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1.
Mol Med Rep ; 25(1)2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34859260

RESUMO

Among the different types of oral cancer, >90% of cases are oral squamous cell carcinoma (OSCC). 5­fluorouracil (5­FU) is a commonly used treatment for OSCC, but cells typically display resistance to the drug. Propofol, an intravenous anesthetic agent, exhibits certain anticancer effects, including the inhibition of cancer cell proliferation, migration and invasion. Secreted proteins, such as growth factors and cytokines are involved in cancer development and progression, but the effect of propofol on secreted proteins in OSCC is not completely understood. An MTT assay, flow cytometry and western blotting were performed to determine the anticancer effects of propofol. The secretion profile of OSCC was determined using an antibody array, and clinical importance was assessed using the Gene Expression Profiling Interactive Analysis database. The results were verified by performing reverse transcription­quantitative PCR (RT­qPCR) and western blotting. 5­FU­resistant cells were established to determine the role of the gene of interest in drug resistance. The results demonstrated that propofol decreased cell viability and promoted cell apoptosis. The antibody array results showed that propofol attenuated the secretion of multiple growth factors. The bioinformatics results indicated that amphiregulin (AREG) was expressed at significantly higher levels in cancer tissues, which was also related to poor prognosis. The results of RT­qPCR and western blotting revealed that propofol decreased AREG expression. Pretreatment with exogenous recombinant AREG increased EGFR activation and conferred propofol resistance. Moreover, the results indicated that the expression and activation of AREG was also related to 5­FU resistance, but propofol ameliorated 5­FU drug resistance. Therefore, the present study suggested that propofol combination therapy may serve as an effective treatment strategy for OSCC.

2.
Anticancer Res ; 41(12): 6123-6133, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34848467

RESUMO

BACKGROUND/AIM: Urothelial carcinoma (UC) is the most common type of genitourinary cancer with high incidence and mortality rates in men. In this study, we used the BFTC-905 and T24 bladder cancer cell lines as in vitro models to investigate the pathways involved in flaccidoxide-induced apoptosis. MATERIALS AND METHODS: We utilized MTT assays, colony assays, wound-healing assays and fluorescence with TUNEL to confirm the cytotoxicity of flaccidoxide in bladder cancer cell lines. Potential proliferative and apoptotic molecular mechanisms were evaluated by western blotting. RESULTS: The expression of anti-apoptotic proteins Bcl-2 and phosphorylated Bad (p-Bad) was attenuated with an increasing flaccidoxide concentration, while the expression of proapoptotic proteins Bax, Bad, cleaved caspase-3, cleaved caspase-9 and cleaved PARP-1 was found increased. Additionally, phosphorylation of phosphoinositide 3-kinases (PI3K), protein kinase B (AKT) and mammalian target of rapamycin (mTOR) in the PI3K/AKT/mTOR pathway was reduced, leading to a reduction in the phosphorylation of downstream 70-kDa ribosomal protein S6 kinase 1 (p70S6K), S6 ribosomal protein (S6) and eukaryotic translation initiation factor 4B (eIF4B). However, eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) protein phosphorylation was increased due to attenuation of the upstream phosphorylation of mTOR protein. CONCLUSION: Flaccidoxide-induced apoptosis in BFTC-905 and T24 cells is mediated by mitochondrial dysfunction and down-regulation the PI3K/AKT/mTOR/p70S6K signaling pathway.

3.
Rev Sci Instrum ; 92(11): 113702, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34852563

RESUMO

In ultrashort pulse laser applications, optical dispersion seriously affects the energy concentration in the laser pulse duration and lowers the peak power. Accordingly, this study proposes a rapid dispersion estimation mechanism to facilitate the compensation of optical dispersion using a closed-loop control system. In the proposed approach, the optical dispersion information of the laser pulse is estimated directly from a frequency-resolved optical gating trace without the need for an iterative pulse-retrieval algorithm. In particular, the group delay dispersion (GDD) is determined from frequency and delay marginals, which are related to the laser spectrum and intensity autocorrelation, respectively, using a simple lookup table approach. The accuracy of the estimated GDD results is confirmed via a comparison with the spectral phase distribution of the electric field reconstructed using the principal component generalized projections algorithm. It is shown that the computation time of the proposed direct estimation method is around 13 times faster than that of the traditional iterative algorithm. It thus provides a feasible approach for enabling the real-time compensation of ultrafast laser pulse compression. Moreover, in a multiphoton-excited fluorescence imaging application, the proposed pulse compression mechanism yields an effective improvement in the intensity and contrast of the reconstructed image due to the increased nonlinear optical excitation efficiency of the optimized laser pulses.

4.
Adv Healthc Mater ; : e2102271, 2021 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-34855279

RESUMO

Macrophages settle in heterogeneous microenvironments consisting of soluble or fixed biochemical components and biophysical clues rendered by other cells and extracellular matrices. It is well known that chemical stimuli direct macrophage behavior; however, the contributions of viscosity, which increase in inflammatory tissues but not in tumors, are ignored in related immune responses including effective activation and timely attenuation. This paper demonstrates that transient lipopolysaccharide (LPS)-treated macrophages benefit from elastic substrates, whereas viscoelastic substrates with similar storage moduli support the inflammatory responses of macrophages under persistent stimulations and consequently amplify the distinctions between the transient and persistent LPS-induced transcriptional programs. Actin filaments (F-actin), direct responders to mechanical stimulations, fluctuate in line with transcriptional profiles and can be mathematically predicted by a clutch-like model. Moreover, viscosity modifies immune responses through transcription factors NF-κB and C/EBPδ, which act as switches discriminating between the transient and persistent infections. Interestingly, enhanced immune responses, consistent with the lower activated states, are attenuated in a timely manner by the actin nucleation-related translocation of ATF3 to nuclei. These findings suggest that the substrate viscoelasticity induces more intense inflammation only in the case of persistent infection and serves as a key module for perceiving the duration of infection more sensitively through the F-actin correlated transcription factors. In addition, it may facilitate cognition of immune response in inflammatory and cancerous microenvironments and have a wide range of applications in inflammatory regulations. This article is protected by copyright. All rights reserved.

5.
Front Plant Sci ; 12: 756557, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34858460

RESUMO

The Chinese wheat landrace "Gaoxianguangtoumai" (GX) has exhibited a high level of adult-plant resistance (APR) to stripe rust in the field for more than a decade. To reveal the genetic background for APR to stripe rust in GX, a set of 249 F6:8 (F6, F7, and F8) recombinant inbred lines (RILs) was developed from a cross between GX and the susceptible cultivar "Taichung 29." The parents and RILs were evaluated for disease severity at the adult-plant stage in the field by artificial inoculation with the currently predominant Chinese Puccinia striiformis f. sp. tritici races during three cropping seasons and genotyped using the Wheat 55K single-nucleotide polymorphism (SNP) array to construct a genetic map with 1,871 SNP markers finally. Two stable APR quantitative trait loci (QTL), QYr.GX-2AS and QYr.GX-7DS in GX, were detected on chromosomes 2AS and 7DS, which explained 15.5-27.0% and 11.5-13.5% of the total phenotypic variation, respectively. Compared with published Yr genes and QTL, QYr.GX-7DS and Yr18 may be the same, whereas QYr.GX-2AS is likely to be novel. Haplotype analysis revealed that QYr.GX-2AS is likely to be rare which presents in 5.3% of the 325 surveyed Chinese wheat landraces. By analyzing a heterogeneous inbred family (HIF) population from a residual heterozygous plant in an F8 generation of RIL, QYr.GX-2AS was further flanked by KP2A_36.85 and KP2A_38.22 with a physical distance of about 1.37Mb and co-segregated with the KP2A_37.09. Furthermore, three tightly linked Kompetitive allele-specific PCR (KASP) markers were highly polymorphic among 109 Chinese wheat cultivars. The results of this study can be used in wheat breeding for improving resistance to stripe rust.

6.
Microb Genom ; 7(12)2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34860152

RESUMO

Meromictic lakes usually harbour certain prevailing anoxygenic phototrophic bacteria in their anoxic zone, such as the purple sulfur bacterium (PSB) Thiocapsa sp. LSW (hereafter LSW) in Lake Shunet, Siberia. PSBs have been suggested to play a vital role in carbon, nitrogen and sulfur cycling at the oxic-anoxic interface of stratified lakes; however, the ecological significance of PSBs in the lake remains poorly understood. In this study, we explored the potential ecological role of LSW using a deep-sequencing analysis of single-cell genomics associated with flow cytometry. An approximately 2.7 Mb draft genome was obtained based on the co-assembly of five single-cell genomes. LSW might grow photolithoautotrophically and could play putative roles not only as a carbon fixer and diazotroph, but also as a sulfate reducer/oxidizer in the lake. This study provides insights into the potential ecological role of Thiocapsa sp. in meromictic lakes.

7.
BMC Bioinformatics ; 22(1): 548, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34758735

RESUMO

BACKGROUND: Discerning genes crucial to antimicrobial resistance (AMR) mechanisms is becoming more and more important to accurately and swiftly identify AMR pathogenic strains. Pangenome-wide association studies (e.g. Scoary) identified numerous putative AMR genes. However, only a tiny proportion of the putative resistance genes are annotated by AMR databases or Gene Ontology. In addition, many putative resistance genes are of unknown function (termed hypothetical proteins). An annotation tool is crucially needed in order to reveal the functional organization of the resistome and expand our knowledge of the AMR gene repertoire. RESULTS: We developed an approach (PangenomeNet) for building co-functional networks from pan-genomes to infer functions for hypothetical genes. Using Escherichia coli as an example, we demonstrated that it is possible to build co-functional network from its pan-genome using co-inheritance, domain-sharing, and protein-protein-interaction information. The investigation of the network revealed that it fits the characteristics of biological networks and can be used for functional inferences. The subgraph consisting of putative meropenem resistance genes consists of clusters of stress response genes and resistance gene acquisition pathways. Resistome subgraphs also demonstrate drug-specific AMR genes such as beta-lactamase, as well as functional roles shared among multiple classes of drugs, mostly in the stress-related pathways. CONCLUSIONS: By demonstrating the idea of pan-genome-based co-functional network on the E. coli species, we showed that the network can infer functional roles of the genes, including those without functional annotations, and provides holistic views on the putative antimicrobial resistomes. We hope that the pan-genome network idea can help formulate hypothesis for targeted experimental works.


Assuntos
Infecções por Escherichia coli , Escherichia coli , Antibacterianos/farmacologia , Escherichia coli/genética , Infecções por Escherichia coli/tratamento farmacológico , Humanos , beta-Lactamases/genética
8.
Can J Infect Dis Med Microbiol ; 2021: 8518189, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777671

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is a disease caused by infection with the SFTS virus (SFTSV). SFTS has become a crucial public health concern because of the heavy burden, lack of vaccines, effective therapies, and high-fatality rate. Evidence suggests that SFTSV circulates between ticks and animals in nature and is transmitted to humans by tick bites. In particular, ticks have been implicated as vectors of SFTSV, where domestic or wild animals may play as the amplifying hosts. Many studies have identified antigens and antibodies against SFTSV in various animals such as sheep, goats, cattle, and rodents. Besides, person-to-person transmission through contact with blood or mucous of an infected person has also been reported. In this study, we reviewed the literature and summarized the vectors and hosts associated with SFTS and the possible risk factors.

9.
J Palliat Care ; : 8258597211051208, 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34787527

RESUMO

Objective: The Advance Care Planning Engagement Survey (ACP-ES) has proven effective in evaluating individuals' engagement in advance care planning (ACP). However, a Traditional Chinese version of ACP-ES (ACPES-TC) has not yet been developed. Therefore, this study aimed to translate and preliminarily validate the ACPES-TC in the Taiwanese context. Material and Methods: A forward and backward translation process was conducted. The translated questionnaire was confirmed by clinical and academic experts. The ACPES-TC was then evaluated for its reliability and validity with participants in the community and from an outpatient clinic in a medical center in Northern Taiwan. The participants comprised healthy people aged 20 to 30 years and patients ≥55 years old, recruited from September 17 to October 28, 2019. Results: Seventy people were recruited, including 20 people aged 20 to 30 years in the community and 50 patients ≥ 55 years old from clinics. The ACPES-TC scores are significantly higher among those of older age, having financial independence, and under long-term medication (p < .05). The patients' preference for health-related decision-making is significantly correlated with the ACPES-TC score; the point-biserial correlation coefficient is 0.46 (p < .001). The discriminant and criterion-related validities are verified. The ACPES-TC demonstrated a good internal consistency (Cronbach's α .97), acceptable one-week test-retest reliability (overall intraclass correlation coefficient 0.86), and low practice effect between the test and retest (Cohen's d .43). Conclusion: The overall reliability and validity of the ACPES-TC are fair, which could be used to evaluate the patients' engagement in ACP in Taiwan. However, further studies with a full-scale psychometric evaluation are needed.

10.
Sensors (Basel) ; 21(21)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34770526

RESUMO

Numerous studies indicated the physical benefits of regular exercise, but the neurophysiological mechanisms of regular exercise in elders were less investigated. We aimed to compare changes in brain activity during exercise in elderly people and in young adults with and without regular exercise habits. A total of 36 healthy young adults (M/F:18/18) and 35 healthy elderly adults (M/F:20/15) participated in this study. According to exercise habits, each age group were classified into regular and occasional exerciser groups. ECG, EEG, and EMG signals were recorded using V-AMP with a 1-kHz sampling rate. The participants were instructed to perform three 5-min bicycle rides with different exercise loads. The EEG spectral power of elders who exercised regularly revealed the strongest positive correlation with their exercise intensity by using Pearson correlation analysis. The results demonstrate that exercise-induced significant cortical activation in the elderly participants who exercised regularly, and most of the p-values are less than 0.001. No significant correlation was observed between spectral power and exercise intensity in the elders who exercised occasionally. The young participants who exercised regularly had greater cardiac and neurobiological efficiency. Our results may provide a new exercise therapy reference for adult groups with different exercise habits, especially for the elders.


Assuntos
Exercício Físico , Hábitos , Idoso , Nível de Saúde , Humanos , Adulto Jovem
11.
Artigo em Inglês | MEDLINE | ID: mdl-34761429

RESUMO

OBJECTIVE: To explore the association between obesity and precocious puberty from the perspective of genetic polymorphism. DESIGN: Two hundred and ninety-eight pairs of girls in early puberty and age-matched controls (±3 months) were recruited. The genotypes of four obesity-related single-nucleotide polymorphism (SNP) loci (rs10968576, rs12935153, rs4674340 and rs7635103) were determined and the effect of variation on early puberty in Chinese Han girls was evaluated. The unstimulated luteinizing hormone (LH), follicle-stimulating hormone and estradiol levels were also measured to determine the relationship with SNP polymorphisms. RESULTS: The effect allele A of rs12935153 was associated with early puberty (odds ratio [OR] = 1.256, 95% confidence interval [CI]: 1.010-1.585), but the significance disappeared after multiple comparisons. After adjusting for body mass index, rs12935153 variation increased the risk of early puberty in additive (OR = 1.589, 95% CI: 1.222-2.066), dominant (OR = 1.788, 95% CI: 1.210-2.642) and recessive (OR = 1.915, 95% CI: 1.207-3.038) models of inheritance. Individuals harbouring AA genotype in rs12935153 had a risk of higher LH levels than that of wild type (OR = 1.668, 95% CI: 1.093-2.546). CONCLUSIONS: The association between obesity and precocity can be explained from a genetic perspective. Our study suggests that variations in rs12935153 increase the risk of early puberty in Chinese girls. Further studies are needed to verify our findings.

12.
Artigo em Inglês | MEDLINE | ID: mdl-34761489

RESUMO

The clinic prospect of sonodynamic therapy (SDT) has not been fully realized due to the scarcity of efficient sonosensitizers. Herein, we designed phthalocyanine-artesunate conjugates (e.g. ZnPcT 4 A), which could generate up to ca. 10-fold more reactive oxygen species (ROS) than the known sonosensitizer protoporphyrin IX. Meanwhile, an interesting and significant finding of aggregation-enhanced sonodynamic activity (AESA) was observed for the first time. ZnPcT 4 A showed about 60-fold higher sonodynamic ROS generation in aggregation form than disaggregation form in aqueous solutions. That could be attributed to the boosted ultrasonic cavitation of nanostructures. The levels of AESA effect depended on the aggregation ability of sonosensitizer molecules and the particle sizes of their aggregates. Moreover, biological studies demonstrated that ZnPcT 4 A had high anticancer activities and biosafety. This study thus opens up a new avenue the development of efficient organic sonosensitizers.

14.
Zhongguo Gu Shang ; 34(10): 978-84, 2021 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-34726029

RESUMO

OBJECTIVE: To explore the effects of siRNA hsa-circ-0000885 modified bone marrow mesenchymal stem cells (BMSCs) on osteogenic differentiation, cell proliferation and apoptosis in order to provide new ideas and methods for the clinical treatment of osteoporosis (OP). METHODS: From September 2018 to February 2020, 13 patients with osteoporosis admitted to our hospital were selected as the research objects, including 11 females and 2 males, with an age of (65.45±10.77) years old. After obtaining the informed consent of patients, peripheral blood tissues were extracted. Then the expression level of cir-cRNA in peripheral blood mononuclear cells(PBMC) was detected by circ RNA chip. The expression of circ RNA was silenced by siRNA technology. The BMSCs were transfected with lentivirus. According to the siRNA interference plasmid hsa-circ-0000885, the cells were divided into the blank group, the empty vector group and the siRNA interference group. After 72 hours of treatment, the cell cycle was detected by flow cytometry, the apoptosis level was detected by AV-PI kit, and the osteogenic differentiation ability of BMSCs was detected by ALP staining. RESULTS: The expression of hsa-circ-0000885 in PBMC of patients with osteoporosis was significantly higher than that of healthy controls (t=2.119, P<0.05). ALP staining showed that siR-NA hsa-circ-0000885 could promote the osteogenic differentiation of BMSCs, which was obviously too much in the blank group and blank plasmid group (F=9.132, q=2.995, 2.897;P=0.009, 0.012<0.05). The results of CCK-8 showed that siRNA hsa-circ-0000885 could promote the proliferation of BMSCs, which was significantly higher than that of the blank group and blank plasmid group (F=9.881, q=2.457, 2.904;P=0.032, 0.016<0.05). The results of AV-PI showed that the apoptosis rate of siRNA interference group was significantly lower than that of blank group and blank plasmid group(F=10.208;q=2.885, 3.001; P=0.019, 0.011<0.05). CONCLUSION: The lentivirus mediated siRNA hsa-circ-0000885 plasmid transfected into BMSCs and osteoclast co culture system can promote cell proliferation, inhibit apoptosis and promote osteogenic differentiation of BMSCs, which can be used as a potential therapeutic target for OP patients.


Assuntos
Leucócitos Mononucleares , Células-Tronco Mesenquimais , Idoso , Apoptose/genética , Diferenciação Celular , Proliferação de Células/genética , Células Cultivadas , Técnicas de Cocultura , Feminino , Humanos , Lentivirus , Pessoa de Meia-Idade , Osteoclastos , Osteogênese/genética , RNA Interferente Pequeno/genética , Transfecção
15.
Front Cardiovasc Med ; 8: 731844, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722665

RESUMO

Backgrounds: Influenza vaccination could decrease the risk of major cardiac events in patients with chronic obstructive pulmonary disease (COPD). However, the effects of the vaccine on decreasing the risk of ventricular arrhythmia (VA) development in such patients remain unclear. Methods: We retrospectively analyzed the data of 18,658 patients with COPD (≥55 years old) from the National Health Insurance Research Database from January 1, 2001, to December 31, 2012. After a 1:1 propensity score matching by the year of diagnosis, we divided the patients into vaccinated and unvaccinated groups. Time-varying Cox proportional hazards regression was applied to assess the time to event hazards of influenza vaccination exposure. Results: The risk of VA occurrence was significantly lower in the vaccinated group during influenza season and all seasons [adjusted hazard ratio (aHR): 0.62, 95% CI: 0.41-0.95; aHR: 0.69, 95% CI: 0.44-1.08; and aHR: 0.65, 95% CI: 0.48-0.89, in the influenza season, non-influenza season, and all seasons, respectively]. Among patients with CHA2DS2-VASc scores (conditions and characteristics included congestive heart failure, hypertension, diabetes, stroke, vascular disease, age, and sex) of 2-3, receiving one time and two to three times of influenza vaccination were associated with lower risk of VA occurrence in all seasons (aHR: 0.28, 95% CI: 0.10-0.80; aHR: 0.27, 95% CI: 0.10-0.68, respectively). Among patients without stroke, peripheral vascular disease, and diabetes, a lower risk of VA occurrence after receiving one and two to three times vaccination was observed in all seasons. Among patients with a history of asthma and patients without a history of heart failure, ischemic heart disease, angina hypertension, or renal failure, a significantly lower risk of VA occurrence was observed after the first time of vaccination in all seasons. Conclusions: Influenza vaccination may be associated with lower risks of VA among patients with COPD aged 55-74. Further investigation is still needed to resolve this clinical question.

17.
Risk Manag Healthc Policy ; 14: 4477-4488, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34754254

RESUMO

Purpose: This study aimed to assess the knowledge, attitude and practice (KAP) towards COVID-19 of Chinese college students during the COVID-19 outbreak and identify the determinants considerably associated with KAP. Methods: An online cross-sectional questionnaire survey was conducted in February 2020 in China to recruit participants on the Wen-Juan-Xing online platform. A self-made questionnaire was used to assess the KAP towards COVID-19. Results: The average scores of COVID-19-related KAP among college students were 32.16 ± 4.09, 16.84 ± 3.18 and 15.36 ± 1.83, respectively. The average correct response rate of COVID-19-related knowledge was 84.62%. 94.59% of the respondents believed China could control and conquer the pandemic; 98.92% of the respondents wore a mask when they went out. The multiple linear regression showed that the female students had higher scores of COVID-19-related knowledge than male students (ß = 0.79, P = 0.01), and the students from 985 or 211 universities (ß = -2.22, P < 0.01) were significantly associated with higher knowledge scores. Furthermore, a significantly positive correlation was found between the scores of COVID-19-related KAP among students. Conclusion: The college students had a good KAP towards the COVID-19 pandemic. The present study was able to access the COVID-19-related KAP among college students during the pandemic and identify their weaknesses in pandemic prevention. Consequently, the results of this study provide theoretical basis for implementing precision health education among college students and reference for campuses to conduct scientific prevention and control during a pandemic. Results also provide beneficial experience to curb similar major public health emergencies in the future.

18.
Front Physiol ; 12: 729925, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34744770

RESUMO

Background: Neuron apoptosis, regulated by endoplasmic reticulum (ER) stress in the hippocampus, is an essential factor influencing the cognitive impairment induced by hypobaric hypoxia. Hypoxia mainly changes the activating transcription factor (ATF6) pathway of ER stress. However, the role of ATF6 in neuron survival, apoptosis, and upstream regulation is still controversial. Methods: We established a hypobaric hypoxia-induced C57BL/6 murine model and cell lines exposed to 1% hypoxia, including PC12 and HT22. First, we tested the expressions of interleukin 6 (IL-6), IL-1ß, and IL-10 in C57BL/6 mice's hippocampus under hypoxia using enzyme-linked immunosorbent assay (ELISA). We determined the signal transducer and activator of transcription 3 (STAT3) phosphorylation at tyrosine (Tyr)705 by western blot and the expression of ATF6, 78-kDa glucose-regulated protein (GRP78), and C/-EBP homologous protein (CHOP) related to ER stress by immunofluorescence (IF), western blot, and qRT-PCR; they were then verified on the cell model. Additionally, IL-6 (40 ng/mL) and STAT3 siRNA were used to treat the PC12 cells for 48 and 4 h to activate or silence STAT3, respectively. Subsequently, the cells of siRNA group were exposed to 1% hypoxia for 48 h. Furthermore, the ATF6 and CHOP expressions were detected with western blot and qRT-PCR. Finally, we examined the binding of STAT3 to the ATF6 promoter by chromatin immunoprecipitation (ChIP)-seq. Results: The results showed that IL-6 increased, IL-10 decreased in the hypoxia group, and IL-1ß showed no difference between the hypoxia and the normoxia groups. Neuron apoptosis was significantly elevated by exposure to hypoxia for 48h in PC12 cells. The hypobaric hypoxia-induced ER stress proteins, ATF6, GRP78, and CHOP, and the p-STAT3 (Tyr705) expressions increased both in in vivo and in vitro. Besides, STAT3 silencing significantly promoted the ATF6 expression and inhibited CHOP, while STAT3 activation downregulated the expression of ATF6 and upregulated CHOP in PC12 cells. The ChIP-seq assay demonstrated that p-STAT3 (Tyr705) protein could bind to the ATF6 promoter region in HT22 cells. Conclusion: Phosphorylation of STAT3 at the Tyr705 site contributes to hypoxia-induced neuron apoptosis by downregulating ATF6, which might explain the inflammatory reaction and apoptosis of the hippocampal neurons induced by ER stress.

19.
Injury ; 2021 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-34756739

RESUMO

BACKGROUND: For patients sustaining major trauma, preinjury warfarin use may make adequate haemostasis difficult. This study aimed to determine whether preinjury warfarin would result in more haemostatic interventions (transarterial embolization [TAE] or surgeries) and a higher failure rate of nonoperative management for blunt hepatic, splenic or renal injuries. METHODS: This was a retrospective cohort study from the Taiwan National Health Insurance Research Database (NHIRD) from 2003 to 2015. Patients with hepatic, splenic or renal injuries were identified. The primary outcome measurement was the need for invasive procedures to stop bleeding. One-to-two propensity score matching (PSM) was used to minimize selection bias. RESULTS: A total of 37,837 patients were enrolled in the study, and 156 (0.41%) had preinjury warfarin use. With proper 1:2 PSM, patients who received warfarin preinjury were found to require more haemostatic interventions (39.9% vs. 29.1%, p=0.016). The differences between the two study groups were that patients with preinjury warfarin required more TAE than the controls (16.3% vs 8.2%, p = 0.009). No significant increases were found in the need for surgeries (exploratory laparotomy (5.2% vs 3.6%, p = 0.380), hepatorrhaphy (9.2% vs 7.2%, p = 0.447), splenectomy (13.1% vs 13.7%, p = 0.846) or nephrectomy (2.0% vs 0.7%, p = 0.229)). Seven out of 25 patients (28.0%) in the warfarin group required further operations after TAE, which was not significantly different from that in the nonwarfarin group (four out of 25 patients, 16.0%, p = 0.306) CONCLUSION: Preinjury warfarin increases the need for TAE but not surgeries. With proper haemostasis with TAE and resuscitation, nonoperative management can still be applied to patients with preinjury warfarin sustaining blunt hepatic, splenic or renal injuries. Patients with preinjury warfarin had a higher risk for surgery after TAE.

20.
Zhongguo Zhong Yao Za Zhi ; 46(19): 4936-4944, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34738387

RESUMO

In this study, liquid chromatography-mass spectrometry(LC-MS) and high performance liquid chromatography(HPLC) were employed for qualitative and quantitative analysis of the steroidal saponins in rhizomes of Paris polyphylla var. yunnanensis from three different habitats cultured in vitro, in an attempt to explore whether the rhizomes of the medicinal herb cultured in vitro can synthesize the steroidal saponins, including polyphyllinsⅠ, Ⅱ, and Ⅶ, the quality markers specified in Chinese Pharmacopoeia(2020 edition). A total of 20 steroidal saponins were identified in the rhizomes from Changxin, Yunlong(S1), Fengyi, Dali(S2), and Niujie, Eryuan(S3): parisyunnanoside A and parisyunnanoside D or E, proto-polyphyllin Ⅱ, polyphyllins G and H, polyphyllinsⅠ, Ⅱ, Ⅴ, Ⅵ, and Ⅶ, dioscin, gracillin, prosapogenin A, Tg, isomer of Th, saponin Th, reclinatoside, proto-pairs D, pseudoproto-dioscin, and 23-O-glc-(23S,25R)-spirost-5-en-3ß,23α,27-triol-3-O-rha-(1→2)-[ara(1→4)]-glc or 27-O-glc-(23S,25R)-spirost-5-en-3ß,27α-diol-3-O-rha-(1→2)-[ara(1→4)]-glc. Among them, polyphyllinsⅠ, Ⅱ, and Ⅶ were detected in the rhizomes from S1, with the mass fraction of 0.109 1%, 0.165 2%, and 0.051 03%, respectively(total 0.325 3%). Polyphyllins Ⅱ and Ⅶ were identified in the rhizomes from S2 with the respective mass fraction of 0.192 2% and 0.074 23% and total content of 0.266 5%. Moreover, polyphyllins Ⅱ and Ⅶ were also found in the rhizomes from S3, which had the mass fraction of 0.207 7% and 0.186 9%, separately, with the total content of 0.394 6%. Thus, steroidal saponins, including the quality makers polyphyllins Ⅰ, Ⅱ, and Ⅶ recorded in Chinese Pharmacopoeia(2020 edition) can be synthesized in rhizomes of Paris polyphylla var. yunnanensis cultured in vitro, but their total content fails to meet the standard(0.60% in Chinese Pharmacopoeia). Therefore, in vitro culture of the Paris polyphylla var. yunnanensis is feasible, but the culture conditions need to be further improved.


Assuntos
Liliaceae , Melanthiaceae , Saponinas , Cromatografia Líquida de Alta Pressão , Rizoma
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