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Salmonella enterica serovar Typhimurium (S. Tm) causes severe foodborne diseases. Interestingly, gut microbial tryptophan (Trp) metabolism plays a pivotal role in such infections by a yet unknown mechanism. This study aimed to explore the impact of Trp metabolism on S. Tm infection and the possible mechanisms involved. S. Tm-infected C57BL6/J mice were used to demonstrate the therapeutic benefits of the Bacillus velezensis JT3-1 (B. velezensis/JT3-1) strain or its cell-free supernatant in enhancing Trp metabolism. Targeted Trp metabolomic analyses indicated the predominance of indole-3-lactic acid (ILA), an indole derivative and ligand for aryl hydrocarbon receptor (AHR). Based on the 16S amplicon sequencing and correlation analysis of metabolites, we found that B. velezensis supported the relative abundance of Lactobacillus and Ligilactobacillus in mouse gut and showed positive correlations with ILA levels. Moreover, AHR and its downstream genes (especially IL-22) significantly increased in mouse colons after B. velezensis or cell-free supernatant treatment, suggesting the importance of AHR pathway activation. In addition, ILA was found to stimulate primary mouse macrophages to secrete IL-22, which was antagonized by CH-223191. Furthermore, ILA could protect mice from S. Tm infection by increasing IL-22 in Ahr+/- mice, but not in Ahr-/- mice. Finally, Trp-rich feeding showed amelioration of S. Tm infection in mice, and the effect depended on gut microbiota. Taken together, these results suggest that B. velezensis-associated ILA contributes to protecting mice against S. Tm infection by activating the AHR/IL-22 pathway. This study provides insights into the involvement of microbiota-derived Trp catabolites in protecting against Salmonella infection.
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Microbioma Gastrointestinal , Microbiota , Infecções por Salmonella , Animais , Camundongos , Salmonella typhimurium , Triptofano/metabolismo , Receptores de Hidrocarboneto Arílico/genética , Receptores de Hidrocarboneto Arílico/metabolismoRESUMO
Photosynthesis is a complex multi-step process in which light collection is the initial step of photosynthesis and plays an important role in the efficiency of solar energy utilization. In order to improve the utilization of sunlight, researchers have developed a variety of artificial light-harvesting system to simulate photosynthesis in nature. Here, we report a supramolecular self-assembly artificial light-harvesting system in aqueous solution. We modified ß-CD with the donor molecule naphthalimide and adamantane with the tetraphenylethylene molecule which has aggregation-induced emission effects (AIE). By using fluorescent molecules with AIE, the self-quenching effect caused by aggregation in aqueous solution can be effectively avoided. Due to the host-guest interaction of ß-CD and adamantane, nanoparticles with stable structure and uniform size can be spontaneously assembled in water. Because of the close distance and strong spectral overlap between naphthalimide and tetraphenylethylene, Förster resonance energy transfer (FRET) was realized, and artificial light-harvesting system was successfully constructed in aqueous solution. The light-harvesting system has a high energy transfer efficiency (ΦET). Therefore, this study provides a new strategy for constructing artificial light-harvesting system.
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OBJECTIVE: This study aimed to investigate the association between a history of recurrent spontaneous abortion (RSA) and adverse outcomes in women with spontaneous conception. METHODS: A search strategy from the inception to March 3, 2023 was run in PubMed, Embase, Cochrane Library, and Web of Science databases. The odds ratio (OR), and the 95% confidence interval (CI) or point estimation were used as the evaluation indexes. Each outcome measure tested was assessed for heterogeneity using the Cochran Q test. Sensitivity analyses were performed to test the credibility of the meta-analysis results. RESULTS: Fifteen studies involving 1 475 389 pregnant women were included. A history of RSA was associated with gestational diabetes (OR: 2.21, 95% CI: 1.70-2.87, p < 0.001), preeclampsia (OR: 2.06, 95% CI: 1.49-2.86, p < 0.001), placenta previa (OR: 1.82, 95% CI: 1.09-3.02, p = 0.021), placental abruption (OR: 1.67, 95% CI: 1.36-2.06, p < 0.001), miscarriage (OR: 6.37, 95% CI: 3.83-10.57, p < 0.001), preterm birth (OR: 1.80, 95% CI: 1.36-2.37, p < 0.001), cesarean section (OR: 1.47, 95% CI: (1.13-1.91, p = 0.004), perinatal death (OR: 2.24, 95% CI: 1.39-3.60, p = 0.001), and neonatal intensive care unit admission (OR: 1.39, 95% CI: 1.01-1.92, p = 0.047). However, the associations of a history of RSA with gestational hypertension, small for gestational age, fetal anomalies, fetal growth restriction, and postpartum hemorrhage were not observed. CONCLUSION: This meta-analysis indicates a history of RSA was associated with increased risks of several adverse outcomes in pregnant women with spontaneous conception.
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Aborto Habitual , Descolamento Prematuro da Placenta , Nascimento Prematuro , Recém-Nascido , Gravidez , Feminino , Humanos , Cesárea , Placenta , Aborto Habitual/epidemiologia , Aborto Habitual/etiologia , Retardo do Crescimento FetalRESUMO
OBJECTIVE: Chronic kidney disease (CKD) is a condition influenced by both genetic and environmental factors and has been a focus of extensive research. Utilizing Mendelian randomization, researchers have begun to untangle the complex causal relationships underlying CKD. This review delves into the advances and challenges in the application of MR in the field of nephrology, shifting from a mere summary of its principles and limitations to a more nuanced exploration of its contributions to our understanding of CKD. METHODS: Key findings from recent studies have been pivotal in reshaping our comprehension of CKD. Notably, evidence indicates that elevated testosterone levels may impair renal function, while higher sex hormone-binding globulin (SHBG) levels appear to be protective, predominantly in men. Surprisingly, variations in plasma glucose and glycated hemoglobin levels seem unaffected by genetically induced changes in the estimated glomerular filtration rate (eGFR), suggesting an independent pathway for renal function impairment. RESULTS: Furthermore, lifestyle factors such as physical activity and socioeconomic status emerge as significant influencers of CKD risk and kidney health. The relationship between sleep duration and CKD is nuanced; short sleep duration is linked to increased risk, while long sleep duration does not exhibit a clear causal effect. Additionally, lifestyle factors, including diet, exercise, and mental wellness activities, play a crucial role in kidney health. New insights also reveal a substantial causal connection between both central and general obesity and CKD onset, while no significant links were found between genetically modified LDL cholesterol or triglyceride levels and kidney function. CONCLUSION: This review not only presents the recent achievements of MR in CKD research but also illuminates the path forwards, underscoring critical unanswered questions and proposing future research directions in this dynamic field.
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Insuficiência Renal Crônica , Insuficiência Renal , Masculino , Humanos , Análise da Randomização Mendeliana , Insuficiência Renal Crônica/genética , Rim , LDL-Colesterol , Estudo de Associação Genômica AmplaRESUMO
Despite Bacillus species having been extensively utilized in the food industry and biocontrol as part of probiotic preparations, limited knowledge exists regarding their impact on intestinal disorders. In this study, we investigated the effect of Bacillus licheniformis ZW3 (ZW3), a potential probiotic isolated from camel feces, on dextran sulfate sodium (DSS)-induced colitis. The results showed ZW3 partially mitigated body weight loss, disease activity index (DAI), colon shortening, and suppressed immune response in colitis mice, as evidenced by the reduction in the levels of the inflammatory markers IL-1ß, TNF-α, and IL-6 (p < 0.05). ZW3 was found to ameliorate DSS-induced dysfunction of the colonic barrier by enhancing mucin 2 (MUC2), zonula occluden-1 (ZO-1), and occludin. Furthermore, enriched beneficial bacteria Lachnospiraceae_NK4A136_group and decreased harmful bacteria Escherichia-Shigella revealed that ZW3 improved the imbalanced gut microbiota. Abnormally elevated uric acid levels in colitis were further normalized upon ZW3 supplementation. Overall, this study emphasized the protective effects of ZW3 in colitis mice as well as some potential applications in the management of inflammation-related diseases.
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Bacillus licheniformis , Bacillus , Colite , Probióticos , Animais , Camundongos , Colite/induzido quimicamente , Colite/terapia , Camelus , Homeostase , Probióticos/farmacologia , Probióticos/uso terapêuticoRESUMO
BACKGROUND: Probiotics can reduce free radical scavenging rate and oxidative damage, and improve activity of crucial antioxidative enzymes in host cells. This study aimed to isolate Bifidobacterium spp. from faeces of babies, and investigate the antioxidant effects of the Bif. longum T37a in mice weight loss and aging model induced by D-galactose. RESULTS: T37a have good antioxidant properties in the DPPH assay and anti-lipid peroxidation test. Compared with the model group, T37a low group significantly increased the thymus index and the levels of T-AOC and GSH-Px of mice. T37a high group significantly decreased the spleen and liver index of mice and the levels of MDA in liver, significantly increased in liver HDL-C levels, and decreased LDL-C in liver. CONCLUSIONS: T37a may be an anti-aging and weight-loss probiotics for its antioxidant capacity, and it is necessary to study further the molecular mechanism of T37a as antioxidant.
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Antioxidantes , Bifidobacterium longum , Humanos , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Galactose/farmacologia , Bifidobacterium/metabolismo , Estresse Oxidativo , Redução de PesoRESUMO
PURPOSE OF REVIEW: We aim to review the neurological complications of HIV and the social, cultural, and economic inequalities that contribute to disparities in neuroHIV care. RECENT FINDINGS: Disparities in diagnostics and care of patients with neurological infections and non-infectious conditions associated with HIV in both high-income and low-to-middle-income countries (LMIC) are common. The COVID-19 pandemic has exacerbated these disparities. Factors, such as HIV-related stigma, may deter people from accessing HIV treatment. First-line recommended treatments for neurological infections are not available in many LMICs, leading to inadequate treatment and exposure to agents with more harmful side effect profiles. Access-related factors, such as lack of transportation, lack of health insurance, and inadequate telehealth access, may increase the risk of HIV-related neurological complications. Further research is needed to increase awareness of neurological complications among providers and PWH, and regional guidelines should be considered to better address these complications.
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Infecções por HIV , Disparidades em Assistência à Saúde , Humanos , Pandemias , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Continuidade da Assistência ao Paciente , Países em DesenvolvimentoRESUMO
The seeds of Vitex negundo have been used for inflammation-related disease treatment in traditional medicine. This study focused on the anti-osteoarthritis (OA) effects of the total lignans of V. negundo seeds (TOV) in monosodium iodoacetate-induced osteoarthritis rats and its pharmacokinetic properties, as well as the effects and potential mechanism of its main components VN1 (6-hydroxy-4-(4-hydroxy-3-methoxy-phenyl)-3-hydro-xymethyl-7-methoxy-3,4-dihydro-2-naphthaldehydeb) and VN2 (vitedoin A) on receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation in bone marrow macrophages (BMMs). TOV significantly attenuated osteoarthritis, leading to an increase in pain thresholds, improvement of knee articular cartilages and chondrocytes loss, and decreased total joint scores and serum levels of TNF-α, interleukin-1ß (IL-1ß), and prostaglandin E2 (PGE2) in osteoarthritis rats. The half-time (T1/2 ) was 2.82 h and 1.33 h, and the bioavailability was 15.34%-21.89% and 16.29%-22.11%, for VN1 and VN2, respectively. VN2, rather than VN1, remarkably inhibited tartrate-resistant acid phosphatase (TRAP) activity, reduced the number of TRAP-positive multinuclear cells, diminished the formation of actin ring, and decreased mRNA levels of cathepsin K (CTSK), TRAP, nuclear factor of activated T cell 1 (NFATc1), and osteoclast-associated receptor, as well as downregulated protein levels of p-ERK (phosphorylated extracellular signal-regulated kinase), TRAP, CTSK and NFATc1 in BMMs. These findings suggest TOV has promising therapeutic potential for OA treatment and VN2, in particular, attenuates osteoclast differentiation by suppressing ERK/NFATc1 signaling and actin ring, mainly accounting for the anti-OA efficacy of TOV.
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Lignanas , Vitex , Ratos , Animais , Osteoclastos , Vitex/metabolismo , Actinas/metabolismo , Linfócitos T , Lignanas/farmacologia , Diferenciação CelularRESUMO
Thyroid hormones are involved in numerous physiological processes as regulators of metabolism, regulating organ growth, and mental state. Bisphenol compounds (BPs) are recognized as chemicals that interfere with endocrine balance. Because BPs have a similar structure to thyroxine, they can compete for binding to thyroid protein and disrupt the normal physiological activity of the thyroid system. In this study, three typical bisphenol compounds were selected to explore the interaction between BPs and TTR by computer simulations and multi-spectroscopic methods. The results revealed that BPs quenched the endogenous fluorescence of TTR via the combination of static quenching and non-radiative energy transfer, and the van der Waals forces and hydrogen bonding played a synergistic role in the binding process of BPs and TTR. Furthermore, the three-dimensional fluorescence spectroscopy, UV-vis spectroscopy, and Fourier transform infrared (FT-IR) spectroscopy, which were employed to determine the conformation of protein, revealed that binding of BPs with TTR could induce conformational changes in TTR. In addition, the binding sites and the residues surrounding the BPs within the TTR were determined through molecular docking and molecular dynamics simulation. Therefore, this work provides new insights into the interaction between BPs and TTR to evaluate the potential toxicity of BPs.
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Simulação de Dinâmica Molecular , Pré-Albumina , Sítios de Ligação , Ligação de Hidrogênio , Simulação de Acoplamento Molecular , Pré-Albumina/metabolismo , Ligação Proteica , Espectrometria de Fluorescência , Espectroscopia de Infravermelho com Transformada de Fourier , TermodinâmicaRESUMO
The role of adjunctive corticosteroids in reducing morbidity and mortality of viral CNS infections remains poorly defined. Clinicians are often left in a quagmire regarding steroid use in complex and rapidly evolving viral CNS infections. Limited studies have explored the underlying mechanisms behind the potential benefit of steroids. Here, we describe steroid use in three cases of viral CNS disease: varicella zoster virus (VZV), Powassan virus, and influenza A-associated acute necrotizing encephalopathy.
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Viroses do Sistema Nervoso Central , Herpes Zoster , Corticosteroides/uso terapêutico , Sistema Nervoso Central , Viroses do Sistema Nervoso Central/tratamento farmacológico , Herpesvirus Humano 3/fisiologia , Humanos , Esteroides/uso terapêuticoRESUMO
In this study, we screened bacterial strains to identify specific probiotics to treat pig diarrhea caused by Escherichia coli or Salmonella. The potential probiotics were assayed for their survival in gastrointestinal solution, their antimicrobial activity, cell-surface properties, adhesion to Caco-2 cells, and inhibition of pathogen adhesion. Nine out of the 20 strains tested showed high tolerance of a simulated gastrointestinal environment and six strains exerted antagonistic effects against enterohemorrhagic E. coli (EHEC) O157:H7 and Salmonella Typhimurium MQ. Lactobacillus johnsonii pDX1e exhibited a higher potent antibacterial activity. Four strains (pDX1a, pDX1e, pDX3a, and pDX5a) displayed auto-aggregation, hydrophobicity, and adhesion to Caco-2 cells similar to those of the reference strain Lacticaseibacillus rhamnosus GG (LGG). Enterococcus durans pDX5a showed the highest adhesion capacity (13.86%), followed by the reference strain LGG (11.20%). All the tested strains competitively suppressed the attachment of pathogens to Caco-2 cells (by 30.73-55.18%); L. johnsonii pDX1e and Ent. durans pDX5a significantly inhibited the adhesion of pathogens by substitution and exclusion, respectively. Therefore, pDX1e and pDX5a were selected as probiotic strains for further investigation and application.
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Escherichia coli O157 , Probióticos , Animais , Aderência Bacteriana , Células CACO-2 , Enterococcus , Humanos , Lactobacillus , Salmonella typhimurium , SuínosRESUMO
Shock waves and micro-jets generated during the process of bubble collapse lead to cavitation damage on the surface of materials in hydraulic machinery equipment parts, which is attention. However, research on the dynamics of bubble collapse is still unclear. In this work, molecular dynamics (MD) simulations are used to study the compression and collapse processes of microscopic bubbles under the impact of different velocities for water molecules. The velocities of the shock wave, time of bubble collapse and shock pressure of collapse were obtained. Results showed that higher the impact velocity, shorter is the time of bubble collapse and the higher velocity of the micro-jet. After the bubble collapse, the micro-jet will form secondary water hammer shocks and a greater shock pressure. The water structure appears to undergo a phase change (ice-VII structure) when the velocity of water molecules is 1.0 km s-1. The shock induces the bubble collapse and the micro-jet significantly increases the chemical activity of water molecules; the degree of ionization of water molecules increases with the shock velocity. In addition, the Hugoniot curve of the shock velocity obtained by molecular dynamics simulations are in good agreement with the experimental data.
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Rictor is a key component of the mammalian target of rapamycin complex 2 (mTORC2) and is required for Akt phosphorylation (Ser473). Our previous study shows that knockdown of Rictor prevents cardiomyocyte differentiation from mouse embryonic stem (ES) cells and induces abnormal electrophysiology of ES cell-derived cardiomyocytes (ESC-CMs). Besides, knockdown of Rictor causes down-expression of connexin 43 (Cx43), the predominant gap junction protein, that is located in both the sarcolemma and mitochondria in cardiomyocytes. Mitochondrial Cx43 (mtCx43) plays a crucial role in mitochondrial function. In this study, we used the model of cardiomyocyte differentiation from mouse ES cells to elucidate the mechanisms for the mitochondrial damage in ESC-CMs after knockdown of Rictor. We showed swollen and ruptured mitochondria were observed after knockdown of Rictor under transmission electron microscope. ATP production and mitochondrial transmembrane potential were significantly decreased in Rictor-knockdown cells. Furthermore, knockdown of Rictor inhibited the activities of mitochondrial respiratory chain complex. The above-mentioned changes were linked to inhibiting the translocation of Cx43 into mitochondria by knockdown of Rictor. We revealed that knockdown of Rictor inactivated the mTOR/Akt signalling pathway and subsequently decreased HDAC6 expression, resulted in Hsp90 hyper-acetylation caused by HDAC6 inhibition, thus, inhibited the formation of Hsp90-Cx43-TOM20 complex. In conclusion, the mitochondrial Cx43 participates in shRNA-Rictor-induced mitochondrial function damage in the ESC-CMs.
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Conexina 43/metabolismo , Alvo Mecanístico do Complexo 2 de Rapamicina/metabolismo , Mitocôndrias Cardíacas/metabolismo , Células-Tronco Embrionárias Murinas/metabolismo , Miócitos Cardíacos/metabolismo , Proteína Companheira de mTOR Insensível à Rapamicina/metabolismo , Animais , Diferenciação Celular/fisiologia , Conexina 43/genética , Alvo Mecanístico do Complexo 2 de Rapamicina/antagonistas & inibidores , Alvo Mecanístico do Complexo 2 de Rapamicina/genética , Potencial da Membrana Mitocondrial/fisiologia , Camundongos , Proteína Companheira de mTOR Insensível à Rapamicina/antagonistas & inibidores , Proteína Companheira de mTOR Insensível à Rapamicina/genéticaRESUMO
BACKGROUND: Eosinophilic pleural effusion (EPE) is a distinct entity among pleural effusions, but its diagnostic and prognostic significance is still controversial. This study aimed to evaluate the incidence and aetiological distribution of EPE in our institution and to assess the relationship between EPE and malignancy and other underlying diseases and the relevance of the percentage of eosinophils and other laboratory parameters. METHODS: A retrospective study was conducted by reviewing the medical records of 252 patients with PE from September 2017 to January 2021. RESULTS: EPE was found in 34 (13.49%) out of 252 patients. There were 20 (58.82%) males and 14 (41.18%) females in the EPE group. The mean percentage of eosinophils in EPE (21.7%, range (10.0-67.5%)) was significantly higher than the percentage of eosinophils in peripheral blood (5.65%, range (0-34.60%); p < 0.05). The most common cause of EPE was malignant disease (52.94%), followed by idiopathy (14.71%), parasites (8.82%), pneumonia (8.82%) and others (14.71%). Comparative analysis of patients with malignant versus nonmalignant EPE showed that patients with malignant EPE were significantly older, and had a lower white blood cell (WBC) count in the pleural fluid (1.8 vs 4.7 cells × 109/L, p < 0.05). However, the percentage of eosinophils in PE was not significantly different between malignant EPE and nonmalignant EPE (p = 0.66). There was no correlation between the percentage of eosinophils in PE and peripheral blood (r = 0.29; p = 0.09). CONCLUSIONS: Malignant disease ranks as the leading cause of EPE. The presence of EPE should not be considered as a predictive factor of benign conditions. Pleural parasitic infestation (PPI) should be emphasized in areas with a high incidence of parasitic disease.
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Eosinofilia/sangue , Eosinofilia/epidemiologia , Derrame Pleural/sangue , Derrame Pleural/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Comorbidade , Eosinofilia/patologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Derrame Pleural/patologia , Estudos RetrospectivosRESUMO
The objectives of this study were to evaluate the effects of different salinity levels on tissue histology, blood biochemistry, and genes transcription of the GH/IGF system in juvenile golden trout (Oncorhynchus mykiss). Five experimental salinity levels (0, 8, 16, 24, and 32) were selected to domesticate juvenile O. mykiss for 7 days. Histological characteristics changed with salinity, including higher ionocites area and epithelium thickness in gills, narrow lumen of collecting tubules in kidneys, and high numbers of goblet cells in the intestines. Similarly, increments in slits, degenerate hepatocytes, and individualization of hepatocytes have been shown in fish reared in the 32 salinity group. The lowest triglyceride (TG) and the highest level of total protein (TP) were detected in fish reared at the 32 group. The genes transcription of the GH/IGF system altered in response to the increase of salinity. The present results add to the understanding of the physiological responses of O. mykiss on salinity stress and would be helpful in formulating strategies to optimize the aquaculture of this species in environments with fluctuating patterns of salinity.
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Hormônio do Crescimento/metabolismo , Oncorhynchus mykiss/crescimento & desenvolvimento , Salinidade , Somatomedinas/metabolismo , Água/química , Adaptação Fisiológica/efeitos dos fármacos , Animais , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônio do Crescimento/genética , Cloreto de Sódio/química , Cloreto de Sódio/farmacologia , Somatomedinas/genéticaRESUMO
Skin-whitening effect is closely linked with the melanogenesis inhibitory activity and free radical scavenging capacity. The purpose of the present study was to evaluate the skin-whitening effect of cumin (Cuminum cyminum L.) extract. The whitening activity was evaluated by cell-free mushroom tyrosinase assay, free radical scavenging assay, cell viability assay, cellular tyrosinase assay and melanin content assay using B16F10 murine melanoma cells. The results showed that cumin extract exhibited concentration-dependent inhibitory effect on both monophenolase and diphenolase activities of mushroom tyrosinase (IC50 values of 1.027mg/mL and 0.977mg/mL, respectively). Kinetic study on diphenolase showed that the cumin extract was a reversible mixed-type inhibitor, and the inhibition constant (KI) was determined to be 0.62mg/mL. In addition, cumin extract significantly suppressed melanin production and cellular tyrosinase activity of B16F10 melanoma cells in a concentration and time dependent manner without cytotoxicity. Moreover, cumin extract exerted strong scavenging capacity on DPPH, hydroxyl and superoxide anion radicals. Taken together, these results strongly suggest that cumin is a potential skin-whitening agent for the cosmetic industry.
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Sobrevivência Celular/efeitos dos fármacos , Cuminum , Sequestradores de Radicais Livres/farmacologia , Extratos Vegetais/farmacologia , Preparações Clareadoras de Pele/farmacologia , Pele/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Sobrevivência Celular/fisiologia , Relação Dose-Resposta a Droga , Sequestradores de Radicais Livres/isolamento & purificação , Melanoma Experimental , Camundongos , Extratos Vegetais/isolamento & purificação , Pele/metabolismo , Preparações Clareadoras de Pele/isolamento & purificaçãoRESUMO
Enteroviruses (EV) are responsible for a large number of meningoencephalitis cases, especially in children. The objective of this study was to identify modes of diagnosis including the significance of respiratory and cerebrospinal fluid samples, associated clinical characteristics, inpatient management, and outcome of individuals with EV infections of the central nervous system (CNS). Electronic medical records of individuals with enterovirus infections of the CNS who presented to the Columbia University Irving Medical Center and Children's Hospital of New York between January 1, 2012 and December 31, 2017 were reviewed retrospectively for demographic, epidemiological, and clinical data. The median age overall was 1.7 months (interquartile range 14 years) and most (62.4%) were male. The majority of CNS infections presented as meningitis (95.7%) and occurred in the summer (45.2%) and fall seasons (37.6%). Eighty-five cases (91.4%) demonstrated EV positivity in cerebrospinal fluid, thirty cases (32.3%) exhibited both cerebrospinal fluid and respiratory positivity, and eight cases (8.6%) exhibited respiratory positivity with coinciding neurological findings. Eighty-nine individuals overall (95.7%) received antibiotics and 37 (39.8%) received antiviral treatment. All surviving individuals had favorable Modified Rankin Scores (MRS) within the zero to two ranges upon discharge. Testing respiratory samples in addition to cerebrospinal fluid was found to be an important diagnostic tool in EV-associated cases. While clinical outcomes were favorable for an overwhelming majority of cases, etiological understanding of CNS infections is essential for identifying ongoing and changing epidemiological patterns and aid in improving the diagnosis and treatment.
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Infecções por Enterovirus , Meningoencefalite/virologia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos RetrospectivosRESUMO
INTRODUCTION: Acute respiratory distress syndrome (ARDS) is a life-threatening medical condition. It is characterized by serious lung inflammation or injury. Characterizing novel miRNAs implicated in ARDS pathogenesis may provide new therapeutic strategy for managing ARDS. METHODS: We employed LPS-induced lung injury model to profile miRNAs associated with ARDS. We isolated one miRNA candidate and characterized its role in lipopolysaccharide (LPS)-induced proinflammatory cytokine production in lung macrophages. We further evaluated its functional role in ARDS model by assessing histological change, neutrophil activation, tissue permeability and tumor necrosis factor alpha (TNFα) production. We also characterized its downstream target using luciferase assay, Western blotting, enzyme-linked immunosorbent assay and cell inflammation assay. RESULTS: Microarray profiling revealed miR-802 was significantly downregulated in ARDS mouse model. LPS-induced miR-802 downregulation was confirmed in lung macrophages. Overexpression of miR-802 significantly suppressed LPS-induced inflammatory cytokine production in vitro and alleviates LPS-induced acute lung injury in vivo. Peli2 was identified as a downstream target of miR-802 and found upregulated in ARDS model. Overexpressing Peli2 abolished the antagonizing effect of miR-802 on LPS-mediated inflammatory response. CONCLUSION: MiR-802 carried a protective role against LPS-induced acute lung injury by downregulating Peli2. MiR-802/Peli2 axis may act as intervening targets to manage ARDS.
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Lesão Pulmonar Aguda/genética , MicroRNAs/genética , Proteínas Nucleares/genética , Síndrome do Desconforto Respiratório/genética , Ubiquitina-Proteína Ligases/genética , Células A549 , Lesão Pulmonar Aguda/induzido quimicamente , Animais , Citocinas/genética , Modelos Animais de Doenças , Regulação para Baixo , Humanos , Lipopolissacarídeos , Macrófagos Alveolares/metabolismo , Camundongos , Células RAW 264.7RESUMO
Structural modification of active natural compoundswhichwereoriginated fromTraditional Chinese Medicine (TCM) have showedgreat advantagesin thedevelopmentof new drugs. In TCM, "Huangqin-Huanglian" is a classic "medicine couple"thathas been used to treat intestinal diseases for thousands ofyears, while baicalinand berberine are the major active compoundsof Huangqin and Huanglianrespectively. Based onthis"medicine couple",wedesignedand synthesizeda newbaicalin and berberine hybrid compound (BBH).Its molecular structure wasconfirmedby spectroscopy.The antibacterial activity of BBH was detected in vitro.Results indicatedthat the new hybrid compound exhibited the best antibacterial activity forproteobacteria as compared with its original synthetic materials (baicalin andberberine). In vivo, the effect of BBHon ulcerative colitiswas alsoinvestigated.BBH treatment significantly ameliorated the disease symptoms andpreventedthe colon damage of ulcerative colitis. Furthermore, BBH showed asignificant anti-inflammatory effect through regulating activities of SOD, MPOandexpressions of pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6) in colontissue. Data also suggested that BBH was more superior than baicalin and berberine inameliorating colonic damage. This indicated that the new hybrid compound BBHshowed enhanced efficacy in treating ulcerative colitis.
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Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Bactérias/efeitos dos fármacos , Berberina/farmacologia , Colite Ulcerativa/tratamento farmacológico , Flavonoides/farmacologia , Animais , Antibacterianos/síntese química , Antibacterianos/química , Anti-Inflamatórios/síntese química , Anti-Inflamatórios/química , Berberina/química , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/patologia , Sulfato de Dextrana , Relação Dose-Resposta a Droga , Desenho de Fármacos , Flavonoides/química , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Estrutura Molecular , Relação Estrutura-Atividade , Superóxido Dismutase/antagonistas & inibidores , Superóxido Dismutase/metabolismoRESUMO
Three-dimensional (3D) printing is widely used in medicine. Most research remains focused on forming rigid anatomical models, but moving from static models to dynamic functionality could greatly aid preoperative surgical planning. This work reviews literature on dynamic 3D heart models made of flexible materials for use with a mock circulatory system. Such models allow simulation of surgical procedures under mock physiological conditions, and are; therefore, potentially very useful to clinical practice. For example, anatomical models of mitral regurgitation could provide a better display of lesion area, while dynamic 3D models could further simulate in vitro hemodynamics. Dynamic 3D models could also be used in setting standards for certain parameters for function evaluation, such as flow reserve fraction in coronary heart disease. As a bridge between medical image and clinical aid, 3D printing is now gradually changing the traditional pattern of diagnosis and treatment.