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Recycling silicon cutting waste (SCW) plays a pivotal role in reducing environmental impact and enhancing resource efficiency within the semiconductor industry. Herein SCW was utilized to prepare SiC and ultrasound-assisted leaching was investigated to purify the obtained SiC and the leaching factors were optimized. The mixed acids of HF/H2SO4 works efficiently on the removal of Fe and SiO2 due to that HF can react with SiO2 and Si and then expose the Fe to H+. The assistance of ultrasound can greatly improve the leaching of Fe, accelerate the leaching rate, and lower the leaching temperature. The optimal leaching conditions are HF-H2SO4 ratio of 1:3, acid concentration of 3 mol/L, temperature of 50 °C, ultrasonic frequency of 45 kHz and power of 210 W, and stirring speed of 300 rpm. The optimal leaching ratio of Fe is 99.38%. Kinetic analysis shows that the leaching process fits the chemical reaction-controlled model.
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Reciclagem , Silício , Silício/química , Compostos de Silício/química , Compostos Inorgânicos de Carbono/química , Dióxido de Silício/química , Cinética , TemperaturaRESUMO
OBJECTIVES: Using a random forest algorithm, we previously found that teicoplanin-associated gene A (tcaA) might play a role in resistance of methicillin-resistant Staphylococcus aureus (MRSA) to ß-lactams, which we have investigated further here. METHODS: Representative MRSA strains of prevalent clones were selected to identify the role of tcaA in the MRSA response to ß-lactams. tcaA genes were deleted by homologous recombination in the selected MRSA strains, and antibiotic susceptibility tests were applied to evaluate the effect of tcaA on the minimum inhibitory concentrations (MICs) of glycopeptides and ß-lactams. Scanning electron microscopy, RNA sequencing, and quantitative reverse transcription-polymerase chain reaction were performed to explore the mechanism of tcaA in MRSA resistance to ß-lactams. RESULTS: The MIC of penicillin plus clavulanate decreased from 3 mg/L to 0.064 mg/L and that of oxacillin decreased from 16 to 0.5 mg/L when tcaA was knocked out in the LAC strain. Compared with wild-type MRSA isolates, when tcaA was deleted, all selected strains were more susceptible to ß-lactams. Susceptibility to ceftobiprole was restored in the ceftobiprole-resistant strain when tcaA was deleted. tcaA knockout caused "log-like" abnormal division of MRSA, and tcaA deficiency mediated low expression of mecA, ponA, and murA2. CONCLUSIONS: Machine learning is a reliable tool for identifying drug resistance-related genes. tcaA may be involved in S. aureus cell division and may affect mecA, ponA, and murA2 expression. Furthermore, tcaA is a potential resistance breaker target for ß-lactams, including ceftobiprole, in MRSA.
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Antibacterianos , Cefalosporinas , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Resistência beta-Lactâmica , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Antibacterianos/farmacologia , Cefalosporinas/farmacologia , Humanos , Resistência beta-Lactâmica/genética , Proteínas de Bactérias/genética , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/tratamento farmacológico , beta-Lactamas/farmacologia , Técnicas de Inativação de GenesRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Non-alcoholic steatohepatitis (NASH) is a common metabolic liver injury disease that is closely associated with obesity and metabolic disorders. Paeonol, an active ingredient found in Moutan Cortex, a traditional Chinese medicine which exhibits significant therapeutic effect on liver protection, has shown promising effects in treating liver diseases, particularly NASH. However, the specific intervention mechanism of paeonol on NASH is still unknown. AIM OF THE STUDY: Our objective is to elucidate the pharmacological mechanism of paeonol in intervening NASH at the in vivo level, focusing on the impact on intestinal flora, tryptophan-related targeted metabolome, and related Aryl hydrocarbon receptor (AhR) pathways. MATERIALS AND METHODS: Here, we explored the intervention effect of paeonol on NASH by utilizing the NASH mouse model. The Illumina highthroughput sequencing technology was preformed to determine the differences of gut microbiota of model and paeonol treatment group. The concentration of Indoleacetic acid is determined by ELISA. The intervention effect of NASH mouse and AhR/NLRP3/Caspase-1 metabolic pathway is analyzed by HE staining, oil red O staining, Immunohistochemistry, Immunofluorescence, Western blot and qRT-PCR assays. Fecal microbiota transplantation experiment also was performed to verify the intervention effect of paeonol on NASH by affecting gut microbiota. RESULTS: Firstly, we discovered that paeonol effectively reduced liver pathology and blood lipid levels in NASH mice, thereby intervening in the progression of NASH. Subsequently, through 16S meta-analysis, we identified that paeonol can effectively regulate the composition of intestinal flora in NASH mice, transforming it to resemble that of normal mice. Specifically, paeonol decreased the abundance of certain Gram-negative tryptophan-metabolizing bacteria. Moreover, we discovered that paeonol significantly increased the levels of metabolites Indoleacetic acid, subsequently enhancing the expression of AhR-related pathway proteins. This led to the inhibition of the NOD-like receptor protein 3 (NLRP3) inflammasome production and inflammation generation in NASH. Lastly, we verified the efficacy of paeonol in intervening NASH by conducting fecal microbiota transplantation experiments, which confirmed its role in promoting the AhR/NLRP3/cysteinyl aspartate specific proteinase (Caspase-1) pathway. CONCLUSIONS: Our findings suggest that paeonol can increase the production of Indoleacetic acid by regulating the gut flora, and promote the AhR/NLRP3/Caspase-1 metabolic pathway to intervene NASH.
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Acetofenonas , Caspase 1 , Microbioma Gastrointestinal , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR , Hepatopatia Gordurosa não Alcoólica , Receptores de Hidrocarboneto Arílico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Animais , Acetofenonas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Masculino , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptores de Hidrocarboneto Arílico/metabolismo , Caspase 1/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Modelos Animais de Doenças , Fígado/efeitos dos fármacos , Fígado/metabolismo , Transdução de Sinais/efeitos dos fármacos , Redes e Vias Metabólicas/efeitos dos fármacosRESUMO
OBJECTIVES: Fosfomycin has regained attention for treating infections caused by methicillin-resistant Staphylococcus aureus and multidrug-resistant coagulase-negative staphylococci. In this research, our objective was to investigate the mechanisms underlying fosfomycin resistance in Staphylococcus capitis. METHODS: The minimum inhibitory concentrations (MICs) of fosfomycin were assessed in 109 clinical S. capitis isolates by the agar dilution method. By cloning the fos-like genes into the shuttle vector, pTSSCm-Pcap, and observing the change in fosfomycin MICs, the gene function was verified. Core genome multilocus sequence typing and comparative genomics analysis were conducted to determine the population characteristics of S. capitis isolates and analyse the genetic environment of the fos-like genes. RESULTS: We identified a novel fosfomycin resistance gene, fosSC, on the chromosome in 58 out of 109 (53.2%) S. capitis isolates. The deduced products of the fosSC genes shared 67.15-67.88% amino acid sequence identity with FosB. The RN-pT-fosSC transformants carrying fosSC showed a 512-fold increase in the fosfomycin MICs. The fosSC gene was embedded in a conserved genetic context, but IS431mec was located to the left of the fosSC gene in cluster L due to the insertion of staphylococcal cassette chromosome mec. CONCLUSIONS: The chromosomal fosSC genes in some lineages of S. capitis explained their high-level fosfomycin resistance. Ongoing surveillance is crucial for monitoring the potential threat of horizontal transfer, which could be facilitated by the presence of mobile genetic elements surrounding the fosSC gene.
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Antibacterianos , Farmacorresistência Bacteriana , Fosfomicina , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas , Staphylococcus capitis , Fosfomicina/farmacologia , Antibacterianos/farmacologia , Humanos , Infecções Estafilocócicas/microbiologia , Staphylococcus capitis/genética , Staphylococcus capitis/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Tipagem de Sequências Multilocus , Genes Bacterianos/genéticaAssuntos
Daptomicina , Desinfetantes , Resistência Microbiana a Medicamentos , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Daptomicina/farmacologia , Desinfetantes/farmacologia , Staphylococcus aureus Resistente à Meticilina/genética , Testes de Sensibilidade Microbiana , Mutação , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Resistência Microbiana a Medicamentos/genéticaRESUMO
Background and rationale: Attenuated Salmonella typhimurium VNP20009 has been used to treat tumor-bearing mice and entered phase I clinical trials. However, its mild anticancer effect in clinical trials may be related to insufficient bacterial colonization and notable adverse effects with increasing dosages. Guanosine 5'-diphosphate-3'-diphosphate (ppGpp) synthesis-deficient Salmonella is an attenuated strain with good biosafety and anticancer efficacy that has been widely investigated in various solid cancers in preclinical studies. Integration of the advantages of these two strains may provide a new solution for oncolytic bacterial therapy. Methods: We incorporated the features of ΔppGpp into VNP20009 and obtained the HCS1 strain by deleting relA and spoT, and then assessed its cytotoxicity in vitro and antitumor activities in vivo. Results: In vitro experiments revealed that the invasiveness and cytotoxicity of HCS1 to cancer cells were significantly lower than those of the VNP20009. Additionally, tumor-bearing mice showed robust cancer suppression when treated with different doses of HCS1 intravenously, and the survival time and cured mice were dramatically increased. Furthermore, HCS1 can increase the levels of pro-inflammatory cytokines in tumor tissues and relieve the immunosuppression in the tumor microenvironments. It can also recruit abundant immune cells into tumor tissues, thereby increasing immune activation responses. Conclusion: The newly engineered Salmonella HCS1 strain manifests high prospects for cancer therapeutics and is a promising option for future clinical cancer immunotherapy.
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Neoplasias , Animais , Camundongos , Neoplasias/terapia , Salmonella typhimurium/genética , Imunoterapia , Microambiente TumoralRESUMO
Daptomycin (DAP) is effective against methicillin-resistant Staphylococcus aureus (MRSA). However, reduced susceptibility to DAP in MRSA may lead to treatment failures. We aim to determine the distribution of DAP minimum inhibitory concentrations (MICs) and DAP heteroresistance (hDAP) among MRSA lineages in China. A total of 472 clinical MRSA isolates collected from 2015 to 2017 in China were examined for DAP susceptibility. All isolates (n = 472) were found to be DAP susceptible, but 35.17% (166/472) of them exhibited a high DAP MIC (MIC >0.5 µg/mL). The high DAP MIC group contained a larger proportion of isolates with a higher vancomycin or teicoplanin MIC (>1.5 µg/mL) than the low DAP MIC group (19.3% vs 7.8%, P < 0.001; 22.3% vs 8.2%, P < 0.001). We compared the clonal complex (CC) distributions and clinical characteristics in MRSA isolates stratified by DAP MIC. CC5 isolates were less susceptible to DAP (MIC50 = 1 µg/mL) than CC59 isolates (MIC50 = 0.5 µg/mL, P < 0.001). Population analysis profiling revealed that 5 of 10 ST5 and ST59 DAP-susceptible MRSA isolates investigated exhibited hDAP. The results also showed that CC5 MRSA with an agrA mutation (I238K) had a higher DAP MIC than those with a wild-type agrA (P < 0.001). The agrA-I238K mutation was found to be associated with agr dysfunction as indicated by the loss of δ-hemolysin production. In addition, agr/psmα defectiveness was associated with hDAP in MRSA. Whole-genome sequencing analysis revealed mutations in mprF and walR/walK in DAP-resistant subpopulations, and most DAP-resistant subpopulations (6/8, 75%) were stable. Our study suggests that the increased DAP resistance and hDAP in MRSA may threaten the effectiveness against MRSA infections.
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Daptomicina , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Daptomicina/farmacologia , Daptomicina/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Vancomicina/farmacologia , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: Accumulating evidence suggested increasing energy expenditure is a feasible strategy for combating obesity, and browning of white adipose tissue (WAT) to promote thermogenesis might be one of the attractive ways. Hydroxy-α-sanshool (HAS), a natural amide alkaloid extracted from the fruits of Zanthoxylum bungeanum Maxim, possesses lots of benefits in lipid metabolism regulation. METHODS: The anti-obesity effect of HAS was investigated by establishing an animal model of obesity and a 3T3-L1 differentiation cell model. Effects of HAS on the whole-body fat and liver of obese mice, and the role of HAS in inducing browning of white fat were studied by Micro CT, Metabolic cage detection, Cell mitochondrial pressure detection, transmission electron microscopy and cold exposure assays. Furthermore, the Real-time PCR (qPCR), digital PCR (dPCR), western blot, Co-immunoprecipitation (Co-IP), molecular docking, drug affinity responsive target stability (DARTS), Cellular thermal shift assay (CETSA) and other methods were used to investigate the target and mechanisms of HAS. RESULTS: We found that treatment with HAS helped mice combat obesity caused by a high fat diet (HFD) and improve metabolic characteristics. In addition, our results suggested that the anti-obesity effect of HAS is related to increase energy consumption and thermogenesis via induction of browning of WAT. The further investigations uncovered that HAS can up-regulate UCP-1 expression, increase mitochondria number, and elevate the cellular oxygen consumption rates (OCRs) of white adipocytes. Importantly, the results indicated that browning effects of HAS is closely associated with SIRT1-dependent PPAR-γ deacetylation through activating the TRPV1/AMPK pathway, and TRPV1 is the potential drug target of HAS for the browning effects of WAT. CONCLUSIONS: Our results suggested the HAS can promote browning of WAT via regulating AMPK/SIRT-1/PPARγ signaling, and the potential drug target of HAS is the membrane receptor of TRPV1.
Assuntos
PPAR gama , Zanthoxylum , Camundongos , Animais , PPAR gama/metabolismo , Frutas , Simulação de Acoplamento Molecular , Proteínas Quinases Ativadas por AMP/metabolismo , Tecido Adiposo Branco , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Alcamidas Poli-Insaturadas/farmacologia , Dieta Hiperlipídica/efeitos adversos , Células 3T3-L1 , Canais de Cátion TRPV/metabolismo , Canais de Cátion TRPV/farmacologiaRESUMO
Background: The aim of this study was to summarize the valuable information for qualitative diagnosis by investigating the imaging signs from the whole-body bone imaging of solitary rib lesions. Methods: A retrospective analysis was conducted of the data from 313 patients with malignant tumors and solitary rib lesions identified using whole-body bone imaging in Department of Nuclear Medicine of Central South University Xiangya School Affiliated Haikou Hospital between January 2015 and December 2017. Based on the final comprehensive diagnosis of the rib lesions, the patients were divided into a bone metastasis group, fracture group, other benign lesions group, and an uncertain group, and the characteristic imaging changes in rib lesions in each group were explored. Results: (I) Significant differences were identified among the 4 groups (P<0.001) in the distribution of lesions in the anterior, posterior, and lateral ribs and proximal costal cartilage. The fracture group had the highest proportion of lesions in the anterior ribs (99/121, 81.8%) and proximal costal cartilage (74.4%, 90/121). (II) Significant differences were detected in morphology, concentration, boundaries, and radioactivity distribution among the 4 groups of patients (P<0.001). The bone metastasis group had the highest proportion of lesions appearing as stripes (35/67, 52.2%), and the fracture group had the highest proportion of lesions appearing as spots (94.2%, 114/121) and the lowest proportion appearing as stripes (3/121, 2.5%). (III) Significant differences were found in the longitudinal diameter, transverse diameter, aspect ratio, and tumor-to-normal tissue ratio between the 4 groups (P<0.001). The longitudinal diameter (27.8±16.0 mm) and aspect ratio (1.9±1.0) of the bone metastasis group were the highest, whereas the longitudinal diameter (15.2±3.9 mm) and aspect ratio (1.0±0.2) of the fracture group were the smallest. Conclusions: This study revealed that different types of solitary rib lesions had relatively characteristic imaging signs in whole-body bone imaging.
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BACKGROUND: The overuse of antibiotics in livestock is contributing to the burden of antimicrobial resistance in humans, representing a One Health challenge. Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) has recently become a growing concern, and ST9 is the major LA-MRSA lineage in China and has emerged in clinical settings. METHODS: Antimicrobial susceptibility testing was used to evaluate the tetracycline resistance of ST9 MRSA collections, and gene cloning experiments were performed to explore the resistance mechanisms. Whole-genome sequencing and comparative genomics were used to analyse the genetic features of clinical ST9 isolates. A phylogenetic tree was constructed to investigate the relationship of human- and livestock-derived ST9 isolates. RESULTS: Clinical ST9 isolates were found to possess several types of resistance genes and resistance-related mutations and were multidrug-resistant. Notably, all clinical ST9 isolates were resistant to third-generation tetracyclines. Cloning experiments showed that both the acquisition of the tetracycline resistance gene tet(L)/tet(63) and a mutation in the rpsJ gene contributed to third-generation tetracycline resistance. Phylogenetic analysis showed that the ST9 isolates collected in healthcare systems were probably transmitted from livestock. The ST9 lineage underwent multiple interspecies recombination events and gained many resistance elements. Furthermore, the resistance to third-generation tetracyclines may have evolved under tetracycline pressure in livestock. CONCLUSIONS: The evolution of ST9 MRSA in livestock and transmission of this clone between humans and livestock highlight the importance of establishing control strategies with the One Health approach to reduce the burden of antibiotic resistance.
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Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Animais , Humanos , Gado , Resistência a Tetraciclina/genética , Filogenia , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/veterinária , Antibacterianos/farmacologia , Tetraciclina , China/epidemiologiaRESUMO
Benzophenone-3 (BP-3) as one of frequently used organic UV filters has been considered an emerging pollutant due to its toxicities. Benzophenone-8 (BP-8) is one of the main metabolites of BP-3 in organisms. Current reports show that BP-8 may be more toxic than BP-3. However, difference of their toxicities on embryonic development has rarely been reported. In this study, zebrafish embryos were chosen as the target organism to explore the developmental toxicities of BP-3 and BP-8. Non-targeted metabolomic analysis was performed to compare their modes of action. Results showed that BP-8 exposures led to higher bioaccumulation and lower hatching rate of zebrafish larvae than BP-3. Both BP-8 and BP-3 exposures caused behavioral abnormalities of zebrafish larvae, but no significant difference was found between them. At the metabolome level, 1 µg/L BP-3 and 1 µg/L BP-8 exposures altered neuroactive ligand-receptor interaction pathway and FoxO signaling pathway, respectively, which might be involved in the abnormal behaviors in zebrafish larvae. For higher exposure groups (30 and 300 µg/L), both BP-3 and BP-8 exposures changed metabolism of cofactors and vitamins of zebrafish larvae. Exposure of BP-3 altered the metabolism by pantothenate and CoA biosynthesis pathway, while BP-8 exposure changed riboflavin metabolism and folate biosynthesis. The above results indicated different modes of action of BP-3 and BP-8 in zebrafish embryonic development. This study sheds new light to biological hazards of BP-3 due to its metabolism in aquatic organisms.
Assuntos
Poluentes Químicos da Água , Peixe-Zebra , Animais , Peixe-Zebra/metabolismo , Protetores Solares/toxicidade , Poluentes Químicos da Água/toxicidade , Benzofenonas/toxicidadeRESUMO
BACKGROUND: Salidroside (Sal), an active component from Rhodiola crenulata, has been confirmed to exert neuroprotective effects against hypoxia. However, its molecular mechanisms of intensifying mitochondrial function still largely unknown. In the present study, we aimed to explore the mechanisms by which Sal heightened mitochondrial function in CoCl2-induced HT22 hypoxic injury. METHODS: The hypoxic condition of HT22 cells was performed by CoCl2 stimulus. We then investigated the effects of Sal on the viability of hypoxic HT22 cells by cell counting kit-8. The contents of lactate dehydrogenase (LDH) release in cultured supernatant were detected by using commercial biochemical kit. Superoxide free radical scavenging activity, total antioxidant capacity assay kit with ferric reducing ability of plasma and 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) methods were employed to detect the free radical scavenging ability and antioxidant capacity of Sal. Meanwhile, intracellular reactive oxygen species (ROS), Ca2+ and mitochondrial membrane potential (MMP) were determined by corresponding specific labeled probes. Mitochondrial morphology was tested by Mito-tracker green with confocal microscopy. Hoechst 33342 and Annexin V-FITC/propidium iodide staining were also employed to evaluate the effect of Sal on cell apoptosis. Oxygen consumption rate (OCR), real-time ATP production and proton efflux rate were measured using a Seahorse analyzer. Additionally, the potential interactions of Sal with PI3K-AKT signaling pathway-related proteins were predicted and tested by molecular docking, molecular dynamics simulation (MDS) and localized surface plasmon resonance (LSPR) techniques, respectively. Furthermore, the protein levels of p-PI3K, PI3K, p-AKT, AKT, p-JNK, JNK, p-p38 and p38 were estimated by western blot analysis. RESULTS: Sal alleviated CoCl2-induced hypoxic injury in HT22 cells as evidenced by increased cell viability and decreased LDH release. In vitro antioxidant test confirmed that Sal had marvelous antioxidant abilities. The protected mitochondrial function by Sal treatment was illustrated by the decrease of ROS, Ca2+, mitochondrial fragment and the increase of MMP. In addition, Sal ameliorated the apoptosis of HT22 cells by decreasing Hoechst 33342 positive cells and the rate of apoptotic cells. Enhancement of energy metabolism in HT22 by Sal was demonstrated by increased OCR, real-time ATP generation and proton efflux rate. The molecular docking confirmed the potential binding of Sal to PI3K, AKT and CaMK II proteins with calculated binding energy of -1.32, -4.21 and -4.38 kcal/mol, respectively. The MDS test revealed the average hydrogen bond of complex Sal-PI3K and Sal-AKT were 0.79 and 4.46, respectively. The results of LSPR verified the potential binding of Sal to proteins PI3K, AKT and HIF-1α with affinity values of 5.20 × 10 - 3, 2.83 × 10 - 3 and 3.97 × 10 - 3 KD, respectively. Western blot analysis further argued that Sal consolidated the levels of p-PI3K and p-AKT. Meanwhile, Sal could downregulate the proteins expression of p-JNK and p-p38. CONCLUSION: Collectively, our findings suggested that Sal can intensify mitochondrial function of CoCl2-simulated hypoxia injury in HT22 cells by stimulating PI3K-AKT-MAPK signaling pathway. Sal is a potential agent for mitochondrial protection against hypoxia with the underlying molecular mechanisms of energy metabolism being further elucidated.
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Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Cálcio/metabolismo , Simulação de Acoplamento Molecular , Prótons , Transdução de Sinais , Cobalto/toxicidade , Cobalto/metabolismo , Mitocôndrias/metabolismo , Hipóxia , Trifosfato de Adenosina/metabolismo , ApoptoseRESUMO
Hexafluoropropylene oxide dimer acids (HFPO-DA) and hexafluoropropylene oxide trimer acids (HFPO-TA) are alternatives to perfluorooctanoic acid (PFOA). However, little information on the comparison of their toxicities is available. Here, zebrafish embryos were exposed to PFOA, HFPO-DA, and HFPO-TA with exposure concentrations of 5 and 500 µg/L. Behavioral abnormal, enzyme activities and gene expression profiles in zebrafish embryos were determined. Results showed that exposure to PFOA and its alternatives increased heart rates and inhibited locomotor activity of zebrafish embryos. Further, their exposures changed the enzyme activities (acetylcholinesterase and oxidative stress-related enzymes), ATP content, and expressions of genes related to hypothalamic-pituitary-thyroid (HPT) axis, apoptosis, and lipid metabolism. Comparison analyses found that PFOA, HFPO-TA, and HFPO-DA exposures induced different effects on the embryonic development of zebrafish, which indicates the different modes of action. The HFPO-DA exposure induced specific effects on the disorder of lipid metabolism, HPT axis, and neurodevelopment. The HFPO-TA exposure also induced different effects from the PFOA exposure, which focused on lipid metabolism. The current data shows that the HFPO-DA and HFPO-TA might not be safe alternatives to PFOA. This study provides a new understanding of the biological hazards of PFOA alternatives in aquatic organisms, which can guide their usage.
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Fluorocarbonos , Peixe-Zebra , Animais , Óxidos , Acetilcolinesterase , Caprilatos/toxicidade , Fluorocarbonos/toxicidadeRESUMO
For thousands of years, the roots of Paeonia lactiflora Pall (PLP) has been considered by traditional Chinese medicine as a drug that can improve mental or emotional disorders, including depression, anxiety and affective disorders. Unfortunately, the research on the mechanism of action and active ingredients of this beneficial drug is not comprehensive. This study focused on the activity of essential oil from PLP (EOP), systematically studied the antidepressant effect of EOP for the first time, and discussed the potential mechanism of its antidepressant effect. In this study, we used a mouse model of corticosterone (CORT)-induced depression, and found that EOP had a significant antidepressant effect on the symptoms of CORT-induced depression in mice, and significantly down-regulated the levels of CRH, ACTH and cortisol in the brain tissues of mice. In addition, we found that EOP treatment alleviated CORT-induced hippocampal neuron injury in mice In vitro experiments. It was also found that EOP could inhibit CORT-induced apoptosis and improve the proliferation ability and cell viability of PC12 cells. Further, with the help of network analysis, it was revealed that PI3K-Akt might be one of the main signaling pathways of EOP against CORT-induced hippocampal neuron apoptosis. In this study, we also found that EOP up-regulated the phosphorylation of PI3K and Akt in CORT-induced mouse hippocampal neurons and PC12 cells, and promoted the nuclear transcription of Nrf2 in CORT-induced PC12 cells. In conclusion, with the integrated approach, we demonstrated that EOP exerted anti-apoptotic effects on hippocampal neurons through PI3K/Akt/Nrf2 signaling pathway.
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Asthma is a high-incidence disease in the world. Oxysophocarpine (OSC), a quinolizidine alkaloid displays various pharmacological functions including anti-inflammation, neuroprotective, anti-virus and antioxidant. Here, we established mice and cell asthmatic model to explore the effects of OSC for asthma treatment. Mice were sensitized and challenged with ovalbumin (OVA) and treated with OSC before challenge. Enzyme-linked immuno sorbent assay (ELISA), hematoxylin and eosin (H&E), periodic acid-schiff (PAS), tolonium chloride staining and immunohistochemical assay were performed. OSC treatment inhibited inflammatory cell infiltration and mucus secretion in the airway, reduced IgE level in mouse serum and decreased IL-4, IL-5 production in bronchoalveolar lavage fluid (BALF). OSC also reduced the spleen index to regulate immune function. Meanwhile, NCI-H292 cells were induced by lipopolysaccharide (LPS) to simulate airway epithelial injury. OSC pretreatment decreased the IL-6 and IL-8 cytokine levels, mucin 5 AC expression, and mucin 5 AC mRNA level in the cell model. Further, OSC suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), and activator protein 1 (AP-1, Fos and Jun). These findings revealed that OSC alleviated bronchial asthma associated with JNK/AP-1 signaling pathway.
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Alcaloides , Asma , Quinolizidinas , Alcaloides/metabolismo , Alcaloides/farmacologia , Animais , Antioxidantes/farmacologia , Asma/tratamento farmacológico , Citocinas/metabolismo , Modelos Animais de Doenças , Amarelo de Eosina-(YS)/metabolismo , Amarelo de Eosina-(YS)/farmacologia , Amarelo de Eosina-(YS)/uso terapêutico , Hematoxilina/metabolismo , Hematoxilina/farmacologia , Hematoxilina/uso terapêutico , Imunoglobulina E , Interleucina-4/metabolismo , Interleucina-4/farmacologia , Interleucina-4/uso terapêutico , Interleucina-5/metabolismo , Interleucina-5/farmacologia , Interleucina-5/uso terapêutico , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Lipopolissacarídeos/farmacologia , Pulmão , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Mucinas/metabolismo , Mucinas/farmacologia , Mucinas/uso terapêutico , Muco/metabolismo , Ovalbumina/metabolismo , Ácido Periódico/metabolismo , Ácido Periódico/farmacologia , Ácido Periódico/uso terapêutico , Quinolizidinas/farmacologia , RNA Mensageiro/metabolismo , Cloreto de Tolônio/metabolismo , Cloreto de Tolônio/farmacologia , Cloreto de Tolônio/uso terapêutico , Fator de Transcrição AP-1/metabolismo , Fator de Transcrição AP-1/farmacologia , Fator de Transcrição AP-1/uso terapêuticoRESUMO
Staphylococcus capitis, which causes bloodstream infections in neonatal intensive care units, is a common cause of healthcare-associated infections. Thus, a standardized high-resolution typing method to document the transmission and dissemination of multidrug-resistant S. capitis isolates is required. We aimed to establish a core genome multilocus sequence typing (cgMLST) scheme to surveil S. capitis. The cgMLST scheme was defined based on primary and validation genome sets and tested with outbreaks of linezolid-resistant isolates and a validation set. Phylogenetic analysis was performed to investigate the population structure and compare it with the result of cgMLST analysis. The S. capitis population consists of 1 dominant, NRCS-A, and 4 less common clones. In this work, a multidrug-resistant clone (L clone) with linezolid resistance is identified. With the features of type III SCCmec and multiple copies of mutations of G2576T and C2104T in the 23S rRNA, the L clone has been spreading silently across China.
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Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Staphylococcus capitis , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Humanos , Recém-Nascido , Linezolida/farmacologia , Linezolida/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/genética , Tipagem de Sequências Multilocus/métodos , Filogenia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Staphylococcus capitis/genéticaRESUMO
BACKGROUND: Rhodiola crenulate (R. crenulate), a famous Tibetan medicine, has been demonstrated to possess superiorly protective effects in high-altitude hypoxic brain injury (HHBI). However, its mechanisms on HHBI are still largely unknown. METHODS: Herein, the protective effects and underlying mechanisms of R. crenulate on HHBI of BABL/c mice were explored through in vivo experiments. The mice model of HHBI was established using an animal hypobaric and hypoxic chamber. R. crenulate extract (RCE) (0.5, 1.0 and 2.0 g/kg) was given by gavage for 7 days. Pathological changes and neuronal viability of mice hippocampus and cortex were evaluated using H&E and Nissl staining, respectively. The brain water content (BWC) in mice was determined by calculating the ratio of dry to wet weight of brain tissue. And serum of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH-Px) and lactate dehydrogenase (LDH) were detected via commercial biochemical kits. Synchronously, the contents of total antioxidant capacity (T-AOC), lactic acid (LA), adenosine triphosphate (ATP), succinate dehydrogenase (SDH), pyruvate kinase (PK), Ca2+-Mg2+-ATPcase, Na+-K+-ATPcase, TNF-α, IL-1ß and IL-6 in brain tissue were quantitative analysis by corresponding ELISA assay. Subsequently, NLRP3, ZO-1, claudin-5, occluding, p-p65, p65, ASC, cleaved-caspase-1, caspase-1 and IL-18 were determined by immunofluorescent and western blot analyses. RESULTS: The results demonstrated that RCE remarkably alleviated pathological damage, BWC, as well enhanced neuronal viability. Furthermore, the oxidative stress injuries were reversely abrogated after RCE treatment, evidenced by the increases of SOD, GSH-Px and T-AOC, while the decreases of MDA and LDH contents. Marvelously, the administration of RCE rectified and balanced the abnormal energy metabolism via elevating the levels of ATP, SDH, PK, Ca2+-Mg2+-ATPcase and Na+-K+-ATPcase, and lowering LA. Simultaneously, the expression of tight junction proteins (ZO-1, claudin-5 and occludin) was enhanced, illustrating RCE treatment might maintain the integrity of blood-brain barrier (BBB). Additionally, RCE treatment confined the contents of IL-6, IL-1ß and TNF-α, and attenuated fluorescent signal of NLRP3 protein. Concurrently, the results of western blot indicated that RCE treatment dramatically restrained p-p65/p65, ASC, NLRP3, cleaved-caspase-1/caspase-1 and IL-18 protein expressions in brain tissues of mice. CONCLUSION: RCE may afford a protectively intervention in HHBI of mice through suppressing the oxidative stress, improving energy metabolism and the integrity of BBB, and subsiding inflammatory responses via the NF-κB/NLRP3 signaling pathway. As a promising agent for the treatment of mice HHBI, the deep-crossing molecular mechanisms of R. crenulate still needs to be further elucidated to identify novel core hub targets.
Assuntos
Lesões Encefálicas , Rhodiola , Trifosfato de Adenosina , Animais , Antioxidantes/metabolismo , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Caspase 1 , Claudina-5 , Hipóxia/tratamento farmacológico , Inflamação/metabolismo , Interleucina-18/uso terapêutico , Interleucina-6 , Camundongos , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfaRESUMO
LINC01133 is a long intergenic non-coding RNA that regulates malignancy in several cancers, including those of the digestive, female reproductive, respiratory, and urinary system. LINC01133 is an extensively studied lncRNA that is highly conserved, and its relatively stable expression is essential for its robust biological function. Its expression is highly tissue-specific with a distinct subcellular localization. It functions as an oncogene or a tumor suppressor gene in different cancers via multiple mechanisms, such as those that involve competing with endogenous RNA and binding to RNA-binding proteins or DNA. Moreover, the secretion and transportation of LINC01133 by extracellular vesicles in the tumor micro-environment is regulated by other cells in the tumor micro-environment. To date, two mechanisms, an increase in copy number and regulation of transcription elements, have been found to regulate LINC01133 expression. Clinically, LINC01133 is an ideal marker for cancer prognosis and a potential therapeutic target in cancer treatment regimes. In this review, we aimed to summarize the aforementioned information as well as posit future directions for LINC01133 research.
RESUMO
BACKGROUND: Bacteria-mediated cancer immunotherapy (BCI) robustly stimulates the immune system and represses angiogenesis, but tumor recurrence and metastasis commonly occur after BCI. The natural product Ilex kudingcha C. J Tseng enriched with ursolic acid has anti-cancer activity and could potentially augment the therapeutic effects of BCI. The objective of the present study was to determine potential additive effects of these modalities. METHODS: We investigated the anti-cancer activity of KDCE (Kudingcha extract) combined with S.tâ³ppGpp in the mice colon cancer models. RESULTS: In the present study, KDCE combined with S.tâ³ppGpp BCI improved antitumor therapeutic efficacy compared to S.tâ³ppGpp or KDCE alone. KDCE did not prolong bacterial tumor-colonizing time, but enhanced the antiangiogenic effect of S.tâ³ppGpp by downregulatingVEGFR2. We speculated that KDCE-induced VEGFR2 downregulation is associated with FAK/MMP9/STAT3 axis but not AKT or ERK. CONCLUSIONS: Ursolic acid-enriched KDCE enhances the antitumor activity of BCI, which could be mediated by VEGFR2 downregulation and subsequent suppression of angiogenesis. Therefore, combination therapy with S.tâ³ppGpp and KDCE is a potential cancer therapeutic strategy.
Assuntos
Ilex , Neoplasias , Animais , Bactérias , Modelos Animais de Doenças , Imunoterapia , Camundongos , Extratos Vegetais/farmacologia , Triterpenos , Ácido UrsólicoRESUMO
Salidroside (Sal), an active ingredient from Rhodiola crenulate, has been reported to exert neuroprotection in cerebral injury from hypobaric hypoxia (HH) at high altitude. However, it remains to be understood whether its protective effects are related to inflammation suppression. In the present work, we aimed to reveal the mechanism of Sal attenuating HH-induced brain injury in mice caused by an animal hypobaric and hypoxic chamber. Our results provided that Sal could attenuate HH-evoked pathological injury and oxidative stress response by decreasing the content of ROS and MDA, and elevating the activities of SOD and GSH-Px. Sal treatment could partly enhance the energy metabolism, evidenced by increasing the activities of Na+-K+-ATPase, Ca2+-Mg2+-ATPase, ATP, SDH, HK and PK, while decreasing the release of LDH and LD. Meanwhile, Sal administration reversed the degradation of tight junction proteins ZO-1, Occludin and Claudin-5. Further, the increased levels of TNF-α, IL-1ß and IL-6 were confined with Sal administration under the HH condition. Importantly, Sal could downregulate the proteins expression of p-NF-κB-p65, NLRP3, cleaved-Caspase-1 and ASC. Sal also decreased the protein expression of iNOS and COX2 with the increased CD206 and Arg1 expression. Taken together, these data provided that the inhibited NF-κB/NLRP3 pathway by Sal could attenuate HH-induced cerebral oxidative stress injury, inflammatory responses and the blood brain barrier (BBB) damage, attributing to the improved energy metabolism and the microglial phenotype of anti-inflammatory M2. The findings suggested that Sal was expected to be a promising anti-inflammatory agent for high altitude HH-induced brain injury.