RESUMO
Tripterygium wilfordii (TW) preparations have been utilized in China for treating rheumatoid arthritis and autoimmune diseases. However, their clinical use is limited due to reproductive toxicity, notably premature ovarian failure (POF). Our study aimed to investigate the effect and mechanism of bergenin in attenuating POF induced by triptolide in mice. POF was induced in female ICR mice via oral triptolide administration (50⯵g/kg) for 60 days. Mice received bergenin (25, 50, 100â¯mg/kg, i.g.) or estradiol valerate (EV) (0.1â¯mg/kg, i.g.) daily, 1â¯h before triptolide treatment. In vitro, ovarian granulosa cells (OGCs) were exposed to triptolide (100â¯nM) and bergenin (1, 3, 10⯵M). Antioxidant enzyme activity, protein expression, apoptosis rate, and reactive oxygen species (ROS) levels were assessed. The results showed that triptolide-treated mice exhibited evident atrophy, along with an increase in atretic follicles. Bergenin (50, 100â¯mg/kg) and EV (0.1â¯mg/kg), orally administered, exerted significant anti-POF effect. Bergenin and EV also decreased apoptosis in mouse ovaries. In vitro, bergenin (1, 3, 10⯵M) attenuated triptolide-induced OGCs apoptosis by reducing levels of apoptosis-related proteins. Additionally, bergenin reduced oxidative stress through downregulation of antioxidant enzymes activity and overall ROS levels. Moreover, the combined use with Sh-Nrf2 resulted in a reduced protection of bergenin against triptolide-induced apoptosis of OGCs. Together, bergenin counteracts triptolide-caused POF in mice by inhibiting Nrf2-mediated oxidative stress and preventing OGC apoptosis. Combining bergenin with TW preparations may effectively reduce the risk of POF.
Assuntos
Antioxidantes , Apoptose , Benzopiranos , Diterpenos , Compostos de Epóxi , Células da Granulosa , Camundongos Endogâmicos ICR , Fenantrenos , Insuficiência Ovariana Primária , Espécies Reativas de Oxigênio , Animais , Feminino , Insuficiência Ovariana Primária/induzido quimicamente , Insuficiência Ovariana Primária/tratamento farmacológico , Insuficiência Ovariana Primária/prevenção & controle , Diterpenos/farmacologia , Fenantrenos/toxicidade , Fenantrenos/farmacologia , Compostos de Epóxi/toxicidade , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Benzopiranos/farmacologia , Benzopiranos/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Camundongos , Células CultivadasRESUMO
This article demonstrates an inductively coupled high-accuracy localization system for miniature ingestible devices. It utilizes an inductance double capacitances-series capacitance (LCC-S) compensation architecture that enables mutual inductance measurement at primary side that is positioned outside the human body and less constrained by power budget and size than the miniature ingestible. Depending on the secondary circuit architecture, only limited and simple cooperative measurements are needed from the ingestible secondary side, which saves power and area in the miniature device. The errors in the system are modeled thoroughly, providing insights about system require-ments for a particular localization accuracy target for efficient design and to identify key building blocks with large influence on overall performance. The model shows that sub-centimeter localization root-mean-square error (RMSE) can be achieved with a modest external ADC (18bit) using three primary coils and three secondary coils. The localization is verified along a complete small intestine tract with realistic dimensions. The proposed model is verified by simulation and experiment showing that at the selected frequency range up to 5 MHz the body has no influence on the accuracy. The use of 0.9% saline as phantom is proposed which guarantees the analysis validity for all body types.
Assuntos
Desenho de Equipamento , Humanos , Capacitância Elétrica , Tecnologia sem Fio/instrumentaçãoRESUMO
Many lines of evidence demonstrate the associations of colorectal cancer (CRC) with intestinal microbial dysbiosis. Recent reports have suggested that maintaining the homeostasis of microbiota and host might be beneficial to CRC patients, but the underlying mechanisms remain unclear. In this study, we established a CRC mouse model of microbial dysbiosis and evaluated the effects of fecal microbiota transplantation (FMT) on CRC progression. Azomethane and dextran sodium sulfate were used to induce CRC and microbial dysbiosis in mice. Intestinal microbes from healthy mice were transferred to CRC mice by enema. The vastly disordered gut microbiota of CRC mice was largely reversed by FMT. Intestinal microbiota from normal mice effectively suppressed cancer progression as assessed by measuring the diameter and number of cancerous foci and significantly prolonged survival of the CRC mice. In the intestine of mice that had received FMT, there were massive infiltration of immune cells, including CD8+ T and CD49b+ NK, which is able to directly kill cancer cells. Moreover, the accumulation of immunosuppressive cells, Foxp3+ Treg cells, seen in the CRC mice was much reduced after FMT. Additionally, FMT regulated the expressions of inflammatory cytokines in CRC mice, including down-regulation of IL1a, IL6, IL12a, IL12b, IL17a, and elevation of IL10. These cytokines were positively correlated with Azospirillum_sp._47_25, Clostridium_sensu_stricto_1, the E. coli complex, Akkermansia, Turicibacter, and negatively correlated with Muribaculum, Anaeroplasma, Candidatus_Arthromitus, and Candidatus Saccharimonas. Furthermore, the repressed expressions of TGFb, STAT3 and elevated expressions of TNFa, IFNg, CXCR4 together promoted the anti-cancer efficacy. Their expressions were positively correlated with Odoribacter, Lachnospiraceae-UCG-006, Desulfovibrio, and negatively correlated with Alloprevotella, Ruminococcaceae UCG-014, Ruminiclostridium, Prevotellaceae UCG-001 and Oscillibacter. Our studies indicate that FMT inhibits the development of CRC by reversing gut microbial disorder, ameliorating excessive intestinal inflammation and cooperating with anti-cancer immune responses.
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Wireless power transfer (WPT) is an essential enabler for novel sensor networks such as the wireless powered communication network (WPCN). The efficiency of an energy rectifier is dependent on both input power and loading condition. In this work, to maximize the rectifier efficiency, we present a low-complexity numerical method based on an analytical rectifier model to calculate the optimal load for different rectifier topologies, including half-wave and voltage-multipliers, without needing time-consuming simulations. The method is based on a simplified analytical rectifier model based on the diode equivalent circuit including parasitic parameters. Furthermore, by using Lambert-W function and the perturbation method, closed-form solutions are given for low-input power cases. The method is validated by means of both simulations and measurements. Extensive transient simulation results using different diodes (Skyworks SMS7630 and Avago HSMS285x) and frequency bands (400 MHz, 900 MHz, and 2.4 GHz) are provided for validation of the method. A 400 MHz 1- and 2-stage voltage multiplier are designed and fabricated, and measurements are conducted. Different input signals are used when validating the proposed methods, including the single sinewave signal and the multisine signal. The proposed numerical method shows excellent accuracy with both signal types, as long as the output voltage ripple is sufficiently low.
RESUMO
OBJECTIVES: Vancomycin resistance in Enterococcus spp., mediated mainly by the vanA resistance gene, has become a major health concern as it has spread worldwide. Therefore, a rapid method is urgently required to detect the vanA gene for timely and appropriate antimicrobial control of resistant Enterococcus infections. METHODS: The loop-mediated isothermal amplification (LAMP) assay was optimised for vanA detection in Enterococcus spp. isolates. RESULTS: The LAMP primer set designed in this study could reliably recognise seven distinct regions of the vanA gene and amplify the gene within 25min at an isothermal temperature of 65°C with high specificity. The sensitivity of the optimised assay was high, with a detection limit for vanA as low as 100pg/µL, which is 100-fold more sensitive than the PCR assay. A special advantage of this optimised LAMP method is that the vanA gene could be detected directly from clinical specimens. CONCLUSION: This optimised LAMP assay has great application potential for efficient detection of vanA in clinical diagnosis and epidemiological studies.
Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Carbono-Oxigênio Ligases/genética , Enterococcus faecalis/efeitos dos fármacos , Enterococcus faecalis/genética , Enterococcus faecium/efeitos dos fármacos , Enterococcus faecium/genética , Técnicas de Amplificação de Ácido Nucleico , Adolescente , Adulto , Enterococcus faecalis/isolamento & purificação , Enterococcus faecium/isolamento & purificação , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Temperatura , Resistência a Vancomicina/genética , Adulto JovemRESUMO
Macrolide-streptogramin type B resistance (the MSB phenotype) is a multidrug resistance phenotype in Staphylococcus aureus conferred by the resistance gene msrA. However, bacteria having the MSB phenotype are susceptible to lincosamides and 16-membered ring macrolides, which makes profiling resistance genes necessary and urgent for timely and appropriate use of antimicrobials. In this study, the loop-mediated isothermal amplification (LAMP) assay was optimized for prompt detection of the msrA gene. msrA gene sequences were obtained from the National Center for Biotechnology Information (NCBI) database and primers were designed using the LAMP primer designing software PrimerExplorer v.4, which together recognize seven distinct regions of the msrA gene. The specific LAMP primer set designed in this study could amplify the msrA gene within 25min at an isothermal temperature of 62°C. More importantly, the msrA gene could be detected at a sensitivity as low as 100pg. Furthermore, this optimized LAMP assay provided swift detection of the msrA gene even directly from human specimens. In conclusion, this assay may have great clinical application potential for detection of the msrA gene.