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OBJECTIVE: This study assesses the influence of hyperkalemia on both disease severity and the risk of mortality among patients admitted to the emergency room. METHODS: This retrospective observational study utilized data from the Chinese Emergency Triage Assessment and Treatment database (CETAT, version 2.0), which was designed to evaluate and optimize management strategies for emergency room (ER) patients. Patients were systematically categorized based on serum potassium levels. Relationships between serum potassium levels, risk of mortality, and the severity of illness were then analyzed using multifactorial logistic regression and through Receiver Operating Characteristic (ROC) analysis. The effectiveness of various treatments at lowering potassium levels was also investigated. RESULTS: 12,799 emergency patients were enrolled, of whom 20.1% (n = 2,577) were hypokalemic and 2.98% (n = 381) were hyperkalemic. Among hyperkalemic patients, the leading reasons for visiting the ER were altered consciousness 23.88% (n = 91), cardiovascular symptoms 22.31% (n = 85), and gastrointestinal symptoms 20.47% (n = 78). Comparative analysis with patients exhibiting normal potassium levels revealed hyperkalemia as an independent factor associated with mortality in the ER. Mortality risk appears to positively correlate with increasing potassium levels, reaching peaks when blood potassium levels ranged between 6.5 and 7.0. Hyperkalemia emerged as a strong predictor of death in the ER, with an Area Under the Curve (AUC) of 0.89. The most frequently prescribed treatment for hyperkalemia patients was diuretics (57.32%, n = 188), followed by intravenous sodium bicarbonate (50.91%, n = 167), IV calcium (37.2%, n = 122), insulin combined with high glucose (27.74%, n = 91), and Continuous Renal Replacement Therapy (CRRT) for 19.82% (n = 65). Among these, CRRT appeared to be the most efficacious at reducing potassium levels. Diuretics appeared relatively ineffective, while high-glucose insulin, sodium bicarbonate, and calcium preparations having no significant effect on the rate of potassium decline. CONCLUSION: Hyperkalemia is common in emergency situations, especially among patients with altered consciousness. There is a strong positive correlation between the severity of hyperkalemia and mortality risk. CRRT appears to be the most effective potassium reducting strategy, while the use of diuretics should be approached with caution.
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Serviço Hospitalar de Emergência , Hiperpotassemia , Unidades de Terapia Intensiva , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , China/epidemiologia , Mortalidade Hospitalar , Hiperpotassemia/mortalidade , Hiperpotassemia/terapia , Potássio/sangue , Estudos Retrospectivos , Curva ROC , Índice de Gravidade de Doença , Admissão do PacienteRESUMO
XBB, an Omicron subvariant of SARS-CoV-2 that began to circulate in late 2022, has been dominant in the US since early 2023. To quantify the impact of XBB on the progression of COVID-19, we propose a new mathematical model which describes the interplay between XBB and other SARS-CoV-2 variants at the population level and which incorporates the effects of reinfection. We apply the model to COVID-19 data in the US that include surveillance data on the cases and variant proportions from the New York City, the State of New York, and the State of Washington. Our fitting and simulation results show that the transmission rate of XBB is significantly higher than that of other variants and the reinfection from XBB may play an important role in shaping the pandemic/epidemic pattern in the US.
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BACKGROUND AND AIM: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive disease with the underlying mechanisms poorly understood. YTHDF1, an N6 -methyladenosine (m6 A) reader protein, has important physiological functions in regulation of tumor development. However, the effect of YTHDF1 on ICC progression remains unknown yet. METHODS: The expression level of YTHDF1 in human ICC tissue was examined in The Cancer Genome Atlas database and our cohort. The role of YTHDF1 was detected using two human ICC cell lines in vitro. An ICC tumorigenesis mouse model was established via hydrodynamic transfection of AKT/YAP plasmids. m6 A sequencing, RNA immunoprecipitation sequencing, and RNA sequencing were carried out to explore the mechanism of YTHDF1 modulating ICC progression. RESULTS: Here, we find that YTHDF1 is upregulated in ICC and associated with shorter survival of ICC patients. Depletion of YTHDF1 inhibits cell proliferation, migration, and invasion, while overexpression of wild-type YTHDF1, but not m6 A reader domain mutant YTHDF1, significantly enhances tumor cell growth and aggressive abilities in vitro. Moreover, overexpression of YTHDF1 promotes the AKT/YAP transfection-induced orthotopic ICC tumorigenesis and progression in vivo. Mechanistically, we identify that YTHDF1 regulates the translation of epidermal growth factor receptor (EGFR) mRNA via binding m6 A sites in the 3'-UTR of EGFR transcript, thus leading to aberrant activities of downstream signal pathways that impact tumor progression. CONCLUSIONS: Our data uncover the oncogenic function and m6 A reader-dependent mechanism of YTHDF1 in regulation of ICC progression. Restricting abnormal oncogenic mRNA translation by targeting YTHDF1 may be a novel and promising strategy for ICC treatment.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Animais , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Carcinogênese , Linhagem Celular Tumoral , Colangiocarcinoma/patologia , Receptores ErbB/genética , Receptores ErbB/metabolismo , Humanos , Camundongos , Biossíntese de Proteínas , Proteínas Proto-Oncogênicas c-akt , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismoRESUMO
Ethyl carbamate (EC) is a genotoxic and carcinogenic compound that is also a by-product of fermented foods (bread, sour milk, soy cheese, etc.) and alcoholic beverages (wine, sake, distilled liquor, etc.). Studies have showed that ethyl carbamate is ingested by humans primarily through the consumption of alcoholic beverages. Many countries have thus established EC limits for alcoholic beverages. Chinese liquor (Baijiu) is a traditional and unique distilled liquor, which has a huge consumption in China due to its excellent color, flavor, and taste. Therefore, the control of EC in Chinese liquor is of great significance. This review summarized for the first time the progress in presence level, analysis method, formation mechanism, and elimination strategy of EC of Chinese liquor in recent decades. KEY POINTS: ⢠GC-MS and HPLC are the main methods to quantify EC in Chinese liquor. ⢠EC is formed in the fermentation, distillation, and storage stage. ⢠EC content can be reduced from raw material, microorganism, and production process.
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Uretana , Vinho , Bebidas Alcoólicas/análise , China , Fermentação , Aromatizantes , Humanos , Uretana/análise , Vinho/análiseRESUMO
AIM: Curcumin induces cytotoxic cell death in several human cancer cells. Here, we have investigated the effects of curcumin on non-small-cell lung cancer (NSCLC) with an aim to identify underlying mechanisms of its cytotoxic effect. MATERIALS & METHODS: The effects of various concentrations of curcumin on the NSCLC cell lines A549 and SPC-A1 were evaluated by MTT assay, colony-forming assay and flow cytometry. Additionally, protein expression associated with different signaling pathways was assessed using western blotting. RESULTS: Curcumin exhibited cytotoxicity against NSCLC, evident from the inhibition of cell proliferation, G2/M arrest, DNA damage, endoplasmic reticulum stress and mitochondrial apoptosis. The anticancer effect was related to reactive oxygen species (ROS) accumulation and could be reversed by ROS scavengers, catalase and N-acetyl-l-cysteine. Curcumin decreased mitochondrial transmembrane potential and induced ROS production, thereby activating the DNA damage/repair pathway and mitochondrial apoptosis. CONCLUSION: These results indicate that curcumin could be an effective therapeutic candidate for NSCLC.
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Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Curcumina/farmacologia , Neoplasias Pulmonares/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacosRESUMO
While overexpression of FSCN1 is reported in several cancers, the prognostic significance of FSCN1 in renal cell carcinoma (RCC) and the molecular mechanisms involved remain largely unclear. We retrospectively enrolled 194 patients with non-metastatic clear-cell RCC undergoing nephrectomy in our center between 2008 and 2011. FSCN1 expression was assessed by immunohistochemical staining and its association with clinicopathologic features and survival were evaluated. Functional effects of a modulated FSCN1 expression were analyzed with regard to invasion in RCC cell lines and metastasis in vivo. Here, we reported that FSCN1 was up-regulated in RCC tissues compared to non-tumor tissues, and associated with poor overall survival and recurrence-free survival. Its expression was not associated with age, tumor size, and clinical TNM stage. The incorporation of FSCN1 into the T stage and histologic grade would help to refine individual risk stratification. Preclinical studies using multiple RCC cells and orthotopic xenografts mice model indicated that FSCN1 could promote RCC cell invasion in vitro, and metastasis in vivo. Mechanistically, overexpression of FSCN1 led to an up-regulation of MMP9 and N-Cadherin. Notably, treating RCC cells with PI3 K/AKT inhibitors or knockdown GSK-3ß decreased the expression of FSCN1, and then attenuated RCC invasion. Together, our results demonstrate that FSCN as an oncogene is a potential novel prognostic biomarker for RCC patients after nephrectomy, and can promote RCC metastasis.
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Carcinoma de Células Renais/enzimologia , Proteínas de Transporte/metabolismo , Neoplasias Renais/enzimologia , Proteínas dos Microfilamentos/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Idoso , Animais , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/cirurgia , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Movimento Celular , Progressão da Doença , Feminino , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Camundongos Nus , Proteínas dos Microfilamentos/genética , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Intervalo Livre de Progressão , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de SinaisRESUMO
NR3C2 has previously been described as a tumor suppressor gene in several cancers; however the prognostic significance and biological function of NR3C2 in patients with non-metastatic clear cell renal cell carcinoma (ccRCC) remain largely unclear. The prognostic value of NR3C2 expression was evaluated using data from The Cancer Genome Atlas (TCGA) and 181 patients with non-metastatic ccRCC undergoing nephrectomy in our center. Predictive nomograms were generated and identified independent prognosticators to assess ccRCC patient overall survival (OS) and progression free survival (PFS) at 1, 5, and 8 years. The functional involvement of NR3C2 in RCC was examined in both in vitro and in vivo models upon overexpression of NR3C2. NR3C2 was found to be downregulated in tumor tissues and was correlated with several clinicopathological parameters, including the T status (p <0.001) and histological Fuhrman grade (p = 0.002). Both Cox regression analysis and Kaplan-Meier survival curves showed that low NR3C2 expression correlated with poor OS (HR = 2.21, p = 0.014) and PFS (HR = 1.71, p = 0.051). The incorporation of NR3C2 status into the T stage, UISS, or SSIGN scores helps to refine individual risk stratification. The newly built nomograms involving NR3C2 expression could better predict OS and PFS. Overexpression of NR3C2 inhibited RCC cell proliferation, colony formation, invasion, migration, and vasculogenic mimicry in vitro and reduced the growth of RCC xenografts in vivo. Together, these results suggest that NR3C2 may serve as a potential prognostic factor in non-metastatic ccRCC patients after nephrectomy and is involved in RCC oncogenesis.
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Biomarcadores Tumorais/análise , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Receptores de Mineralocorticoides/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/diagnóstico , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , PrognósticoRESUMO
Recently, ß-arrestin1 has been indicated as a prostate cancer promoter through promoting cell proliferation and epithelial to mesenchymal transition, but its underlying mechanism remains unclear. Here, our data revealed that ß-arrestin1 could promote cell growth through inhibiting the transcriptional activity and expression of FOXO3a in prostate cancer cells in vitro and in vivo. We found that ß-arrestin1 could promote the cell and tumor growth of prostate cancer, and ß-arrestin1 expression represented a negative correlation with FOXO3a expression but not FOXO1 expression in prostate cancer cell lines and tissues. In addition, forced expression of ß-arrestin1 induced a significant decrease of FOXO3a expression but had no clear effect on FOXO1 expression. Mechanistically, ß-arrestin1 could interact with FOXO3a and MDM2, respectively, and promote the interaction between FOXO3a and MDM2, whereas it had no obvious interaction with FOXO1. Furthermore, ß-arrestin1 could inhibit the transcriptional activity of FOXO3a via Akt and ERK1/2 pathways. Together, our results revealed a novel mechanism for ß-arrestin1 in the regulation of the prostate cancer procession through inhibiting FOXO3a.
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Proliferação de Células/genética , Proteína Forkhead Box O3/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias da Próstata/genética , beta-Arrestina 1/genética , Animais , Linhagem Celular Tumoral , Proteína Forkhead Box O3/metabolismo , Células HEK293 , Humanos , Masculino , Camundongos Nus , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Interferência de RNA , Transplante Heterólogo , Carga Tumoral/genética , beta-Arrestina 1/metabolismoRESUMO
OBJECTIVE: To establish a method for determination of 2,5-hexanedione in urine by headspace solid-phase microextraction-gas chromatography. METHODS: After extraction by solid-phase microextraction head, 2,5-hexanedione in urine was determined by gas chromatography and was quantified by external standard method. RESULTS: The concentration of 2,5-hexanedione in urine showed a linear relationship within the range of 0.1-20.0 µg/ml. The regression equation was y=261.36x-1.903 3, r=0.999 2. The minimum detectable concentration was 0.01 µg/ml. The recovery rate was 92.6%-97.1%, with a relative standard deviation (RSD) of 3.3%-5.8%. The intra-day and inter-day RSDs were 3.8%-6.2% and 4.7%-6.3% respectively. CONCLUSION: This determination method has no requirement for organic solvents, features simple and rapid operation, possesses higher detection sensitivity, and applies well to the determination of 2,5-hexanedione in urine.
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Cromatografia Gasosa , Hexanonas/urina , Microextração em Fase Sólida , Humanos , Sensibilidade e EspecificidadeRESUMO
Diquat (DQ) and paraquat (PQ) residues in food are potential hazards to consumers' health. Point-of-care testing (POCT) of them remains challenging. Based on surface-enhanced Raman spectroscopy (SERS) technology, we developed a POCT strategy for DQ and PQ on apple surface and in apple juice. A point-of-use composite was fabricated using a piece of porous melamine sponge (MS) modified with silver nanoflowers (AgNFs), combining the specificity of the SERS fingerprint and the excellent adsorption capacity of MS. Using this dual-functional AgNFs@MS, the on-site determination of the DQ and PQ residues was completed within 3 min without pretreatment. Clear trends were observed between SERS intensity and logarithmic concentrations, with r values from 0.962 to 0.984. The limit of detection of DQ and PQ were 0.14-0.70 ppb in apple juice and on apple surface. This study provides a new point-of-use alternative for rapidly detecting DQ and PQ residues in nonlaboratory settings.
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Diquat , Contaminação de Alimentos , Malus , Paraquat , Testes Imediatos , Prata , Análise Espectral Raman , Triazinas , Prata/química , Paraquat/análise , Triazinas/análise , Diquat/análise , Diquat/química , Malus/química , Contaminação de Alimentos/análise , Análise Espectral Raman/métodos , Resíduos de Praguicidas/análise , Resíduos de Praguicidas/química , Herbicidas/análise , Herbicidas/química , Nanopartículas Metálicas/química , Limite de Detecção , Sucos de Frutas e Vegetais/análiseRESUMO
Phthalic acid esters (PAEs) are ubiquitous environmental contaminants, and their real-time monitoring and removal remain challenging. Herein, a point-of-use (POU) device integrating adsorption, surface-enhanced Raman spectroscopy (SERS), and removal strategy was developed and realized ultrafast on-site determination of PAEs and cleanup of them from water. A piece of flexible melamine sponge (MS) was coated with gold nanostars (AuNSs) and metal-organic frameworks (MOFs), thus obtaining SERS activity and adsorption capacity. Based on this multifunctional AuNSs@MOFs/MS composite, clear trends were observed between SERS signal intensity and concentration of di(2-ethylhexyl)phthalate (DEHP) and dibutyl phthalate (DBP). The method detection limits of DEHP and DBP were calculated to be 0.75 × 10-7 and 0.67 × 10-7 M in water, respectively, proving good sensitivity. Furthermore, this POU device exhibited satisfactory adsorption capacity (â¼82.3 g/g for DBP and â¼90.0 g/g for DEHP), high adsorption efficiency (equilibrium in 100 s), and good regeneration capability (removal efficiency >70% after 5 cycles). The applicability of this device was verified by its good determination and removal performance in real environmental water matrices. The whole process could be completed within 5 min. This approach provides a new POU alternative for real-time monitoring and removal of PAEs in water.
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Paraquat (PQ) poisoning poses a significant public health concern. Unfortunately, point-of-care testing (POCT) of PQ in biofluids remains challenging. This study developed a portable kit that enables swift and reliable identification and quantification of PQ in human urine and gastric juice. The approach employed the surface-enhanced Raman scattering (SERS) technique, leveraging gold-silver core-shell nanoparticles (Au@Ag NPs) as the substrate. The kit comprised a portable Raman spectrometer and three sealed tubes containing Au@Ag NPs colloid, KI solution, and MgSO4 solution. A discernible correlation was observed between signal intensity and the logarithmic concentration, spanning from 5 to 500 µg/L in urine and 10 µg/L to 1 mg/L in gastric juice. The detection limits, calculated from the characteristic peak at 1648 cm -1, were 1.36 and 4.05 µg/L in human urine and gastric juice, respectively. Notably, this POCT kit obviated the need for pretreatment procedures, and the detection process was accomplished within 1 min, yielding satisfactory recoveries. This expeditious time frame is crucial for clinical diagnosis and rescue operations. Compared to conventional methods, this kit demonstrated real-time determinations in nonlaboratory settings. The simplicity and practicality of this POCT assay suggest its significant potential as an innovative alternative for poisoning detection applications.
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The monitoring of polybrominated diphenyl ethers (PBDEs) is of great significance owing to their high persistence, bioaccumulation, and toxicity to humans and animals. In this study, a sensitive and reproducible probe that integrates solid-phase microextraction and surface-enhanced Raman spectroscopy (SPME-SERS) was developed for screening PBDEs in multiphase specimens, including live fish, water, and electrical products. A roughed Cu fiber with an Ag layer was fabricated with dual functions. BDE-15 was readily extracted and detected on the SPME-SERS probe consisting of propanethiol-modified Ag nanoplates on a Cu wire. A clear linear relationship (R2 = 0.988) was established between the SERS intensity at 782 cm-1 and the logarithmic concentrations (from 100 ppb to 100 ppm), with a detection limit of 15 ppb. This proposed method enables continuous in vivo monitoring in fish without complicated pretreatments. The results obtained by this SPME-SERS approach were validated by high-performance liquid chromatography and showed good agreement. This "extracting and detecting" SPME-SERS method provides a potential tool to monitor the occurrence, formation, and migration of PBDEs.
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Éteres Difenil Halogenados , Microextração em Fase Sólida , Animais , Humanos , Éteres Difenil Halogenados/análise , Microextração em Fase Sólida/métodos , Análise Espectral Raman/métodos , ÁguaRESUMO
The widespread use and exposure of coumatetralyl (CMTT) has led to its accumulation in the environment and organisms, causing damage to ecosystems and adverse health effects in humans. Unfortunately, achieving fast detection of CMTT remains challenging. Herein, a rapid and robust surface-enhanced Raman spectroscopy (SERS) method was developed for rapid on-site detection of CMTT in environmental water and human urine. Clear trends were observed between the signal intensity and the logarithmic concentration of CMTT, ranging from 0.025 to 5.0 µg/mL with high reproducibility. The detection limits in water and human urine were as low as 1.53 and 13.71 ng/mL, respectively. The recoveries of CMTT for environmental water and urine samples were 90.2-98.2 and 82.0-87.5%, respectively, satisfactory for practical applications. The quantitative results of this approach were highly comparable to those obtained by high-performance liquid chromatography. Most importantly, it is cost-effective, operationally simple, and without a complicated sample preparation step. Detecting CMTT in water samples took only 5 min, and the detection of urine samples was completed within 8 min. This simple yet practical SERS approach offers a reliable application prospect for on-site CMTT detection in environmental water and point-of-care monitoring of poisoned patients.
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The use of Chinese herbs containing aristolochic acid can induce the exchange of adenine and thymine in gene mutations and even cause liver cancer. To eliminate the harm of aristolochic acids (AAs) to humans, a rapid and robust method of AAs screening is a prerequisite. In this work, a facile and robust Surface-enhanced Raman spectroscopy (SERS) method was used for the qualitative and quantitative detection of AAs in Chinese medicinal herbal preparations based on the mandelic acid modified Ag nanoparticles SERS substrate. Qualitative and quantitative SERS detection of Aristolochic acid I (AAI) was achieved with a good linear relationship ranging from 0.2 - 120.0 µM and a limit of detection (LOD) of 0.06 µM. The proposed method demonstrates a refined strategy for sensitivity analysis of AAs with the advantages of easy operation, time-saving, high sensitivity, and molecular specificity, making it a preferred platform for the screening of AAI in regular inspections of herbal products and regulatory supervision of the supply chain.
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Ácidos Aristolóquicos , Medicamentos de Ervas Chinesas , Nanopartículas Metálicas , Humanos , Ácidos Aristolóquicos/análise , Preparações de Plantas/análise , Análise Espectral Raman , Medicamentos de Ervas Chinesas/análise , Prata/análise , ChinaRESUMO
C-reactive protein (CRP) participates in human inflammatory responses and is an important indicator in clinical diagnoses. At present, the use of monoclonal antibodies to detect CRP in the human body is high, but they are unstable and expensive. Understanding the CRP expression pathway is of great significance for developing CRP tests and reagents. Chlamydomonas reinhardtii is a model organism that has great potential as a foreign protein expression system. This study is the first attempt to express human CRP in C. reinhardtii. We selected the endogenous constitutive Rbcs2 promoter and terminator and used ble as a selective gene to construct a C. reinhardtii nuclear expression vector containing CRP. After transformation using the glass bead method, six positive transformants were obtained. At the molecular level, full-length CRP was transformed into the genome of C. reinhardtii CC400 cells, and human CRP was expressed. This study provides new insights into obtaining active CRP. PRACTICAL APPLICATIONS: Based on the nuclear transformation system of C. reinhardtii, it can construct an exogenous protein expression system that produces a variety of high value-added products and can be used to produce a variety of high value-added proteins, functional drugs, and industrial raw materials. It has broad market prospects and huge application prospects.
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Chlamydomonas reinhardtii , Proteína C-Reativa/genética , Proteína C-Reativa/metabolismo , Chlamydomonas reinhardtii/genética , Chlamydomonas reinhardtii/metabolismo , Humanos , Regiões Promotoras GenéticasRESUMO
Myocardial infarction is one of the most severe heart diseases, leading to sudden death. Currently, angiography and stenting are widely performed in clinics, yet more effective treatment is still needed. Herein, we presented that dioscin, a natural product, showed protective effect on infarcted hearts via mitochondrial maintenance. Upon dioscin treatment, cardiac dysfunction was alleviated, and remodeling is prevented. Mechanistically, disocin maintains mitochondria function through the maintenance of Kreb's cycle, and suppresion of ROS accumulation. In this way, by targeting mitochondrial dysfunction, dioscin is a potential drug for infarcted hearts.
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miR-205-5p plays a vital role in the inflammation of allergic rhinitis (AR). The study is designed to investigate the effects and mechanism of miR-205-5p in AR in vivo and in vitro. An OVA-induced mice model and anti-DNP IgE-induced RBL-2H3 cell model were established. The pathological alterations in the nasal mucosa were evaluated by hematoxylin-eosin (HE) staining. IgE and histamine levels were detected by corresponding kits and the expressions of PEBP1, High mobility group box-1 (HMGB1) and Toll-like receptor 4 (TLR4) were detected by western blot. The association of miR-205-5p and PEBP1 was determined by dual-luciferase reported assay. ß-hexosaminidase activity was to evaluate the degranulation of RBL-2H3 cell. The pathological injury of nasal mucosa was significantly improved by miR-205-5p inhibition compared to AR mice. Following the treatment of miR-205-5p inhibitor, the levels of helper T cell (Th1) cytokines, interleukin (IL)-2 and interferon-γ (IFN-γ) were increased, while the levels of Th2 cytokines, IL-4 and IL-13, as well as the levels of IgE and histamine were markedly decreased in AR mice. We further found that miR-205-5P inhibition induced increased expression of PEBP1 and decreased expressions of HMGB1and TLR4. In vitro, miR-205-5P was verified to bind to PEBP1. PEBP1 silencing led to the reverse of miR-205-5p effects on decreasing the levels of ß-hexosaminidase activity and histamine, as well as the expressions of HMGB1 and TLR4 on anti-DNP IgE-induced RBL-2H3 cells. Our results indicate that miR-205-5P inhibition may ameliorate pathological injury via PEBP1. MiR-205-5P/ PEBP1 could be potential drug targets in AR.
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Proteína HMGB1 , MicroRNAs , Rinite Alérgica , Animais , Citocinas/metabolismo , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Histamina/uso terapêutico , Liberação de Histamina , Imunoglobulina E/metabolismo , Imunoglobulina E/uso terapêutico , Camundongos , MicroRNAs/metabolismo , Proteína de Ligação a Fosfatidiletanolamina/metabolismo , Proteína de Ligação a Fosfatidiletanolamina/uso terapêutico , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/genética , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , beta-N-Acetil-Hexosaminidases/genética , beta-N-Acetil-Hexosaminidases/metabolismo , beta-N-Acetil-Hexosaminidases/uso terapêuticoRESUMO
Chlamydomonas reinhardtii is a model organism with three sequenced genomes capable of genetic transformation. C. reinhardtii has the advantages of being low cost, non-toxic, and having a post-translational modification system that ensures the recombinant proteins have the same activity as natural proteins, thus making it a great platform for application in molecular biology and other fields. In this review, we summarize the existing methods for nuclear transformation of C. reinhardtii, genes for selection, examples of foreign protein expression, and factors affecting transformation efficiency, to provide insights into effective strategies for the nuclear transformation of C. reinhardtii.
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Núcleo Celular , Chlamydomonas reinhardtii , Genoma de Planta , Proteínas de Plantas , Transformação Genética , Núcleo Celular/genética , Núcleo Celular/metabolismo , Chlamydomonas reinhardtii/genética , Chlamydomonas reinhardtii/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismoRESUMO
A esterase gene was characterized from a halophilic bacterium Chromohalobacter canadensis which was originally isolated from a salt well mine. Sequence analysis showed that the esterase, named as EstSHJ2, contained active site serine encompassed by a conserved pentapeptide motif (GSSMG). The EstSHJ2 was classified into a new lipase/esterase family by phylogenetic association analysis. Molecular weight of EstSHJ2 was 26 kDa and the preferred substrate was p-NP butyrate. The EstSHJ2 exhibited a maximum activity at 2.5 M NaCl concentration. Intriguingly, the optimum temperature, pH and stability of EstSHJ2 were related to NaCl concentration. At 2.5 M NaCl concentration, the optimum temperature and pH of EstSHJ2 were 65 â and pH 9.0, and enzyme remained 81% active after 80 â treatment for 2 h. Additionally, the EstSHJ2 showed strong tolerance to metal ions and organic solvents. Among these, 10 mM K+, Ca2+ , Mg2+ and 30% hexane, benzene, toluene has significantly improved activity of EstSHJ2. The EstSHJ2 was the first reported esterase from Chromohalobacter canadensis, and may carry considerable potential for industrial applications under extreme conditions.