RESUMO
The development of nanomaterials for delivering natural compounds has emerged as a promising approach for atherosclerosis therapy. However, premature drug release remains a challenge. Here, we present a ROS-responsive biomimetic nanocomplex co-loaded with Geniposide (GP) and Emodin (EM) in nanoliposome particles (LP NPs) for targeted atherosclerosis therapy. The nanocomplex, hybridized with the macrophage membrane (Møm), effectively evades immune system clearance and targets atherosclerotic plaques. A modified thioketal (TK) system responds to ROS-rich plaque regions, triggering controlled drug release. In vitro, the nanocomplex inhibits endothelial cell apoptosis and macrophage lipid accumulation, restores endothelial cell function, and promotes cholesterol effluxion. In vivo, it targets ROS-rich atherosclerotic plaques, reducing plaque area ROS levels and restoring endothelial cell function, consequently promoting cholesterol outflow. Our study demonstrates that ROS-responsive biomimetic nanocomplexes co-delivering GP and EM exert a synergistic effect against endothelial cell apoptosis and lipid deposition in macrophages, offering a promising dual-cell therapy modality for atherosclerosis regression.
Assuntos
Aterosclerose , Emodina , Iridoides , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/tratamento farmacológico , Lipossomos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Emodina/farmacologia , Emodina/uso terapêutico , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , ColesterolRESUMO
PCSK9, which is closely related to atherosclerosis, is significantly expressed in vascular smooth muscle cells (VSMCs). Moreover, Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) mediated phenotypic transformation, abnormal proliferation, and migration of VSMCs play key roles in accelerating atherosclerosis. In this study, by utilizing the significant advantages of nano-materials, a biomimetic nanoliposome loading with Evolocumab (Evol), a PCSK9 inhibitor, was designed to alleviate atherosclerosis. In vitro results showed that (Lipo + M)@E NPs up-regulated the levels of α-SMA and Vimentin, while inhibiting the expression of OPN, which finally result in the inhibition of the phenotypic transition, excessive proliferation, and migration of VSMCs. In addition, the long circulation, excellent targeting, and accumulation performance of (Lipo + M)@E NPs significantly decreased the expression of PCSK9 in serum and VSMCs within the plaque of ApoE-/- mice.
Assuntos
Aterosclerose , Pró-Proteína Convertase 9 , Camundongos , Animais , Pró-Proteína Convertase 9/metabolismo , Lipossomos , Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismoRESUMO
Dioscoreae hypoglaucae Rhizoma (DH) and Dioscoreae spongiosae Rhizoma (DS) are two similar Chinese herbal medicines derived from the Dioscorea family. DH and DS have been used as medicines in China and other Asian countries for a long time, but study on their phytochemicals and bioactive composition is limited. This present study aimed to compare the chemical compositions of DH and DS, and explore the anti-xanthine oxidase components based on chemometric analysis and spectrum-effect relationship. Firstly, an HPLC method was used to establish the chemical fingerprints of DH and DS samples, and nine common peaks were selected. Then, hierarchical clustering analysis, principal component analysis and orthogonal partial least squares discriminant analysis were employed to compare and discriminate DH and DS samples based on the fingerprints data, and four steroidal saponins compounds (protodioscin, protogracillin, dioscin, gracillin) could be chemical markers responsible for the differences between DH and DS. Meanwhile, the anti-xanthine oxidase activities of these two herbal medicines were evaluated by xanthine oxidase inhibitory assay in vitro. Pearson correlation analysis and partial least squares regression analysis were subsequently used to investigate the spectrum-effect relationship between chemical fingerprints and xanthine oxidase inhibitory activities. The results showed that four steroidal saponins, including protodioscin, protogracillin, methyl protodioscin and pseudoprogracillin could be potential anti-xanthine oxidase compounds in DH and DS. Furthermore, the xanthine oxidase inhibitory activities of the four selected inhibitors were validated by anti-xanthine oxidase inhibitory assessment and molecular docking experiments. The present work provided evidence for understanding of the chemical differences and the discovery of the anti-xanthine oxidase constituent of DH and DS, which could be useful for quality evaluation and bioactive components screening of these two herbal medicines.
Assuntos
Medicamentos de Ervas Chinesas , Plantas Medicinais , Saponinas , Xantina Oxidase , Quimiometria , Simulação de Acoplamento Molecular , Medicamentos de Ervas Chinesas/química , Saponinas/farmacologia , Cromatografia Líquida de Alta PressãoRESUMO
A GaInAsP/GaAs/GaAsP Al-free laser with asymmetric potential barriers is designed theoretically to prevent carrier leakage. The band alignment demonstrates that a high height of the potential barrier decreases the leakage current. The internal quantum efficiency increases by increasing the injection efficiency, which is attributed to the decreasing electron potential barrier heights. Moreover, the threshold current and operating voltage decrease by adopting a novel barrier so that the output power and power conversion efficiency (PCE) increase. When the injection current is 5â kA/cm2, the PCE is 77.82% and the output power is 13.21 W. The physical mechanism of potential barrier heights affecting carrier transport is investigated, which will provide a theoretical basis for optimizing laser diodes.
RESUMO
Phosphogypsum is a by-product of phosphoric acid production by a wet-process and can be used to prepare adsorption materials to treat Cd(II) in sewage. Its main component is calcium sulfate dihydrate (gypsum). In the present study, incorporation and adsorption of cadmium on gypsum in an aqueous environment have been investigated using dispersion-corrected density functional theory, and the effect of different vacancy defects on the adsorption and doping of Cd on gypsum was also studied. The results show that Cd impurity defects can form more easily in gypsum crystals with Ca vacancy defects. The increase in both calcium vacancy defects and sulfate vacancy defects is beneficial to the incorporation of Cd in calcium sulfate dihydrate. In addition, the calcium vacancy defects on the gypsum surface can promote the adsorption of Cd(II), while sulfate vacancy defects on the gypsum surface inhibit the adsorption of Cd(II). Therefore, increasing the Ca vacancy defects of gypsum will help in improving the adsorption and curing properties of phosphogypsum for cadmium.
RESUMO
The gut microbiota forms a complex microecosystem in vertebrates and is affected by various factors. As a key intrinsic factor, sex has a persistent impact on the formation and development of gut microbiota. Few studies have analyzed sexual dimorphism of gut microbiota, particularly in wild animals. We used 16S rRNA gene sequencing to analyze the gut microbiota of juvenile and adult Chinese alligators, and untargeted metabolomics to study serum metabolomes of adult alligators. We observed significant sexual differences in the community diversity in juvenile, but not adult, alligators. In terms of taxonomic composition, the phylum Fusobacteriota and genus Cetobacterium were highly abundant in adult alligators, similar to those present in carnivorous fishes, whereas the gut microbiota composition in juvenile alligators resembled that in terrestrial reptiles, indicating that adults are affected by their wild aquatic environment and lack sex dimorphism in gut microbiota. The correlation analysis revealed that the gut microbiota of adults was also affected by cyanobacteria in the external environment, and this effect was sex-biased and mediated by sex hormones. Overall, this study reveals sexual differences in the gut microbiota of crocodilians and their convergence in the external environment, while also providing insights into host-microbiota interactions in wildlife.
Assuntos
Jacarés e Crocodilos , Microbioma Gastrointestinal , Animais , Caracteres Sexuais , RNA Ribossômico 16S/genética , Fator Intrínseco , Hormônios Esteroides Gonadais , ChinaRESUMO
RATIONALE: 3-Monochloropropane-1,2-diol (3-MCPD) is a well-known contaminant formed in food thermal processing, which could be found in a variety of foodstuffs. Due to its potential carcinogenicity, it was essential to quickly develop a rapid and high-throughput analytical method to monitor 3-MCPD in foodstuffs, which is described in this study. METHODS: 3-MCPD was extracted from foodstuffs and then was derivatized with a boronic acid-modified C60 (B-C60 ) through the boronic acid-diol reaction. Microwave heating was used to accelerate the derivatization reaction. Mass spectrometry (MS) analysis was conducted using matrix-assisted laser desorption/ionization-MS (MALDI-MS). The application of the method was validated using various smoked food samples. RESULTS: The chemical derivatization of 3-MCPD with B-C60 enabled the addition of a C60 -tag to 3-MCPD. High-throughput analysis of the sample within 0.5 h was realized. A good linear range from 0.02 to 1.5 µg mL-1 for 3-MCPD was obtained, with a detection limit of 0.005 µg mL-1 . The recoveries in spiked foodstuffs ranged from 85.4% to 115.1% with relative standard deviations of 2.0%-14.2%. This method was successfully applied to detect 3-MCPD in smoked foodstuffs. CONCLUSIONS: A quantitative method was developed for the detection of 3-MCPD in foodstuffs using B-C60 derivatization combined with MALDI-MS strategy. This proposed method may serve as a potential platform for the rapid and high-throughput analysis of 3-MCPD in foodstuffs for the purpose of food safety control.
Assuntos
Carne/análise , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , alfa-Cloridrina/química , Animais , Ácidos Borônicos/química , Culinária , Peixes , Contaminação de Alimentos/análise , SuínosRESUMO
Protein phosphorylation is a crucial posttranslational modification for the regulation of many different biological functions. Selective enrichment of phosphopeptides from the complex biological samples is an essential step for the mass spectrometry analysis of protein phosphorylation. In this study, an arsenate functionalized monolithic column was first prepared by a single-step copolymerization of p-methacryloylaminophenylarsonic acid and ethylene dimethacrylate. Then the metal ions Zr4+ were attached onto the prepared monolithic column via metal-chelate complex formation by Zr4+ and arsenate groups. The obtained monolithic column was employed as a new sorbent for the phosphopeptide enrichment via immobilized metal affinity chromatography. Phosphopeptides analysis was realized by polymer monolith microextraction using this monolithic column coupled to both matrix-assisted laser desorption/ionization mass spectrometry and liquid chromatography-electrospray ionization tandem mass spectrometry. The proposed method exhibited a high selectivity for phosphopeptide enrichment in complex matrices, and was applied to the analysis of phosphopeptides in human serum and tryptic digests of rat brain proteins. Four phosphopeptides could be selectively captured from human serum and 2608 endogenous phosphopeptides were identified from the tryptic digests of rat brain proteins, indicating a satisfactory performance of this method for the enrichment of phosphopeptides from complex biological samples.
Assuntos
Arseniatos/química , Fosfopeptídeos/isolamento & purificação , Zircônio/química , Adsorção , Animais , Encéfalo/metabolismo , Humanos , Tamanho da Partícula , Fosfopeptídeos/sangue , Fosfopeptídeos/química , Proteínas/química , Proteínas/metabolismo , Ratos , Propriedades de SuperfícieRESUMO
Here, it reports a high-throughput detection method for reliably quantitative analysis of illegal drugs in complex biological samples by means of a surface-enhanced Raman scattering (SERS) active microcavity and rapid pretreatment device. Based on the well-made hemispherical microcavities that regularly distributed on a glass array, the quality-controllable microcavity device is fabricated by the compact self-assembly of core-shell nanopeanuts (CSNPs) onto the inside surface. Both the CSNPs with a quantifiable internal standard signal of crystal violet acetate anchored inside their gap and the well-made microcavity referred to the physical amplification of the microscale groove surface will do well in trace analysis, which will allow us to realize the accurately quantitative SERS analysis of targeted analytes spread on the bottom area of the microcavity array. As an example, 0.8 nM malachite green and 160 ppb methamphetamine (MATM) have been successively detected in a wide range as standard, while even 0.01 ppm MATM mixed in the urine/serum samples has been efficiently tested by the microcavity device equipped with a rapid pretreatment device (manual monolithic column syringe needle). All of the above suggest that the SERS-active microcavity equipped with a rapid pretreatment device has potential in the on-site quick test of trace amounts of illegal drugs in bodily fluid samples or other field analysis of food sanitation, environmental safety, and public health.
Assuntos
Metanfetamina/sangue , Metanfetamina/urina , Ouro/química , Humanos , Nanopartículas Metálicas/química , Análise Espectral Raman , Propriedades de SuperfícieRESUMO
BACKGROUND: In China, the incidence of cancer has significantly decreased over the last two decades. In contrast, the incidence of gastric carcinoma (GC) has risen in young patients. METHODS: We reevaluated the histopathological results of 4,353 endoscopic gastroscopies from the Department of Pathology at No 1 Hospital of Liangshan. The ethnic groups Han and Yi were almost equally distributed in this cohort. Over a five-year period, 1407 GC were diagnosed. RESULTS: In 171 of these cases (12%), the patients were ≤40 years old (early-onset GC, EOGC). Out of this cohort, 9 patients were aged ≤25 years. 54% of these patients were male and showed marked predominance (92%) of the Yi-minority. Using the classification of Lauren, 103 GC (60%) were of diffuse type, 27 (16%) of intestinal type, and 41 (24%) of mixed type. In the remaining 1,236 cases of patients ≥41 years (88%), 1,014 patients (82%) belonged to the Yi-minority. Helicobacter pylori (HP) were found in 46% of all cases. Familial clustering was found in 14 patients (18%; in first degree relatives, 12%, and in second degree relatives, 6%). Follow-up was not possible. CONCLUSION: This study demonstrates the unequal manifestation of EOGC within the two ethnic groups of Han and Yi. However, familial clustering was infrequent. Further investigations are necessary to discover relevant risk factors apart from hereditary predisposition.
Assuntos
Neoplasias Gástricas/epidemiologia , Adolescente , Adulto , Idade de Início , Idoso , Biópsia , China/epidemiologia , Detecção Precoce de Câncer , Feminino , Gastroscopia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prevalência , Vigilância em Saúde Pública , Neoplasias Gástricas/patologia , Adulto JovemRESUMO
The ecological planting of Chinese medicinal materials is a cultivation technology that takes into account both ecological and economic benefits, and takes scientific planting technology as a guide to achieve the goal of high quality, high yield and efficiency of Chinese medicinal materials and the sustainable and healthy development of Chinese medicinal materials planting. Among them, scientific fertilization is an important measure to realize the ecological planting of Chinese medicinal materials. In recent years, the social economy has developed rapidly. In the production of Chinese herbal medicines, a large amount of chemical fertilizers and pesticides have been gradually used to increase short-term economic benefits. The unreasonable use of chemical fertilizers and pesticides has neglected the output, quality, safety, environmental pollution and environmental protection of medicinal materials. The impact of continuous development. Therefore, from the perspective of research on cultivation of Chinese medicinal materials, this article briefly describes the role and measures of scientific fertilization in ecological planting of Chinese medicinal materials. The roles of scientific fertilization in solving soil pollution and soil quality deterioration of Chinese herbal medicine cultivation, sustainable deve-lopment of Chinese herbal medicine production, unstable production quality of Chinese herbal medicine products, and quality safety are summarized separately. It is proposed measures based on the characteristics of soil fertilization, the growth and development characteristics of Chinese medicinal materials as the core, and the industrial planting model as the carrier to promote scientific fertilization in the cultivation of Chinese medicinal materials. Finally, the development direction of scientific fertilization and ecological plan-ting of traditional Chinese medicine is prospected, in order to provide support and reference for the development of ecological planting of traditional Chinese medicine.
Assuntos
Medicamentos de Ervas Chinesas , Plantas Medicinais , Povo Asiático , China , Fertilização , Humanos , Medicina Tradicional ChinesaRESUMO
In recent years, the concept of treatment after surgery in the department of orthopedics has changed from hemostasis to anticoagulant. This article analyses the safety and effectiveness of anticoagulants for prophylactic anticoagulants after spinal fractures. By analyzing the incidence of bleeding and VTE in 2 weeks after operation, there was no significant difference between the 2 groups (P>0.05), but the incidence of VTE in rivaroxaban group was significantly lower than that in control group. In conclusion, the rivaroxaban oral anticoagulants are stable, safe and easy to use. It significantly reduced the incidence of VTE after spinal fracture and nerve injury, and did not increase the risk of bleeding. It is an ideal type of prophylactic anticoagulant after the operation of spinal fracture, which is worthy of further clinical study.
Assuntos
Fixação Interna de Fraturas/efeitos adversos , Rivaroxabana/uso terapêutico , Fraturas da Coluna Vertebral/cirurgia , Trombose/etiologia , Humanos , Complicações Pós-Operatórias , Estudos Retrospectivos , Trombose/prevenção & controleRESUMO
BACKGROUND Acid-sensing ion channels (ASICs) are ligand-gated cation channels activated by extracellular protons. However, the role of ASICs in kidney diseases remains uncertain. This study investigated ASICs expression in kidney tissues and their role in the development of Henoch-Schönlein purpura nephritis (HSPN). MATERIAL AND METHODS The expression of ASIC subunits was examined by immunochemical techniques in the kidney tissue from HSPN patients. Acid-induced ASICs expression in cultured renal tubular epithelial cells was determined by quantitative RT-PCR analysis. The expression of K7 and K18 protein in renal tubular epithelial cells was used to evaluate acid-induced cell injury. In addition, we observed the effect of blocking ASICs on acid-induced cell injury to assess the role of ASICs in renal tubular epithelial cell injury. RESULTS The results showed that ASIC1, ASIC2, and ASIC3 proteins were obviously expressed in renal tubular cells from HSPN patients. ASIC1 expression and 24-h urine protein level were higher in the pathological grade ISKD III group than in the ISKD II group. ASIC1, ASIC2, and ASIC3 mRNA, and K7 and K18 protein expression in cultured renal tubular epithelial cells were increased when exposed to pH 6.5. K7 and K18 protein expression was closely related to ASIC1 expression, and ASICs blockers reduced K7 and K18 protein expression in tubular epithelial cells. CONCLUSIONS These findings suggest ASICs are most highly expressed in renal tubular cells of HSPN patients, which is closely related to renal tubular injury. ASICs might be involved in the development of HSPN.
Assuntos
Canais Iônicos Sensíveis a Ácido/genética , Canais Iônicos Sensíveis a Ácido/metabolismo , Vasculite por IgA/metabolismo , Adolescente , Adulto , Criança , Células Epiteliais/metabolismo , Feminino , Glomerulonefrite/metabolismo , Humanos , Vasculite por IgA/genética , Rim/patologia , Túbulos Renais/metabolismo , Masculino , Nefrite/genética , Nefrite/metabolismo , RNA Mensageiro/metabolismoRESUMO
The bluetongue virus (BTV) NS1 protein is one of the major proteins synthesized during BTV infection and is responsible for the generation of virus-specific tubules. Although some functional and structural studies on the BTV NS1 protein have been reported, there have been no reports describing the linear B-cell epitopes recognized by humoral immune responses published to date. In this study, 25 BTV12 NS1-reactive monoclonal antibodies (MAbs) and polyclonal antisera (polyclonal antibodies, PAbs) were generated and analyzed. We identified 14 linear NS1 epitopes recognized by the PAbs and MAbs using NS1-derived peptides in an enzyme-linked immunosorbent assay. Moreover, we predicted 23 linear B-cell epitopes using the ABCpred online server which employs an artificial neural network. Analysis of the predicted and identified epitopes of NS1 demonstrated the feasibility of B-cell epitope prediction. Sequence alignments indicated that the epitopes recognized by MAbs are highly conserved among BTV serotypes, but not among the other members of the genus Orbivirus, such as the African horse sickness virus (AHSV), epizootic hemorrhagic disease virus (EHDV), and Chuzan disease virus (CV). Importantly, we identified specific MAbs that recognized all BTV serotypes tested as well as MAbs that recognized only BTV12, suggesting that these NS1-specific MAbs could serve as a basis for BTV diagnostic approaches. The generation and identification of NS1 protein epitopes will provide the foundation for further studies about the function and structure of NS1 and novel epitope-based vaccines.
Assuntos
Vírus Bluetongue/imunologia , Bluetongue/virologia , Epitopos de Linfócito B/química , Proteínas não Estruturais Virais/química , Sequência de Aminoácidos , Animais , Anticorpos/análise , Anticorpos/imunologia , Vírus Bluetongue/química , Vírus Bluetongue/genética , Linhagem Celular , Cricetinae , Mapeamento de Epitopos , Epitopos de Linfócito B/genética , Epitopos de Linfócito B/imunologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Dados de Sequência Molecular , Alinhamento de Sequência , Proteínas não Estruturais Virais/genética , Proteínas não Estruturais Virais/imunologiaRESUMO
OBJECTIVE: It had been shown that apoptosis of vascular endothelial cells played an important role in the pathogenesis of HSP. The present study was designed to investigate the apoptosis of vascular endothelial cells induced by isolated IgA1 from sera of HSP patients. METHODS: HUVEC were cultured in 3 different types of media with IgA1 from HSP patients, normal healthy children and simply medium (blank control). Serum IgA1 was purified by jacalin affinity chromatography. The rates of apoptosis in HUVEC incubated with IgA1 were determined by the TUNEL method and flow cytometry, respectively. The expression of bax/bcl-2 and p53 was detected with the methods of Real-time PCR and Westernblot, respectively. RESULT: The results showed that the apoptosis rate of HUVEC by IgA1 isolated from HSP patients was higher than that the normal controls (14.77±2.23% vs 9.97±1.48%) and blank controls (14.77±2.23% vs 2.25±0.77%) (P <0.01). Moreover the rate of HUVEC by IgA1 from normal healthy children was higher than the blank controls (9.97±1.48% vs 2.25±0.77%) (P <0.01). In addition, the bax and P53 expression were up-regulated and the Bcl-2 expression was down-regulated in HUVEC co-cultured with IgA1 isolated from HSP patients for 24 hours. CONCLUSIONS: These findings suggested that IgA1 from HSP patients could induce the apoptosis of HUVEC, which might be related to the vascular endothelial injury of HSP.
Assuntos
Apoptose/imunologia , Células Endoteliais da Veia Umbilical Humana/imunologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Vasculite por IgA/imunologia , Imunoglobulina A/imunologia , Adolescente , Apoptose/genética , Células Cultivadas , Criança , Feminino , Humanos , Vasculite por IgA/sangue , Imunoglobulina A/sangue , Masculino , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-2/imunologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/imunologia , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/imunologiaRESUMO
BACKGROUND: In humans, Alzheimer's disease (AD) is typically sporadic in nature, and its pathology is usually influenced by extensive factors. The study established a rat model based on the genetic-environmental interaction. METHODS: A rat model was established by transduction of an adeno-associated virus combined with acrolein treatment. Rats were assigned to the normal control (NC), acrolein group, AAV (-) group, AAV-APP group, and AAV-APP/acrolein group. The success of model construction was verified in multiple ways, including by assessing cognitive function, examining microstructural changes in the brain in vivo, and performing immunohistochemistry. The contribution of genetic (APP mutation) and environmental (acrolein) factors to AD-like phenotypes in the model was explored by factorial analysis. RESULTS: 1) The AAV-APP/acrolein group showed a decline in cognitive function, as indicated by a reduced gray matter volume in key cognition-related brain areas, lower FA values in the hippocampus and internal olfactory cortex, and Aß deposition in the cortex and hippocampus. 2) The AAV-APP group also showed a decline in cognitive function, although the group exhibited atypical brain atrophy in the gray matter and insignificant Aß deposition. 3) The acrolein group did not show any significant changes in Aß levels, gray matter volume, or cognitive function. 4) The genetic factor (APP mutation) explained 39.74% of the AD-like phenotypes in the model factors, and the environmental factor (acrolein exposure) explained 33.3%. CONCLUSIONS: The genetic-environmental interaction rat model exhibited a phenotype that resembled the features of human AD and will be useful for research on AD.
Assuntos
Doença de Alzheimer , Transtornos Cognitivos , Humanos , Ratos , Animais , Camundongos , Doença de Alzheimer/patologia , Precursor de Proteína beta-Amiloide/metabolismo , Acroleína , Encéfalo/metabolismo , Peptídeos beta-Amiloides/metabolismo , Modelos Animais de Doenças , Camundongos TransgênicosRESUMO
OBJECTIVE: To investigate the effect of Ganoderma Lucidum Spore Oil (GLSO) on the tumor growth and survival of H22 tumor-bearing mice treated with cyclophosphamide (CTX), and explore the underlying mechanism. METHODS: Allograft H22 hepatocellular carcinoma mouse model was applied to investigate the effect of GLSO on the tumor growth and survival of animals, and Kaplan-Meier survival analysis was used to analyze the life span. Plasma biochemical examination was used to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea (UREA) and creatinine (CRE). Western blot analysis was performed to detect Programmed Death-1 (PD-1), Programmed Death Ligand 1 (PD-L1), Janus Kinase 2 (JAK2), phosphorylated Signal Transducer and Activator of Transcription 3 (p-STAT3), and Signal Transducer and Activator of Transcription 3 (STAT3) expression. RESULTS: GLSO increased the anti-tumor effect of CTX and prolonged the survival of H22 tumor-bearing mice treated with CTX. Meanwhile, GLSO increased the thymus index and showed no obvious toxicity to liver functions of animals. GLSO also decreased the level of UREA in H22 tumor-bearing mice treated with CTX. Furthermore, GLSO could inhibit the expression of PD-1 in spleen, which was independent of JAK2 expression and STAT3 phosphorylation. However, GLSO did not affect the expression of PD-L1, JAK2, and p-STAT3 in tumor tissue. CONCLUSION: GLSO could strengthen the anti-tumor effect of CTX and prolong the life span of H22 tumor-bearing mice, while the underlying mechanism might be relevant to the amelioration effect of thymus function and inhibition of PD-1 expression in spleen. Furthermore, these findings implied the promising role of GLSO in combination with CTX to extend the survival of patients in clinical chemotherapy of hepatocellular carcinoma.
Assuntos
Ciclofosfamida , Neoplasias Hepáticas , Receptor de Morte Celular Programada 1 , Animais , Humanos , Masculino , Camundongos , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Linhagem Celular Tumoral , Ciclofosfamida/efeitos adversos , Medicamentos de Ervas Chinesas/administração & dosagem , Janus Quinase 2/metabolismo , Janus Quinase 2/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/genética , Fator de Transcrição STAT3/metabolismo , Fator de Transcrição STAT3/genéticaRESUMO
BACKGROUND: With the development of percutaneous coronary intervention (PCI), the number of interventional procedures without implantation, such as bioresorbable stents (BRS) and drug-coated balloons, has increased annually. Metal drug-eluting stent unloading is one of the most common clinical complications. Comparatively, BRS detachment is more concealed and harmful, but has yet to be reported in clinical research. In this study, we report a case of BRS unloading and successful rescue. CASE SUMMARY: This is a case of a 59-year-old male with the following medical history: "Type 2 diabetes mellitus" for 2 years, maintained with metformin extended-release tablets, 1 g PO BID; "hypertension" for 20 years, with long-term use of metoprolol sustained-release tablets, 47.5 mg PO QD; "hyperlipidemia" for 20 years, without regular medication. He was admitted to the emergency department of our hospital due to intermittent chest pain lasting 18 hours, on February 20, 2022 at 15: 35. Electrocardiogram results showed sinus rhythm, ST-segment elevation in leads I and avL, and poor R-wave progression in leads V1-3. High-sensitivity troponin I level was 4.59 ng/mL, indicating an acute high lateral wall myocardial infarction. The patient's family requested treatment with BRS, without implantation. During PCI, the BRS became unloaded but was successfully rescued. The patient was followed up for 2 years; he had no episodes of angina pectoris and was in generally good condition. CONCLUSION: We describe a case of a 59-year-old male experienced BRS unloading and successful rescue. By analyzing images, the causes of BRS unloading and the treatment plan are discussed to provide insights for BRS release operations. We discuss preventive measures for BRS unloading.
RESUMO
Crocodile meat is a novel reptile meat source, but its processing method is rare. This study investigated the effect of κ-carrageenan addition and partial substitution of NaCl on the gel properties of crocodile myofibrillar protein (CMP). Result showed that CMP formed gel when temperature above 60 â. The water-holding capacity, gel strength, denaturation degree, sulfhydryl content covalent bond and hydrophobic bond of gel in KCl solution were significantly higher than those in CaCl2 solution (Pâ¯<â¯0.05). K+ induced CMP to form a tight network structure with uniform small pores though covalent and hydrophobic bonds, but the gel properties were reduced by κ-carrageenan. In CaCl2 solution, κ-carrageenan improved the gel structure by filling the protein network through hydrogen bonding. Therefore, it can be concluded that KCl is better than CaCl2 in the manufacturing of low-sodium crocodile foods. Moreover, κ-carrageenan was only beneficial to gel quality in CaCl2 solution.