide emission and sulfur dioxide emission in most provinces meet the environmental Kuznets curve (EKC). The influential degree of the factors affecting China's sulfur dioxide emission are GDP, total energy consumption, thermal power installed capacity, and total population. The provinces with the primary factor of GDP have the lowest average total energy consumption and average thermal power installed capacity, and their average sulfur dioxide emissions are also relatively low. The provinces with the primary factor of GDP do not show obvious geographical characteristics, but the provinces with the primary factor of total energy consumption are all distributed in southern China. Based on the research results, some control measures are also put forward.


Asunto(s)
Dióxido de Carbono , Dióxido de Azufre , Dióxido de Azufre/análisis , Dióxido de Carbono/análisis , Monitoreo del Ambiente , China , Desarrollo Económico , Carbono
3.
J Med Virol ; 93(11): 6210-6219, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34260071

RESUMEN

To investigate the role of miR-4301 in rotavirus (RV)-infected Caco-2 cells. In this experiment, RNAs of RV-infected Caco-2 cells were extracted, and the high-throughput second-generation sequencing was performed to detect the expression profiles of host microRNAs (miRNAs). Synthetic miRNA mimics and inhibitors were examined (quantitative polymerase chain reaction [qPCR], crystalline violet, immunofluorescence and electron microscopy) to evaluate the effect on RV replication. Target genes of miR-4301 were predicted by software analysis. The expression of target genes was evaluated by qPCR and Western blot after transfected with miRNA inhibitor/mimic, and crystalline violet and qPCR were used to detect the downregulation effects of target genes on RV replication. By transfecting miRNA inhibitors/mimics and detecting downstream target genes, the mechanism of miRNA affecting RV replication was analyzed. There were 78 known miRNAs with significant differential expression, including 39 upregulated miRNAs and 39 downregulated miRNAs. The results showed that miR-4301 exerted a key role in enhancing RV replication. PPP1R3D protein which can inhibit RV replication was predicted as the target gene of miR-4301 by software analysis. While upregulating miR-4301 by RV, the expression of PPP1R3D and glycogen synthase (GS) is suppressed. For the first time, the effect of miR-4301 on RV infection, and its influence on GS was investigated. Specifically, RV inhibits host cell glycogen synthesis to utilize the host intracellular glucose for promoting its own replication.


Asunto(s)
MicroARNs/inmunología , Proteína Fosfatasa 1/metabolismo , Infecciones por Rotavirus/genética , Infecciones por Rotavirus/inmunología , Rotavirus/inmunología , Replicación Viral/inmunología , Células CACO-2 , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Proteína Fosfatasa 1/genética , Rotavirus/genética
4.
J Acoust Soc Am ; 149(3): 2027, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33765777

RESUMEN

This paper presents a boundary element-based scheme for the sensitivity analysis of acoustic eigenfrequencies of both interior and exterior acoustic systems. The nonlinear eigenvalue problem generated by the acoustic boundary element method is first reformulated into a generalized eigenvalue problem of reduced dimension through a contour integral approach. The sensitivity formulations for acoustic eigenfrequencies are then derived based on an adjoint method that uses both the right and left eigenvectors. The adaptive cross approximation in conjunction with the hierarchical matrices is used to reduce the solution burden of the boundary element systems. The Burton-Miller-type combined formulation is applied to shift the spurious eigenfrequencies and their sensitivities, and the strategies to identify the spurious results are suggested. Three numerical examples are used to verify the accuracy and applicability of the developed scheme.

5.
Virus Genes ; 53(3): 367-376, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28289928

RESUMEN

Rotavirus (RV) is the most common cause of severe gastroenteritis and fatal dehydration in human infants and neonates of different species. However, the pathogenesis of rotavirus-induced diarrhea is poorly understood. Secretory diarrhea caused by rotavirus may lead to a combination of excessive secretion of fluid and electrolytes into the intestinal lumen. Fluid absorption in the small intestine is driven by Na+-coupled transport mechanisms at the luminal membrane, including Na+/H+ exchanger (NHE). Here, we performed qRT-PCR to detect the transcription of NHEs. Western blotting was employed for protein detection. Furthermore, immunocytochemistry was used to validate the NHE's protein expression. Finally, intracellular Ca2+ concentration was detected by confocal laser scanning microscopy. The results demonstrated that the NHE6 mRNA and protein expressed in the human colon adenocarcinoma cell line (Caco-2). Furthermore, RV-Wa induced decreased expression of the NHE1 and NHE6 in Caco-2 cell in a time-dependent manner. In addition, intracellular Ca2+ concentration in RV-Wa-infected Caco-2 cells was higher than that in the mock-infected cells. Furthermore, RV-Wa also can downregulate the expression of calmodulin (CaM) and calmodulin kinase II (CaMKII) in Caco-2 cells. These findings provides important insights into the mechanisms of rotavirus-induced diarrhea. Further studies on the underlying pathophysiological mechanisms that downregulate NHEs in RV-induced diarrhea are required.


Asunto(s)
Regulación hacia Abajo , Regulación de la Expresión Génica/genética , Rotavirus/patogenicidad , Intercambiador 1 de Sodio-Hidrógeno/genética , Intercambiadores de Sodio-Hidrógeno/genética , Animales , Células CACO-2 , Calcio/análisis , Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Calmodulina/genética , Calmodulina/metabolismo , Línea Celular , Citosol/química , Diarrea/virología , Humanos , Macaca mulatta , ARN Mensajero/análisis , ARN Mensajero/biosíntesis , Infecciones por Rotavirus/genética , Infecciones por Rotavirus/virología , Intercambiador 1 de Sodio-Hidrógeno/metabolismo , Intercambiadores de Sodio-Hidrógeno/metabolismo , Transcripción Genética
6.
Toxicol Appl Pharmacol ; 298: 1-8, 2016 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-26965727

RESUMEN

Methylmercury (MeHg) is a highly neurotoxic environmental chemical that can cause developmental impairments. Human fetuses and neonates are particularly susceptible to MeHg toxicity; however, the mechanisms governing its effects in the developing brain are unclear. In the present study, we investigated the effects of prenatal and lactational MeHg exposure on the developing cerebellum in rats. We demonstrated that exposure to 5ppm MeHg decreased postnatal expression of pre- and postsynaptic proteins, suggesting an impairment in synaptic development. MeHg exposure also reduced neurite outgrowth, as shown by a decrease in the expression of the neurite marker neurofilament H. These changes were not observed in rats exposed to 1ppm MeHg. In order to define the underlying mechanism, we investigated the effects of MeHg exposure on the tropomyosin receptor kinase (Trk) A pathway, which plays important roles in neuronal differentiation and synapse formation. We demonstrated suppression of the TrkA pathway on gestation day 20 in rats exposed to 5ppm MeHg. In addition, down-regulation of eukaryotic elongation factor 1A1 (eEF1A1) was observed on postnatal day 1. eEF1A1 knockdown in differentiating PC12 cells impaired neurite outgrowth and synaptic protein expression, similar to the results of MeHg exposure in the cerebellum. These results suggest that suppression of the TrkA pathway and subsequent decreases in eEF1A1 expression induced by prenatal exposure to MeHg may lead to reduced neurite outgrowth and synaptic protein expression in the developing cerebellum.


Asunto(s)
Cerebelo/efectos de los fármacos , Contaminantes Ambientales/toxicidad , Compuestos de Metilmercurio/toxicidad , Neuritas/efectos de los fármacos , Factor 1 de Elongación Peptídica/genética , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Receptor trkA/antagonistas & inhibidores , Sinapsis/efectos de los fármacos , Animales , Western Blotting , Cerebelo/crecimiento & desarrollo , Cerebelo/metabolismo , Cerebelo/patología , Relación Dosis-Respuesta a Droga , Regulación hacia Abajo , Femenino , Masculino , Neuritas/patología , Células PC12 , Embarazo , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/patología , Ratas , Ratas Wistar , Sinapsis/genética
7.
Yao Xue Xue Bao ; 51(10): 1622-8, 2016 10.
Artículo en Zh | MEDLINE | ID: mdl-29932618

RESUMEN

The study was designed to generate an ophthalmic thermosensitive in situ gel with improved mechanical and mucoadhesive properties that may prolong the retention time to enhance the bioavalability of pearl hydrolyzate. The gene was comprised of poloxamer 407, poloxamer188 and Carbopol 934, which were optimized by central composite design and response surface methodology. The rheological properties, transcorneal permeability, retention time and in vitro release behaviors of the optimal gel formulation were investigated. The gel was Newtonian liquid at 25 ℃ and performed as a semisolid gel with non-Newtonian liquid property with a gelation time of 13 s at 35 ℃. Compared with a conventional eye drops, the ophthalmic in situ gel exhibited a sevenfold increase in retention with a sustained release behavior, which was observed with suitable permeability coefficient at 5.58 cm·s-1. In conclusion, the new gel of pearl hydrolyzate prolonged the release duration of drug, which may decrease the frequency of administration of pearl hydrolyzate.


Asunto(s)
Acrilatos/química , Geles/química , Soluciones Oftálmicas/química , Poloxámero/química , Animales , Preparaciones de Acción Retardada , Ojo/efectos de los fármacos , Reología , Temperatura
8.
Arch Virol ; 160(6): 1421-33, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25877820

RESUMEN

Rotavirus (RV) is the primary cause of severe dehydrating gastroenteritis and acute diarrheal disease in infants and young children. Previous studies have revealed that genistein can inhibit the infectivity of enveloped or nonenveloped viruses. Although the biological properties of genistein are well studied, the mechanisms of action underlying their anti-rotavirus properties have not been fully elucidated. Here, we report that genistein significantly inhibits RV-Wa replication in vitro by repressing viral RNA transcripts, and possibly viral protein synthesis. Interestingly, we also found that aquaporin 4 (AQP4) mRNA and protein expression, which was downregulated in RV-infected Caco-2 cells, can be upregulated by genistein in a time- and dose-dependent manner. Further experiments confirmed that genistein triggers CREB phosphorylation through PKA activation and subsequently promotes AQP4 gene transcription. These findings suggest that the pathophysiological mechanism of RV infection involves decreased expression of AQP4 and that genistein may be a useful candidate for developing a new anti-RV strategy by inhibiting rotavirus replication and upregulating AQP4 expression via the cAMP/PKA/CREB signaling pathway. Further studies on the effect of genistein on RV-induced diarrhea are warranted.


Asunto(s)
Antivirales/uso terapéutico , Acuaporina 4/biosíntesis , Células CACO-2/virología , Genisteína/uso terapéutico , Infecciones por Rotavirus/tratamiento farmacológico , Replicación Viral/efectos de los fármacos , Adenilil Ciclasas/metabolismo , Antivirales/farmacología , Acuaporina 4/fisiología , Células CACO-2/efectos de los fármacos , Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo , Relación Dosis-Respuesta a Droga , Electroforesis en Gel de Poliacrilamida , Técnica del Anticuerpo Fluorescente Indirecta , Genisteína/farmacología , Humanos , Immunoblotting , Reacción en Cadena en Tiempo Real de la Polimerasa , Rotavirus/efectos de los fármacos , Rotavirus/fisiología , Regulación hacia Arriba/efectos de los fármacos
9.
J Environ Sci (China) ; 34: 107-15, 2015 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-26257353

RESUMEN

In order to assess the potential health risks of Hg pollution, total mercury (T-Hg) and methyl mercury (MeHg) concentrations were determined in air, dust, surface soil, crops, poultry, fish and human hair samples from an electronic waste (e-waste) recycling area in Taizhou, China. High concentrations of T-Hg and MeHg were found in these multiple matrices, and the mean concentration was 30.7 ng/m(3) of T-Hg for atmosphere samples, 3.1 µg/g of T-Hg for soil, 37.6 µg/g of T-Hg for dust, 20.3 ng/g of MeHg for rice and 178.1 ng/g of MeHg for fish, suggesting that the e-waste recycling facility was a significant source of Hg. The inorganic Hg (I-Hg) levels (0.84 µg/g) in hair samples of e-waste workers were much higher than that in the reference samples. Pearson's correlation coefficients showed that strong positive correlations (p<0.01) between hair I-Hg and time staying in industrial area (r=0.81) and between MeHg and fish consumption frequency (r=0.91), imply that workers were mainly exposed to Hg vapor through long-time inhalation of contaminated air and dust, while other population mainly exposed to MeHg through high-frequency fish consumption. The estimated daily intakes of Hg showed that dietary intake was the major Hg exposure source, and Hg intakes from rice and fish were significantly higher than from any other foods. The estimated total daily intakes (TDIs) of MeHg for both children (696.8 ng/(kg·day)) and adults (381.3 ng/(kg·day)) greatly exceeded the dietary reference dose (RfD) of 230 ng/(kg·day), implying greater health risk for humans from Hg exposures around e-waste recycling facilities.


Asunto(s)
Exposición a Riesgos Ambientales , Contaminantes Ambientales/análisis , Contaminación de Alimentos/análisis , Mercurio/análisis , Compuestos de Metilmercurio/análisis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , China , Polvo/análisis , Residuos Electrónicos , Monitoreo del Ambiente , Femenino , Cabello/química , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Exposición Profesional , Reciclaje , Instalaciones de Eliminación de Residuos , Adulto Joven
10.
Arch Gynecol Obstet ; 289(6): 1225-34, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24318276

RESUMEN

PURPOSE: The aim of this study was to evaluate the evidence for probiotic use in the treatment of bacterial vaginosis (BV) in adult women. METHODS: The Cochrane Library, PubMed, CINAHL and EMBASE databases were searched to identify the relevant randomized controlled trials that investigated the effects of probiotics for the treatment of BV. Two independent authors used an Excel file to extract data and assessed trial quality. The primary outcome measure was the cure rate of BV. The meta-analysis was performed with the fixed-effects model or random-effects model according to heterogeneity. RESULTS: A total of 1,304 patients from 12 trials were subjected to meta-analysis. The pooled result showed that probiotics supplementation can significantly improve the cure rate in adult BV patients [risk ratio (RR) 1.53; 95 % confidence interval (CI) 1.19-1.97]. Findings were slightly different when analyses were restricted to nine high-quality studies (RR 1.60; 95 % CI 1.16-2.22). In a subgroup meta-analysis, a statistically significant beneficial effect of probiotics was observed in Europe populations and short-term follow-up days. CONCLUSION: Compared with the control arm, the limited evidence suggests that probiotics show a beneficial effect in patients who are suffering from BV. However, the results should be interpreted cautiously because of the heterogeneity among study designs. Further large-scale, well-designed RCTs on this topic are urgently needed.


Asunto(s)
Probióticos/uso terapéutico , Vaginosis Bacteriana/tratamiento farmacológico , Administración Intravaginal , Administración Oral , Adulto , Antiinfecciosos/uso terapéutico , Quimioterapia Combinada , Femenino , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
11.
Virology ; 594: 110039, 2024 06.
Artículo en Inglés | MEDLINE | ID: mdl-38492520

RESUMEN

Porcine Epidemic Diarrhea Virus (PEDV) poses a significant threat to the global swine industry, demanding a thorough understanding of its cellular invasion mechanism for effective interventions. This study meticulously investigates the impact of O- and N-linked glycans on PEDV proteins and host cell interaction, shedding light on their influence on the virus's invasion process. Utilizing CRISPR-Cas9 technology to inhibit cell surface O- and N-linked glycan synthesis demonstrated no discernible impact on virus infection. However, progeny PEDV strains lacking these glycans exhibited a minor effect of O-linked glycans on virus infection. Conversely, a notable 40% reduction in infectivity was observed when the virus surface lacked N-linked glycans, emphasizing their pivotal role in facilitating virus recognition and binding to host cells. Additionally, inhibition studies utilizing kifunensine, a natural glycosidase I inhibitor, reaffirmed the significant role of N-linked glycans in virus infection. Inhibiting N-linked glycan synthesis with kifunensine substantially decreased virus entry into cells and potentially influenced spike protein expression. Assessment of the stability and recovery potential of N-linked glycan-deficient strains underscored the critical importance of N-glycans at various stages of the virus lifecycle. In vivo experiments infecting piglets with N-glycan-deficient strains exhibited milder clinical symptoms, reduced virus excretion, and less severe pathological lesions compared to conventional strains. These findings offer promising translational applications, proposing N-glycosylation inhibitors as potential therapeutic interventions against PEDV. The utilization of these inhibitors might mitigate virus invasion and disease transmission, providing avenues for effective antiviral strategies and vaccine development. Nonetheless, further research is warranted to elucidate the precise mechanisms of N-linked glycans in PEDV infection for comprehensive clinical applications.


Asunto(s)
Infecciones por Coronavirus , Virus de la Diarrea Epidémica Porcina , Enfermedades de los Porcinos , Animales , Porcinos , Virus de la Diarrea Epidémica Porcina/fisiología , Internalización del Virus , Procesamiento Proteico-Postraduccional , Polisacáridos
12.
Nanoscale ; 16(8): 4095-4104, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38333905

RESUMEN

In recent years, tumor catalytic therapy based on nanozymes has attracted widespread attention. However, its application is limited by the tumor hypoxic microenvironment (TME). In this study, we developed oxygen-supplying magnetic bead nanozymes that integrate hemoglobin and encapsulate the photosensitizer curcumin, demonstrating reactive oxygen species (ROS)-induced synergistic breast cancer therapy. Fe3O4 magnetic bead-mediated catalytic dynamic therapy (CDT) generates hydroxyl radicals (˙OH) through the Fenton reaction in the tumor microenvironment. The Hb-encapsulated Fe3O4 magnetic beads can be co-loaded with the photosensitizer/chemotherapeutic agent curcumin (cur), resulting in Fe3O4-Hb@cur. Under hypoxic conditions, oxygen molecules are released from Fe3O4-Hb@cur to overcome the TME hypoxia, resulting in comprehensive effects favoring anti-tumor responses. Upon near-infrared (NIR) irradiation, Fe3O4-Hb@cur activates the surrounding molecular oxygen to generate a certain amount of singlet oxygen (1O2), which is utilized for photodynamic therapy (PDT) in cancer treatment. Meanwhile, we validated that the O2 carried by Hb significantly enhances the intracellular ROS level, intensifying the catalytic therapy mediated by Fe3O4 magnetic beads and inflicting lethal damage to cancer cells, effectively inhibiting tumor growth. Therefore, significant in vivo synergistic therapeutic effects can be achieved through catalytic-photodynamic combination therapy.


Asunto(s)
Neoplasias de la Mama , Curcumina , Neoplasias , Fotoquimioterapia , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Oxígeno , Especies Reactivas de Oxígeno/farmacología , Curcumina/farmacología , Curcumina/uso terapéutico , Línea Celular Tumoral , Fotoquimioterapia/métodos , Neoplasias/tratamiento farmacológico , Hipoxia , Fenómenos Magnéticos , Microambiente Tumoral , Peróxido de Hidrógeno/uso terapéutico
13.
Nat Biomed Eng ; 8(2): 177-192, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37872368

RESUMEN

Cas13 can be used for the knockdown, editing, imaging or detection of RNA and for RNA-based gene therapy. Here by using RNA immunoprecipitation sequencing, transcriptome profiling, biochemical analysis, high-throughput screening and machine learning, we show that Cas13 can intrinsically target host RNA in mammalian cells through previously unappreciated mechanisms. Different from its known cis/trans RNA-cleavage activity, Cas13 can also cleave host RNA via mechanisms that are transcript-specific, independent of the sequence of CRISPR RNA and dynamically dependent on the conformational state of Cas13, as we show for several Cas13-family effectors encoded in one-vector and two-vector lentiviral systems. Moreover, host genes involved in viral processes and whose transcripts are intrinsically targeted by Cas13 contribute to constraining the lentiviral delivery and expression of Cas13. Our findings offer guidance for the appropriate use of lentiviral Cas13 systems and highlight the need for caution regarding intrinsic RNA targeting in Cas13-based applications.


Asunto(s)
Sistemas CRISPR-Cas , ARN , Animales , ARN/genética , Sistemas CRISPR-Cas/genética , Terapia Genética , Perfilación de la Expresión Génica , Lentivirus/genética , Mamíferos/genética
14.
Nat Commun ; 15(1): 5502, 2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38951519

RESUMEN

Resistance to chemotherapy has been a major hurdle that limits therapeutic benefits for many types of cancer. Here we systematically identify genetic drivers underlying chemoresistance by performing 30 genome-scale CRISPR knockout screens for seven chemotherapeutic agents in multiple cancer cells. Chemoresistance genes vary between conditions primarily due to distinct genetic background and mechanism of action of drugs, manifesting heterogeneous and multiplexed routes towards chemoresistance. By focusing on oxaliplatin and irinotecan resistance in colorectal cancer, we unravel that evolutionarily distinct chemoresistance can share consensus vulnerabilities identified by 26 second-round CRISPR screens with druggable gene library. We further pinpoint PLK4 as a therapeutic target to overcome oxaliplatin resistance in various models via genetic ablation or pharmacological inhibition, highlighting a single-agent strategy to antagonize evolutionarily distinct chemoresistance. Our study not only provides resources and insights into the molecular basis of chemoresistance, but also proposes potential biomarkers and therapeutic strategies against such resistance.


Asunto(s)
Antineoplásicos , Sistemas CRISPR-Cas , Resistencia a Antineoplásicos , Irinotecán , Oxaliplatino , Proteínas Serina-Treonina Quinasas , Resistencia a Antineoplásicos/genética , Humanos , Línea Celular Tumoral , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Oxaliplatino/farmacología , Irinotecán/farmacología , Sistemas CRISPR-Cas/genética , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/tratamiento farmacológico , Animales , Neoplasias/genética , Neoplasias/tratamiento farmacológico , Repeticiones Palindrómicas Cortas Agrupadas y Regularmente Espaciadas/genética , Ratones , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos
15.
Kidney Blood Press Res ; 38(1): 31-41, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-24525835

RESUMEN

BACKGROUND/AIMS: An increasing body of evidence demonstrates that L-carnitine plays a pivotal role in lipid metabolism of hemodialysis (HD) patients. However, there are still some reservations about its benefits. Therefore, we performed a meta-analysis to assess the effects of L-carnitine supplementation on lipid profile in HD patients. METHODS: Literature search was performed to identify the relevant randomized controlled trials that investigated the effects of L-carnitine on the lipid profile of subjects. Two independent authors used an Excel file to extract data and assess trials quality. The primary effect measure was the difference in means of the final lipid measurements between the intervention and control groups. The meta-analysis was performed with the fixed-effects model or random-effects model according to heterogeneity. RESULTS: Twelve studies with a total of 391 patients met the inclusion criteria. The use of L-carnitine was not associated with a reduction in the total cholesterol (SMD, -0.11; 95% CI, -0.31 to 0.09), HDL-cholesterol (SMD, 0.01; 95% CI, -0.36 to 0.39), VLDL-cholesterol (SMD, 0.54; 95% CI, -0.06 to 1.14), and the serum triglycerides (SMD, -0.12; 95% CI, -0.36 to 0.12). However, L-carnitine can significantly decrease the LDL-cholesterol (SMD, -0.29; 95% CI, -0.53 to -0.06) in HD patients. In a subgroup meta-analysis, a significant LDL-cholesterol-lowering effect of L-carnitine supplementation was observed in intravenous application group, and patients with longer interventional duration and renal diseases. CONCLUSION: The limited evidence suggests that there was no effect of L-carnitine on serum total cholesterol, HDL-cholesterol, VLDL-cholesterol and serum triglycerides. By contrast, this meta-analysis suggests a promising effect of L-carnitine on LDL-cholesterol. Further large-scale, well-designed randomized controlled trials are urgently needed


Asunto(s)
Carnitina/farmacología , Hipolipemiantes/farmacología , Lípidos/sangre , Diálisis Renal , Complejo Vitamínico B/farmacología , Animales , Suplementos Dietéticos , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto , Insuficiencia Renal/sangre , Insuficiencia Renal/terapia
16.
Phytomedicine ; 112: 154694, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36804757

RESUMEN

BACKGROUND: Atherosclerosis is the most prevalent cardiovascular disease and remains the major contributor to death and mortality globally. Salvianolic acid A (SalA) is a water-soluble phenolic acid that benefits atherosclerosis. However, the mechanisms of SalA protecting against atherosclerosis remain unclear. PURPOSE: We aimed to determine whether SalA prevents atherosclerosis by modulating 3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) degradation via the ubiquitin-proteasomal pathway. METHODS: The animal and cellular models of atherosclerosis were established by subjecting apolipoprotein E (ApoE) knockout mice to a high-fat diet (HFD) and exposing human umbilical vein endothelial cells (HUVECs) to oxidized low-density lipoprotein (ox-LDL), respectively. RESULTS: Our results showed that similar to atorvastatin, SalA suppressed atherosclerotic plaque formation, improved serum lipid accumulation, and reduced cholesterol levels in HFD-fed ApoE-/- mice. Moreover, SalA protected HUVECs from ox-LDL-caused cell viability reduction and lipid accumulation. The mechanism study revealed that SalA reduced the production of proinflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, and IL-6, and augmented the generation of the anti-inflammatory cytokine IL-10 in ApoE-/- mice and HUVECs, accompanied by increased HMGCR ubiquitination and degradation via translocation in renal carcinoma on chromosome 8 (Trc8), insulin-induced gene (Insig)1 and Insig2. Furthermore, the knockdown of Trc8 abolished the SalA-induced HMGCR degradation and anti-atherosclerosis activity. CONCLUSION: SalA rescues atherosclerosis by inhibiting inflammation through the Trc8-regulated degradation of HMGCR. These findings underscore Trc8 as a potential target of atherosclerosis.


Asunto(s)
Aterosclerosis , Células Endoteliales , Humanos , Animales , Ratones , Células Endoteliales/metabolismo , Aterosclerosis/tratamiento farmacológico , Aterosclerosis/metabolismo , Inflamación/etiología , Ratones Noqueados , Citocinas , Apolipoproteínas E/genética
17.
Nat Commun ; 14(1): 5386, 2023 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-37666839

RESUMEN

Droplet rebound is ubiquitous on super-repellent surfaces. Conversion between kinetic and surface energies suggests that rebound suppression is unachievable due to negligible energy dissipation. Here, we present an effective approach to suppressing rebounds by incorporating bubbles into droplets, even in super-repellent states. This suppression arises from the counteractive capillary effects within bubble-encapsulated hollow droplets. The capillary flows induced by the deformed inner-bubble surface counterbalance those driven by the outer-droplet surface, resulting in a reduction of the effective take-off momentum. We propose a double-spring system with reduced effective elasticity for hollow droplets, wherein the competing springs offer distinct behavior from the classical single-spring model employed for single-phase droplets. Through experimental, analytical, and numerical validations, we establish a comprehensive and unified understanding of droplet rebound, by which the behavior of single-phase droplets represents the exceptional case of zero bubble volume and can be encompassed within this overarching framework.

18.
Biomed Pharmacother ; 169: 115941, 2023 Dec 31.
Artículo en Inglés | MEDLINE | ID: mdl-38006619

RESUMEN

Chaenomeles sinensis fruit polysaccharide (CSP) and carboxymethylated CSP (CSP-M) were prepared using ultrasound extraction and the sodium hydroxide-chloroacetic acid method. Structural analysis revealed that both CSP and CSP-M mainly consisted of glucose, arabinose, rhamnose, glucuronic acid, galactose, and xylose, and the introduction of carboxymethyl did not damage the polymer chain of CSP. In vivo studies verified that both CSP and CSP-M could remarkably alleviate the symptoms of ulcerative colitis (UC) mice and reduce intestinal epithelial cell depletion, along with the infiltration of inflammatory cells in colon tissue, by mediating the expression of myeloperoxidase (MPO), inflammatory factors [tumour necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6], and oxidative stress factors [malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and nitric oxide (NO)]. Most importantly, the introduction of carboxymethyl significantly enhanced the anti-UC activity of CSP, confirming the efficacy of carboxymethylation as a method to enhance the biological activities of CSP, thereby suggesting the potential of CSP-M as a therapeutic option for UC.


Asunto(s)
Colitis Ulcerosa , Colitis , Rosaceae , Ratones , Animales , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/metabolismo , Sulfato de Dextran/efectos adversos , Inflamación/metabolismo , Colon/metabolismo , Estrés Oxidativo , Factor de Necrosis Tumoral alfa/metabolismo , Glutatión/metabolismo , Polisacáridos/efectos adversos , Modelos Animales de Enfermedad , Colitis/metabolismo
19.
Anim Nutr ; 14: 450-460, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37649679

RESUMEN

As a foodborne pathogen of global importance, Salmonella enterica serovar Enteritidis (S. Enteritidis) is a threat to public health that is mainly spread by poultry products. Intestinal Enterobacteriaceae can inhibit the colonization of S. Enteritidis and are regarded as a potential antibiotic substitute. We investigated, in chicks, the anti-S. Enteritidis effects of Escherichia coli (E. coli) Nissle 1917, the most well-known probiotic member of Enterobacteriaceae. Eighty 1-d-old healthy female AA broilers were randomly divided into 4 groups, with 20 in each group, namely the negative control (group P), the E. coli Nissle 1917-treated group (group N), the S. Enteritidis-infected group (group S) and the E. coli Nissle 1917-treated and S. Enteritidis-infected group (group NS). From d 5 to 7, chicks in groups N and NS were orally gavaged once a day with E. coli Nissle 1917 and in groups P and S were administered the same volume of sterile PBS. At d 8, the chicks in groups S and NS were orally gavaged with S. Enteritidis and in groups P and N were administered the same volume of sterile PBS. Sampling was conducted 24 h after challenge. Results showed that gavage of E. coli Nissle 1917 reduced the spleen index, Salmonella loads, and inflammation (P < 0.05). It improved intestinal morphology and intestinal barrier function (P < 0.05). S. Enteritidis infection significantly reduced mRNA expression of angiotensin-converting enzyme 2 (ACE2) and solute carrier family 6-member 19 (SLC6A19) in the cecum and the content of Gly, Ser, Gln, and Trp in the serum (P < 0.05). Pretreatment with E. coli Nissle 1917 yielded mRNA expression of ACE2 and SLC6A19 in the cecum and levels of Gly, Ser, Gln, and Trp in the serum similar to that of uninfected chicks (P < 0.05). Additionally, E. coli Nissle 1917 altered cecum microbiota composition and enriched the abundance of E. coli, Lactobacillales, and Lachnospiraceae. These findings reveal that the probiotic E. coli Nissle 1917 reduced S. Enteritidis infection and shows enormous potential as an alternative to antibiotics.

20.
Environ Sci Pollut Res Int ; 30(37): 87071-87086, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37418189

RESUMEN

Carbon emission (CE) has led to increasingly severe climate problems. The key to reducing CE is to identify the dominant influencing factors and explore their influence degree. The CE data of 30 provinces from 1997 to 2020 in China were calculated by IPCC method. Based on this, the importance order of six factors included GDP, Industrial Structure (IS), Total Population (TP), Population Structure (PS), Energy Intensity (EI) and Energy Structure (ES) affecting the CE of China's provinces were obtained by using symbolic regression, then the LMDI and the Tapio models were established to deeply explore the influence degree of different factors on CE. The results showed that the 30 provinces were divided into five categories according to the primary factor, GDP was the most important factor, followed by ES and EI, then IS, and the least TP and PS. The growth of per capita GDP promoted the increase of CE, while reduced EI inhibited the increase of CE. The increase of ES promoted CE in some provinces but inhibited in others. The increase of TP weakly promoted the increase of CE. These results can provide some references for governments to formulate relevant CE reduction policies under dual carbon goal.


Asunto(s)
Dióxido de Carbono , Carbono , Carbono/análisis , Dióxido de Carbono/análisis , China , Industrias , Desarrollo Económico
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