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BACKGROUND: Highly reactive oxygen species (ROS) could lead to serious damage in living cells and are associated with many diseases like cancers. Metal cluster with strong fluorescence has great potential in biosensing and many thiolate ligands-protected clusters have been applied in ROS sensing. RESULTS: In this work, we synthesized levonorgestrel protected Au10 cluster with specific sensing ability for highly ROS via crystal transformation from Au8 cluster, demonstrating the significance of inner core structure on detecting performance. The detection limit of Au10 cluster for ClO- could reach as low as 0.1 µM. This fluorescent probe not only achieving detection of exogenous ClO- in living cells and zebrafish, but also successful imaging of endogenous ClO- in HeLa and HepG2 cells. SIGNIFICANCE: In comparison to previously reported cluster-based sensors for ROS, this work proposes a different reaction mechanism of metal nanoclusters for ROS detection (breakage of gold-alkynyl bond and oxidation of alkynyl group). This provides new directions for designing specific ROS probes and broadens the applications of metal clusters in disease diagnostics.
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Colorantes Fluorescentes , Oro , Ácido Hipocloroso , Levonorgestrel , Pez Cebra , Humanos , Oro/química , Células HeLa , Ácido Hipocloroso/análisis , Animales , Células Hep G2 , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Levonorgestrel/química , Imagen Óptica , Especies Reactivas de Oxígeno/metabolismo , Especies Reactivas de Oxígeno/análisis , Nanopartículas del Metal/químicaRESUMEN
OBJECTIVE: To explore the mechanism of electroacupunctureï¼EAï¼ in improving learning-memory ability in Alzheimer's disease ï¼ADï¼ mice from the perspective of endosomal-lysosomal system. METHODS: Male APP/PS1 transgenic mice were randomly divided into model group and EA group ï¼n=10 in each groupï¼ and 10 male C57BL/6 wild mice were taken as the normal group. EA ï¼1 Hz/50 Hz, 1 mAï¼ was applied at bilateral "Yongquan"ï¼KI1ï¼ and acupuncture was applied at "Baihui" ï¼GV20ï¼ for 15 min. The mice of the model and normal groups were subjected to restriction with the same method as those of the EA group for 15 min. The treatment was conducted once every other day for 6 weeks. The spatial learning-memory ability ï¼shown by escape latency of place navigation test and the time of crossing the target platform and total swimming distance in the target quadrant in 1 min of spatial probe test ï¼ was detected by Morris water maze test. The immunoactivity of senile plaques ï¼SPï¼ in the hippocampus tissue was detected by immunohistochemistry. The ultrastructural characters of hippocampal neurons were observed by transmission electron microscope, and the expression levels of Ras-related protein 5 ï¼Rab5ï¼, Ras-related protein 7 ï¼Rab7ï¼ and cathepsin D ï¼CTSDï¼ in the hippocampus were detected by Western blot, separately. RESULTS: Compared with the normal group, the escape latency, SP immunoactivity, and protein expression levels of Rab5, Rab7 and CTSD were significantly increased ï¼P<0.05, P<0.01ï¼, while the number of crossing the original platform and the total swimming distance in the platform quadrant were considerably reduced ï¼P<0.05ï¼ in the model group. In contrast to the model group, the EA group had a marked decrease in the escape latency, SP immunoactivity, and protein expression levels of Rab5, Rab7 and CTSD ï¼P<0.05, P<0.01ï¼, and a striking increase in the number of crossing the original platform and the swimming distance in the platform quadrant ï¼P<0.05ï¼. Results of transmission electron microscope showed an accumulation of endosome, lysosome, and endolysosomes in the hippocampal neurons in the model group, which was evidently milder in the EA group. CONCLUSION: EA of GV20 and KI1 can improve the learning-memory ability of AD mice, which may be related to its function in reducing hippocampal Aß deposition and down-regulating endosomal-lysosomal system activity.
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Enfermedad de Alzheimer , Electroacupuntura , Masculino , Ratones , Animales , Ratones Endogámicos C57BL , Ratones Transgénicos , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/terapia , Endosomas , Lisosomas/genética , Placa AmiloideRESUMEN
In this study, an overview of systematic reviews/Meta-analysis(SR/MA) of Chinese herbal injections for sepsis was performed to provide references for clinical practice and promote the quality improvement of clinical evidence. Eight Chinese and English databases such as CNKI, Medline, and EMbase were electronically searched for SR/MA of Chinese herbal injections for sepsis from database inception to June 2022. AMSTAR 2, PRISMA 2020, and GRADE system, combined with Recommendations for Clinical Evidence Grading on Traditional Chinese Medicine Based on Evidence Body, were applied to evaluate the methodological quality, reporting quality, and evidence quality of the included articles. Twenty-seven articles of SR/MA were included, containing four Chinese herbal injections(Xuebijing Injection, Shenfu Injection, Shenmai Injection, and Shengmai Injection). AMSTAR 2 checklist showed that the methodological quality of the SR/MA ranged from moderate to very low. Item 2(prior study design) was the critical item with poor scores, and the non-critical items with poor scores were items 3(explain the selection of the study designs), items 10(report on the sources of funding), and items 16(conflicts of interest stated). In terms of PRISMA 2020, items in eight topics with complete reporting of missing>50%, including search strategy, certainty assessment, results of syntheses, certainty of evidence, registration and protocol, support, competing interests, availability of data, code and other materials. The included SR/MA involved 30 outcome indicators. Evidence quality of mortality, APACHE â ¡, and safety, the top three outcome indicators, was evaluated, and all of them were graded as the medium level. The lack of random allocation sequence, allocation concealment mechanism, blinding, and trial sample size was the main reason for the reduction of the evidence level. The available evidence shows that Chinese herbal injections can serve as an effective and safe adjunctive treatment for sepsis, which can reduce mortality, inhibit inflammation, improve coagulation function, and regulate immune function, tissue perfusion, and oxygenation in patients with sepsis. However, the quality of SR/MA was suboptimal, and more high-quality SR/MA is needed to provide evidence to support the efficacy and safety of Chinese herbal injections in the treatment of sepsis.
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Medicina Tradicional China , Sepsis , Humanos , Inyecciones , Proyectos de Investigación , Sepsis/tratamiento farmacológicoRESUMEN
OBJECTIVE: To investigate the effect of electroacupuncture (EA) on the expression of ß-amyloid (Aß) and autophagy-related proteins in hippocampal cells of Alzheimer's disease (AD) model mice, so as to explore its underlying mechanisms. METHODS: Eighteen male APP/PS1 transgenic mice (6 months old) were randomly divided into model and EA groups, with 9 mice in each group. Nine male C57BL/6 wild-type mice of the same age were chosen as the normal group. Mice in the EA group were treated with acupuncture on "Baihui" (GV20) and EA (1 Hz/50 Hz, 1 mA) on bilateral "Yongquan" (KI1), once every other day, 20 min each time for a total of 21 times. After the interventions, the spatial learning and memory ability were observed by Morris water maze test. The autophagy-related pathological changes in hippocampus were observed by transmission electron microscopy. The expressions of microtublue associated protein 1 light chain 3 (LC3) and Aß in hippocampus were observed by immunofluorescence and the expression levels of LC3 and p62 proteins were detected by Western blot. RESULTS: Compared with the normal group, the escape latency was prolonged (P<0.01), the residence time in the original quadrant platform was shor-tened (P<0.05), the positive expressions of LC3 and Aß, the expression levels of LC3â ¡ and p62 proteins, and the ratio of LC3â ¡/LC3â proteins in hippocampus were increased (P<0.01, P<0.05) in the model group. Compared with the model group, the escape latency was shortened (P<0.05), the residence time in the original quadrant platform was prolonged (P<0.05), the positive expressions of LC3 and Aß, the expression levels of LC3â ¡ and p62 proteins, and the ratio of LC3â ¡/LC3â proteins in hippocampus were decreased (P<0.05) in the EA group. The transmission electron microscopy showed that the structure of neurons was normal in the normal group, a large number of autolysosomes and autophagosomes existed in hip-pocampal nerve cells in the model group, and only a small number of autophagosomes were observed in the EA group. CONCLUSION: EA can reduce the expression levels of autophagy-related proteins LC3 and p62 in APP/PS1 transgenic mice, improve the hip-pocampal autophagy state, reduce intracellular Aß aggregation, and thus improve the learning and memory ability.
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Enfermedad de Alzheimer , Electroacupuntura , Ratones , Masculino , Animales , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/terapia , Péptidos beta-Amiloides/genética , Péptidos beta-Amiloides/metabolismo , Proteínas Relacionadas con la Autofagia/metabolismo , Ratones Endogámicos C57BL , Hipocampo/metabolismo , Ratones Transgénicos , Aprendizaje EspacialRESUMEN
BACKGROUND: COVID-19 has posed an enormous threat to public health around the world. Some severe and critical cases have bad prognoses and high case fatality rates, unraveling risk factors for severe COVID-19 are of significance for predicting and preventing illness progression, and reducing case fatality rates. Our study focused on analyzing characteristics of COVID-19 cases and exploring risk factors for developing severe COVID-19. METHODS: The data for this study was disease surveillance data on symptomatic cases of COVID-19 reported from 30 provinces in China between January 19 and March 9, 2020, which included demographics, dates of symptom onset, clinical manifestations at the time of diagnosis, laboratory findings, radiographic findings, underlying disease history, and exposure history. We grouped mild and moderate cases together as non-severe cases and categorized severe and critical cases together as severe cases. We compared characteristics of severe cases and non-severe cases of COVID-19 and explored risk factors for severity. RESULTS: The total number of cases were 12 647 with age from less than 1 year old to 99 years old. The severe cases were 1662 (13.1%), the median age of severe cases was 57 years [Inter-quartile range(IQR): 46-68] and the median age of non-severe cases was 43 years (IQR: 32-54). The risk factors for severe COVID-19 were being male [adjusted odds ratio (aOR) = 1.3, 95% CI: 1.2-1.5]; fever (aOR = 2.3, 95% CI: 2.0-2.7), cough (aOR = 1.4, 95% CI: 1.2-1.6), fatigue (aOR = 1.3, 95% CI: 1.2-1.5), and chronic kidney disease (aOR = 2.5, 95% CI: 1.4-4.6), hypertension (aOR = 1.5, 95% CI: 1.2-1.8) and diabetes (aOR = 1.96, 95% CI: 1.6-2.4). With the increase of age, risk for the severity was gradually higher [20-39 years (aOR = 3.9, 95% CI: 1.8-8.4), 40-59 years (aOR = 7.6, 95% CI: 3.6-16.3), ≥ 60 years (aOR = 20.4, 95% CI: 9.5-43.7)], and longer time from symtem onset to diagnosis [3-5 days (aOR = 1.4, 95% CI: 1.2-1.7), 6-8 days (aOR = 1.8, 95% CI: 1.5-2.1), ≥ 9 days(aOR = 1.9, 95% CI: 1.6-2.3)]. CONCLUSIONS: Our study showed the risk factors for developing severe COVID-19 with large sample size, which included being male, older age, fever, cough, fatigue, delayed diagnosis, hypertension, diabetes, chronic kidney diasease, early case identification and prompt medical care. Based on these factors, the severity of COVID-19 cases can be predicted. So cases with these risk factors should be paid more attention to prevent severity.
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Factores de Edad , COVID-19/epidemiología , Comorbilidad , Índice de Severidad de la Enfermedad , Factores Sexuales , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Preescolar , China/epidemiología , Diagnóstico Precoz , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Factores de Riesgo , Adulto JovenRESUMEN
During our systematic study on the anticancer activities of Scutellaria barbata, scutebarbatine A (SBT-A), one of the major alkaloids in S. barbata, was found to have antitumor effects on A549 cells. Thus, we designed the present study to investigate in detail the antitumor effects of SBT-A. The cytotoxic effect of SBT-A on A549 in vitro were determined by an MTT assay and evaluated by IC50 values. Furthermore, results of Hoechst 33258 and Annexin V/PI staining assays demonstrated that SBT-A had significant antitumor effects on A549 cells via apoptosis, in a concentration-dependent manner. What's more, the mechanism was explored by western blotting, and our study revealed that SBT-A can up-regulate the expressions of cytochrome c, caspase-3 and 9, and down-regulate the levels of Bcl-2 in A549 cells. Finally, the antitumor effects of SBT-A were evaluated in vivo by using transplanted tumor nude mice, and the results confirmed that SBT-A has a notable antitumor effect on A549 cancer via mitochondria-mediated apoptosis. Collectively, our results demonstrated that SBT-A showed significant antitumor effects on A549 cells in vivo and in vitro via mitochondria-mediated apoptosis by up-regulating expressions of caspase-3 and 9, and down-regulating Bcl-2.
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Antineoplásicos Fitogénicos/farmacología , Naftoles/farmacología , Niacina/farmacología , Animales , Apoptosis , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Forma de la Célula , Humanos , Ratones Desnudos , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
This study was designed to evaluate the anticonvulsant and sedative effects of paederosidic acid isolated from Paederia scandens (Lour.) Merrill. in mice and rats. In the present study, anticonvulsant activities of paederosidic acid were evaluated by maximal electroshock and pentylenetetrazole-induced seizures in male mice. Then, pentobarbital sodium-induced sleeping time and locomotor activity tests in mice were used to evaluate the sedative effects of paederosidic acid. Finally, the mechanism of paederosidic acid was explored by evaluating the contents of Glu and GABA in the brain, and Western blot was used to measure GAD65 expression in the mouse brain. Paederosidic acid (5, 10, 20, and 40 mg/kg, ip) had significant anticonvulsant and sedative effects. Moreover, paederosidic acid increased brain gamma-aminobutyric acid and decreased glutamic acid in the brain, and it up-regulated expressions of GAD 65. In conclusion, our results suggest that paederosidic acid may be a promising future therapeutic agent for treatment of epilepsy.