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1.
Polymers (Basel) ; 14(9)2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35566938

RESUMO

Enzymatic preparation of low-molecular-weight chondroitin sulfate (LMWCS) has received increasing attention. In this work, a chondroitin sulfate lyase ABC (Chon-ABC) was successfully cloned, expressed, and characterized. The Km and Vmax of the Chon-ABC were 0.54 mM and 541.3 U mg-1, respectively. The maximal activity was assayed as 500.4 U mg-1 at 37 °C in pH 8.0 phosphate buffer saline. The half-lives of the Chon-ABC were 133 d and 127 min at 4 °C and 37 °C, respectively. Enzymatic preparation of LMWCS was performed at room temperature for 30 min. The changes between the substrate and product were analyzed with mass spectrometry (MS), high-performance liquid chromatography (HPLC), gel permeation chromatography (GPC), and nuclear magnetic resonance (NMR). Overall, the Chon-ABC from Bacteroides thetaiotaomicron is competitive in large-scale enzymatic preparation of LMWCS for its high activity, stability, and substrate specificity.

2.
Artigo em Inglês | MEDLINE | ID: mdl-35575049

RESUMO

The lifespan of practical lithium (Li) metal batteries is severely hindered by the instability of Li metal anodes. Fluorinated solid electrolyte interphase (SEI) emerges as a promising strategy to improve the stability of Li metal anodes. The rational design of fluorinated molecules is pivotal to constructing fluorinated SEI. Herein, design principles of fluorinated molecules are proposed. Fluoroalkyl (-CF2CF2-) is selected as an enriched F reservoir and the defluorination of C-F bond is driven by leaving groups on ß-site. An activated fluoroalkyl molecule (AFA), 2,2,3,3-tetraflurobutane-1,4-diol dinitrate is unprecedentedly proposed to render fast and complete defluorination and generate uniform fluorinated SEI on Li metal anodes. In Li-sulfur (Li-S) batteries under practical conditions, the fluorinated SEI constructed by AFA undergoes 183 cycles, which is three times of the SEI formed by LiNO3. Furthermore, a Li-S pouch cell of 360 Wh kg-1 delivers 25 cycles with AFA. This work demonstrates rational molecular design principles of fluorinated molecules to construct fluorinated SEI for practical Li metal batteries.

3.
Ying Yong Sheng Tai Xue Bao ; 33(4): 1027-1036, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35543056

RESUMO

We examined the effects of biochar and urease inhibitors/nitrification inhibitors on nitrification process, ammonia and N2O emission in subtropical soil, and determined the best combination of biochar with nitrification and urease inhibitors. This work could provide a theoretical basis for the mitigation of the negative environmental risk caused by reactive nitrogen gas in the application of nitrogen fertilizer. A indoor aerobic culture test was conducted with seven treatments [urea+biochar (NB), urea+nitrification inhibitor (N+NI), urea+urease inhibitor (N+UI), urea+nitrification inhibitor+urease inhibitor (N+NIUI), urea+nitrification inhibitor+biochar (NB+NI), urea+urease inhibitor+biochar (NB+UI), urea+nitrification inhibitor+urease inhibitor+biochar (NB+NIUI)] and urea (N) as the control. The dynamics of soil inorganic nitrogen content, N2O emission and the volatility of ammonia volatilization were observed under combined application of biochar with urease inhibitor (NBPT)/nitrification inhibitor (DMPP). The results showed that:1)Compared to the control (5.11 mg N·kg-1·d-1) during the incubation period, NB treatment significantly increased therate constant of nitrification by 33.9%, and N+NI treatment significantly reduced the nitrification rate constant by 22.9%. NB treatment significantly increased the abundance of ammonia oxidizing bacteria (AOB) by 56.0%. 2) Compared with N treatment, N+NI and NB+NI treatments signi-ficantly enhanced the cumulative emission of NH3 by 49%. The N+UI treatment reduced the cumulative loss of NH3. The inhibition effect of NB+UI treatment was more significant. 3) The emission rate of N2O was highest in the first 10 days after fertilization. The N2O emission under NB treatment was the earliest, and that of N treatment was the highest (5.87 µg·kg-1·h-1). The combined application of DMPP and NBPT performed the best in reducing soil N2O emission. We estimated global warming potential (GWP) of the direct N2O and indirect N2O (NH3) emissions. Compared with N treatments, N+NI and NB+NI treatments increased the GWP by 34.8% and 40.9%, respectively. While the NB and NB+UI treatments significantly reduced the GWP by 45.9% and 60.5%, the combination of biochar and urease inhibitor had the best effect on reduction of GWP of soil active nitrogen emissions.


Assuntos
Nitrificação , Solo , Agricultura/métodos , Amônia/análise , Carvão Vegetal , Iodeto de Dimetilfenilpiperazina/farmacologia , Fertilizantes/análise , Nitrogênio/análise , Óxido Nitroso/análise , Ureia , Urease
4.
Cancer Res ; 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35544764

RESUMO

Micropeptides are a recently discovered class of molecules that play vital roles in various cellular processes, including differentiation, proliferation, and apoptosis. Here, we sought to identify cancer-associated micropeptides and to uncover their mechanistic functions. A micropeptide named short trans-membrane protein 1 (STMP1) that localizes at the inner mitochondrial membrane was identified to be upregulated in various cancer types and associated with metastasis and recurrence of hepatocellular carcinoma. Both gain- and loss-of-function studies revealed that STMP1 increased dynamin-related protein 1 (DRP1) activation to promote mitochondrial fission and enhanced migration of tumor cells. STMP1 silencing inhibited in vivo tumor metastasis in xenograft mouse models. Overexpression of STMP1 led to redistribution of mitochondria to the leading edge of cells and enhanced lamellipodia formation. Treatment with a DRP1 inhibitor abrogated the promotive effect of STMP1 on mitochondrial fission, lamellipodia formation, and tumor cell migration in vitro and metastasis in vivo. Furthermore, STMP1 interacted with myosin heavy chain 9 (MYH9), the subunit of non-muscle myosin II, and silencing MYH9 abrogated STMP1-induced DRP1 activation, mitochondrial fission, and cell migration. Collectively, this study identifies STMP1 as a critical regulator of metastasis and a novel unit of the mitochondrial fission protein machinery, providing a potential therapeutic target for treating metastases.

5.
BMC Genomics ; 22(Suppl 5): 919, 2022 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-35534820

RESUMO

BACKGROUND: Alternative splicing (AS) increases the diversity of transcriptome and could fine-tune the function of genes, so that understanding the regulation of AS is vital. AS could be regulated by many different cis-regulatory elements, such as enhancer. Enhancer has been experimentally proved to regulate AS in some genes. However, there is a lack of genome-wide studies on the association between enhancer and AS (enhancer-AS association). To bridge the gap, here we developed an integrative analysis on a genome-wide scale to identify enhancer-AS associations in human and mouse. RESULT: We collected enhancer datasets which include 28 human and 24 mouse tissues and cell lines, and RNA-seq datasets which are paired with the selected tissues. Combining with data integration and statistical analysis, we identified 3,242 human and 7,716 mouse genes which have significant enhancer-AS associations in at least one tissue. On average, for each gene, about 6% of enhancers in human (5% in mouse) are associated to AS change and for each enhancer, approximately one gene is identified to have enhancer-AS association in both human and mouse. We found that 52% of the human significant (34% in mouse) enhancer-AS associations are the co-existence of homologous genes and homologous enhancers. We further constructed a user-friendly platform, named Visualization of Enhancer-associated Alternative Splicing (VEnAS, http://venas.iis.sinica.edu.tw/ ), to provide genomic architecture, intuitive association plot, and contingency table of the significant enhancer-AS associations. CONCLUSION: This study provides the first genome-wide identification of enhancer-AS associations in human and mouse. The results suggest that a notable portion of enhancers are playing roles in AS regulations. The analyzed results and the proposed platform VEnAS would provide a further understanding of enhancers on regulating alternative splicing.


Assuntos
Processamento Alternativo , Elementos Facilitadores Genéticos , Animais , Estudo de Associação Genômica Ampla , Genômica/métodos , Humanos , Camundongos , RNA-Seq
6.
Artigo em Inglês | MEDLINE | ID: mdl-35502176

RESUMO

Materials and Methods: The active compounds in DO, their targets, and targets associated with hyperlipidemia were screened across various databases, and the hidden targets of DO in treating hyperlipidemia were forecast. The compound-target (C-T), protein-protein interaction (PPI), and compound-target-pathway (C-T-P) networks of DO were set up with Cytoscape software. The hub genes and core clusters of DO predicted to be active against hyperlipidemia were calculated by Cytoscape. The DAVID database was adopted for Gene Ontology (GO) analysis and KEGG pathway enrichment analysis. Next, we used the high-sucrose-fat diet and alcohol (HFDA)-induced hyperlipidemia rats to evaluate the hypolipidemic effect of DO. Results: In this study, we obtained 264 compounds from DO, revealed 11 bioactive compounds, and predicted 89 potential targets of DO. The network analysis uncovered that naringenin, isorhamnetin, and taxifolin might be the compounds in DO that are mainly in charge of its roles in hyperlipidemia and might play a role by modulating the targets (including PPARG, ADIPOQ, AKT1, TNF, and APOB). The pathway analysis showed that DO might affect diverse signaling pathways related to the pathogenesis of hyperlipidemia, including PPAR signaling pathway, insulin resistance, AMPK signaling pathway, and non-alcoholic fatty liver disease simultaneously. Meanwhile, in the HFDA-induced hyperlipidemia rat model, DO could significantly decrease the level of TC, TG, LDL-c, and ALT in serum, and increase HDL-c as well. The liver pathological section indicated that DO could ease liver damage and lipid cumulation. Conclusion: In summary, the biological targets of the main bioactive compounds in DO were found to distribute across multiple metabolic pathways. These findings suggest that a mutual regulatory system consisting of multiple components, targets, and pathways is a likely mechanism through which DO may improve hyperlipidemia. Validation experiments indicated that DO may treat hyperlipidemia by affecting NAFLD-related signaling pathways.

7.
Front Cell Dev Biol ; 10: 883266, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35531096

RESUMO

Matrix-metalloproteinase-13 (MMP13) is important for bone formation and remodeling; however, its role in tooth development remains unknown. To investigate this, MMP13-knockout (Mmp13 -/- ) mice were used to analyze phenotypic changes in the dentin-pulp complex, mineralization-associated marker-expression, and mechanistic interactions. Immunohistochemistry demonstrated high MMP13-expression in pulp-tissue, ameloblasts, odontoblasts, and dentin in developing WT-molars, which reduced in adults, with human-DPC cultures demonstrating a >2000-fold increase in Mmp13-expression during mineralization. Morphologically, Mmp13 -/- molars displayed critical alterations in the dentin-phenotype, affecting dentin-tubule regularity, the odontoblast-palisade and predentin-definition with significantly reduced dentin volume (∼30% incisor; 13% molar), and enamel and dentin mineral-density. Reactionary-tertiary-dentin in response to injury was reduced at Mmp13 -/- molar cusp-tips but with significantly more dystrophic pulpal mineralization in MMP13-null samples. Odontoblast differentiation-markers, nestin and DSP, reduced in expression after MMP13-loss in vivo, with reduced calcium deposition in MMP13-null DPC cultures. RNA-sequencing analysis of WT and Mmp13 -/- pulp highlighted 5,020 transcripts to have significantly >2.0-fold change, with pathway-analysis indicating downregulation of the Wnt-signaling pathway, supported by reduced in vivo expression of the Wnt-responsive gene Axin2. Mmp13 interaction with Axin2 could be partly responsible for the loss of odontoblastic activity and alteration to the tooth phenotype and volume which is evident in this study. Overall, our novel findings indicate MMP13 as critical for tooth development and mineralization processes, highlighting mechanistic interaction with the Wnt-signaling pathway.

8.
Zhongguo Zhong Yao Za Zhi ; 47(7): 1857-1863, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35534255

RESUMO

This study aims to establish a method for determination of paeonol(Pae), eugenol(Eug), and piperine(Pip) content in receptor liquid and research on the permeability and pharmacokinetics of Huoxue Zhitong gel patch and microemulsion gel. The Franz diffusion experiment was conducted to assess the percutaneous permeability, and the microdialysis method was employed to assess pharmacokinetics of Huoxue Zhitong gel patch and microemulsion gel. The content of Pae, Eug, and Pip in receptor liquid in vitro and in vivo was determined by HPLC and UPLC-MS. The Q_n and J_(ss) of Pae, Eug, and Pip in the gel patch were significantly higher than those in the microemulsion gel, indicating that the drug release was faster in the gel patch. The C_(max), AUC_(0-760), and MRT of Pae, Eug, and Pip in the gel patch were higher than those in the microemulsion gel, indicating that the gel patch can promote the penetration and prolong the skin residence of the drug. The results of this study provide reference for improving the dosage form of Huoxue Zhitong patch.


Assuntos
Absorção Cutânea , Espectrometria de Massas em Tandem , Administração Cutânea , Cromatografia Líquida , Emulsões , Permeabilidade , Pele/metabolismo
9.
Nucleic Acids Res ; 2022 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-35536289

RESUMO

With the proliferation of genomic sequence data for biomedical research, the exploration of human genetic information by domain experts requires a comprehensive interrogation of large numbers of scientific publications in PubMed. However, a query in PubMed essentially provides search results sorted only by the date of publication. A search engine for retrieving and interpreting complex relations between biomedical concepts in scientific publications remains lacking. Here, we present pubmedKB, a web server designed to extract and visualize semantic relationships between four biomedical entity types: variants, genes, diseases, and chemicals. pubmedKB uses state-of-the-art natural language processing techniques to extract semantic relations from the large number of PubMed abstracts. Currently, over 2 million semantic relations between biomedical entity pairs are extracted from over 33 million PubMed abstracts in pubmedKB. pubmedKB has a user-friendly interface with an interactive semantic graph, enabling the user to easily query entities and explore entity relations. Supporting sentences with the highlighted snippets allow to easily navigate the publications. Combined with a new explorative approach to literature mining and an interactive interface for researchers, pubmedKB thus enables rapid, intelligent searching of the large biomedical literature to provide useful knowledge and insights. pubmedKB is available at https://www.pubmedkb.cc/.

10.
Ecotoxicol Environ Saf ; 239: 113664, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35605331

RESUMO

Neuroinflammation is a key mechanism underlying the cognitive impairment induced by PM2.5, and activated microglia plays an important role in this process. However, the mechanisms by which activated microglia induced by PM2.5 impair hippocampal neurons have not been fully elucidated. In this study, we focused on the role of HMGB1-NLRP3-P2X7R pathway which mediated the microglia activation in hippocampal neurons impairment induced by PM2.5 using a co-culture model of microglia and hippocampal neurons. We found that PM2.5 resulted in activated microglia and HMGB1-NLRP3 inflammatory pathway, and elevated proinflammatory cytokines of IL-18 and IL-1ß in a dose-dependent manner. Notably, we next utilized previously reported pharmacological inhibitors or siRNA for HMGB1 and found that they significantly inhibited the activation of downstream NLRP3 and MAPK pathways derived from PM2.5 exposure, and down-regulated IL-18 and IL-1ß in microglia. Furthermore, we employed co-cultured hippocampal neurons and microglia and found that reducing HMGB1 significantly decreased neuron impairment, apoptosis related protein of cl-caspase3, synaptic damage, and neurotransmitter receptor of 5-HT2A, along with notably elevated presynaptic and postsynaptic proteins of SYP and PSD-95, as well as learning and memory related proteins of p-CREB and BDNF. The neuronal impairment induced by PM2.5 could not be prevented in the case of simultaneous employment of HMGB1 siRNA and NLRP3 agonist. After silencing NLRP3 alone in microglia, hippocampal neurons demonstrated decreased excessive autophagy and up-regulated synaptic protein of GAP43 as well as learning and memory related protein of NCAM1. Therefore, we further studied how hippocampal neurons affected microglia under PM2.5 exposure, Further investigation indicated that silencing HMGB1 could affect the activation of P2X7R and reduce the release of ATP from hippocampal neurons, thus protecting the interaction between microglia and hippocampal neurons. The present work suggests that regulation of HMGB1-NLRP3-P2X7R pathway can inhibit the microglia activation induced by PM2.5 to alleviate hippocampal neuron impairment and stabilize the microenvironment between microglia and neurons. This contributes to maintaining the normal function of hippocampal neurons and alleviating the cognitive impairment derived from PM2.5 exposure.

11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 39(5): 468-473, 2022 May 10.
Artigo em Chinês | MEDLINE | ID: mdl-35598259

RESUMO

OBJECTIVE: To analyze the genomic variation characteristics of fetal with abnormal serological screening, and to further explore the value of copy number variation (CNV) detection technology in prenatal diagnosis of fetal with abnormal serological screening. METHODS: 7617 singleton pregnant women who underwent amniocentesis for prenatal diagnosis solely due to abnormal Down's serological screening were selected. According to the results of serological screening, the patients were divided into high risk group, borderline risk group and single abnormal multiple of median (MOM) group. CMA and CNV-Seq were used to detect the copy number variation of amniotic fluid cell genomic DNA and combined with amniotic fluid cell karyotype analysis for prenatal diagnosis. Outpatient revisit combined with telephone inquiry was used for postnatal follow-up. RESULTS: Among 7617 amniotic fluid samples, aneuploidy was detected in 138cases (1.81%) by CMA and CNV-Seq, 9 cases of aneuploid chimerism were detected by amniotic fluid cell karyotype analysis, and 203 cases of fetus carrying pathogenic and likely pathogenic CNV (P/LP CNV) were detected, the variant of uncertain significance (VUS) was detected in 437 cases (5.7%), the overall abnormal detection rate was 10.33%. The detection rate of aneuploidy by CMA and CNV-Seq in three group were 123 cases (2.9%), 13 cases (1.3%) and 2 cases (0.4%), respectively,and showing no significant difference (χ 2=7.469, P=0.024). The detection rate of pathogenic and likely pathogenic CNV in three group were 163cases (2.6%); 24 cases (2.6%) and 16 cases (3.3%), respectively, and showing no significant difference (χ 2=0.764, P=0.682). The CMA reported 2.9% (108/3729)P/LP CNV, and CNV-seq reported 2.4% (95/3888)P/LP CNV, both tests showed similar detective capabilities (χ 2=1.504, P=0.22).The most popular P/LP CNV in this cohort were Xp22.31 microdeletion, 16p13.11 microduplication /microdeletion, 22q11.21 microduplication /microdeletion. In fetuses with P/LP CNV CNV, 59 fetuses were terminated pregnancy, and 32 of 112 fetuses born had abnormal clinical manifestations. Non-medically necessary termination of pregnancy occurred in 11 fetuses carrying VUS CNV, 322 fetuses carrying VUS CNV were born, 4 of them presented abnormal clinical manifestations. CONCLUSION: Compared with the traditional chromosome karyotype, CMA and CNV-Seq can improve the detection rate of pathogenic and likely pathogenic CNV. CMA and CNV-seq can be used for first tier diagnosis of pregnant women in the general population with abnormal Down's serological screening.


Assuntos
Variações do Número de Cópias de DNA , Gestantes , Líquido Amniótico , Aneuploidia , Aberrações Cromossômicas , Feminino , Genômica , Humanos , Gravidez , Segundo Trimestre da Gravidez , Diagnóstico Pré-Natal/métodos , Tecnologia
12.
Nutrients ; 14(9)2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35565813

RESUMO

Mother and newborn skin-to-skin contact (SSC) after birth has numerous protective effects. Although positive associations between SSC and breastfeeding behavior have been reported, the evidence for such associations between early SSC and breastfeeding success was limited in high-income countries. This quasi-experimental intervention design study aimed to evaluate the impact of different SSC regimens on newborn breastfeeding outcomes in Taiwan. In total, 104 healthy mother-infant dyads (52 in the intervention group and 52 in the control group) with normal vaginal delivery were enrolled from 1 January to 30 July 2019. The intervention group received 60 min of immediate SSC, whereas the control group received routine care (early SSC with 20 min duration). Breastfeeding performance was evaluated by the IBFAT and BSES-Short Form. Generalized estimating equations (GEEs) were used to evaluate the effectiveness of the intervention. In the intervention group, the breastfeeding ability of newborns increased significantly after 5 min of SSC and after SSC. The intervention also improved the total score for breastfeeding self-efficacy (0.18 point; p = 0.003). GEE analysis revealed that the interaction between group and time was significant (0.65 point; p = 0.003). An initial immediate SSC regimen of 60 min can significantly improve neonatal breastfeeding ability and maternal breastfeeding self-efficacy in the short term after birth.

13.
J Vis Exp ; (183)2022 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-35575526

RESUMO

As microbes that thrive in the host body primarily have adaptive abilities that facilitate their survival, methods for classifying and identifying their nature would be beneficial in facilitating their characterization. Currently, most studies focus only on one specific characterization method; however, the isolation and identification of microorganisms from the host is a continuous process and usually requires several combinatorial characterization methods. Herein, we describe methods of identifying the microbial biofilm-forming ability, the microbial respiration state, and their chemotaxis behavior. The methods are used to identify five microbes, three of which were isolated from the bone tissue of Sprague-Dawley (SD) rats (Corynebacterium stationis, Staphylococcus cohnii subsp. urealyticus, and Enterococcus faecalis) and two from the American Type Culture Collection (ATCC)-Staphylococcus aureus ATCC 25923 and Enterococcus faecalis V583. The microbes isolated from the SD rat bone tissue include the gram-positive microbes. These microbes have adapted to thrive under stressful and nutrient-limiting environments within the bone matrix. This article aims to provide the readers with the specific know-how of determining the nature and behavior of the isolated microbes within a laboratory setting.

14.
J Psychiatr Res ; 151: 286-290, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35525230

RESUMO

This study was to investigate the relationship between the ventral caudate connectivity and anhedonia. Nineteen depressed patients and 16 healthy controls participated in two identical functional magnetic resonance imaging scans during a 1-year period to determine the resting-state functional connectivity changes using a seed-based approach. Patients showed increased left ventral caudate functional connectivity with superior frontal gyrus over time and the increased connectivity was associated with anhedonia improvement. None of these associations were observed in healthy controls. The findings suggest that left ventral caudate may serve as a potential target to improve the severity of anhedonia.

15.
J Ethnopharmacol ; 294: 115353, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35533911

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Marsdenia tenacissima is a medicinal plant, used as a raw material for cancer treatment in China. In our previous studies, 11α-O-2-methylbutanoyl-12ß-O-tigloyl-tenacigenin B (MT2), the main steroid aglycone isolated from M. tenacissima, was found to significantly enhance the antitumor activity of paclitaxel (PTX) in vivo. However, it is unclear whether MT2 reverses multidrug resistance (MDR) in tumors. AIM OF THE STUDY: To determine the role and mechanism of MT2 in reversing tumor MDR. MATERIALS AND METHODS: MDR cell line HeLa/Tax was established from the human cervical carcinoma cell line HeLa by long-term exposure to subtoxic concentrations of PTX and was used to evaluate the ability of MT2 to restore chemosensitivity of cells both in vitro and in a nude mouse model. The expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (MRP2) was determined using western blotting and immunohistochemistry. The substrate transport function was assessed using an MDR function assay kit. The binding modes of MT2 and P-gp were determined using the conformation-sensitive anti-P-gp antibodies. The permeability and transport properties of MT2 were analyzed in Caco-2 cell monolayers. RESULTS: Compared to parental cells, HeLa/Tax cells overexpress P-gp and MRP2 and are approximately 100-360 fold more resistant to the anticancer drugs PTX, docetaxel, and vinblastine. MT2 at 5 or 10 µmol/L significantly increased the sensitivity of HeLa/Tax to these three anticancer drugs (18-56-fold decrease in IC50 value) and suppressed the expression of P-gp and MRP2. Knockdown of P-gp with small interfering RNA partially reversed MT2-induced sensitivity to PTX in HeLa/Tax cells. Moreover, MT2 directly inhibited P-gp-mediated substrate transport while interacting with membrane P-gp in non-substrate ways. MT2 was highly permeable and could not be transported in the Caco-2 cell monolayers. In nude mice bearing HeLa/Tax xenografts, the combination treatment with MT2 and PTX exerted a synergistic inhibitory effect on the growth of tumors and the expression of P-gp and MRP2 without increasing toxicity. CONCLUSION: MT2 is a potential agent for reversing MDR. It impedes membrane drug efflux pumps by suppressing P-gp and MRP2 expression, and directly inhibiting the transport function of P-gp.

16.
Endocr J ; 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35431280

RESUMO

Recent studies have found compared with insulin glargine (IGlar), insulin degludec/aspart (IDeg/Asp) may provide adequate glycemic control and prevent hypoglycemia events in type 2 diabetes mellitus (T2DM). Consequently, we performed a meta-analysis to appraise and compare the efficiency and safety of IDeg/Asp and IGlar in the treatment of T2DM. We sought the databases including PubMed, Embase, Scopus, Cochrane library to confirm related articles which inspected the effect of IDeg/Asp versus IGlar for the treatment of T2DM until May 2021. Finally, six randomized controlled trials (RCTs) of 1,346 patients were included. The results showed that IDeg/Asp significantly decreased the mean hemoglobin A1c (HbA1c) level but was prone to serious adverse events, and IGlar increased the nocturnal confirmed hypoglycemia events. Besides, there were no significant changes in other indicators, including mean fasting plasma glucose (FPG) level, nine-point self-measured plasma glucose (SMPG) level, and adverse events. What's more, we found that there was no significant difference in the occurrence of hypoglycemia overall, but our subgroup analysis of confirmed hypoglycemia revealed the population in this subgroup (duration of diabetes ≤11 years) might has its particularity effecting the hypoglycemia outcome. Concerning efficiency, IDeg/Asp may have advantages in controlling the mean HbA1c level. Regarding safety, IGlar might increase the risk of nocturnal confirmed hypoglycemia. Further evidence is needed to compare better the efficiency and safety of IDeg/Asp versus IGlar therapy.

17.
Front Genet ; 13: 828877, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35480310

RESUMO

Bufo bufo gargarizans Cantor are precious medicinal animals in traditional Chinese medicine (TCM). Bufadienolides as the major pharmacological components are generated from the venomous glands of B. bufo gargarizans. Bufadienolides are one type of cardiac aglycone with a six-member lactone ring and have properties of antitumor, cardiotonic, tonsillitis, and anti-inflammatory. The biosynthesis of bufadienolides is complex and unclear. This study explored the transcriptome of three different tissues (skin glands, venom glands, and muscles) of B. bufo gargarizans by high-throughput sequencing. According to the gene tissue-specific expression profile, 389 candidate genes were predicted possibly participating in the bufadienolides biosynthesis pathway. Then, BbgCYP11A1 was identified as a cholesterol side chain cleaving the enzyme in engineering yeast producing cholesterol. Furthermore, the catalytic activity of BbgCYP11A1 was studied with various redox partners. Interestingly, a plant NADPH-cytochrome P450 reductase (CPR) from Anemarrhena asphodeloides showed notably higher production than BbgAdx-2A-BbgAdR from B. bufo gargarizans. These results will provide certainly molecular research to reveal the bufadienolides biosynthesis pathway in B. bufo gargarizans.

18.
BMC Genomics ; 22(Suppl 5): 917, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35418014

RESUMO

BACKGROUND: Many long non-coding RNAs (lncRNAs) have been extensively identified in higher eukaryotic species. The function of lncRNAs has been reported to play important roles in diverse biological processes, including developmental regulation and behavioral plasticity. However, there are no reports of systematic characterization of long non-coding RNAs in the fire ant Solenopsis invicta. RESULTS: In this study, we performed a genome-wide analysis of lncRNAs in the brains of S. invicta from RNA-seq. In total, 1,393 novel lncRNA transcripts were identified in the fire ant. In contrast to the annotated lncRNA transcripts having at least two exons, novel lncRNAs are monoexonic transcripts with a shorter length. Besides, the transcriptome from virgin alate and dealate mated queens were analyzed and compared. The results showed 295 differentially expressed mRNA genes (DEGs) and 65 differentially expressed lncRNA genes (DELs) between virgin and mated queens, of which 17 lncRNAs were highly expressed in the virgin alates and 47 lncRNAs were highly expressed in the mated dealates. By identifying the DEL:DEG pairs with a high association in their expression (Spearman's |rho|> 0.8 and p-value < 0.01), many DELs were co-regulated with DEGs after mating. Furthermore, several remarkable lncRNAs (MSTRG.6523, MSTRG.588, and nc909) that were found to associate with particular coding genes may play important roles in the regulation of brain gene expression in reproductive transition in fire ants. CONCLUSION: This study provides the first genome-wide identification of S. invicta lncRNAs in the brains in different reproductive states. It will contribute to a fuller understanding of the transcriptional regulation underpinning reproductive changes.


Assuntos
Formigas , RNA Longo não Codificante , Animais , Formigas/genética , Encéfalo/metabolismo , Feminino , Perfilação da Expressão Gênica , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transcriptoma
19.
Insights Imaging ; 13(1): 65, 2022 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-35380293

RESUMO

BACKGROUND: Hepatic epithelioid hemangioendothelioma (HEH) is extremely rare and the MRI features have never been investigated in a large group of patients. METHODS: A retrospective study was designed to review the MRI images of HEH patients. Two radiologists separately evaluated signal intensity (SI) on unenhanced imaging, morphological features, contrast-enhancement pattern at dynamic study. The MRI features were compared between patients with HEH and hepatic metastatic tumor (HMT). RESULTS: Fifty-seven HEH patients were included in this study and a total of 412 lesions were evaluated. On per-lesion analysis, the rate of coalescent lesion and subcapsular lesion were 18.2% and 39.8%, respectively. Capsular retraction and lollipop sign were observed in 47 lesions (11.4%) and 60 lesions (14.6%), respectively. Large lesions (> 5 cm) had the highest rate of coalescent lesion, subcapsular lesion, capsular retraction and lollipop sign. Target sign appeared in 196 lesions (47.6%) on T2 weighted (T2W) and 146 lesions (35.4%) on portal phase. Medium lesions (2-5 cm) had the highest rate of target sign on both T2W (72.9%) and portal phase (55.2%). On per-patient analysis, compare with HEH patients, HMT patients seldom had the appearance of lollipop sign (66.7% versus 6.4%, p < 0.01), capsular retraction (59.6% versus 3.2%, p < 0.01) and target appearance on both T2Wand portal phase (64.9% versus 12.7%, p < 0.01). CONCLUSION: MRI features of HEH correlated with the lesion size. Capsular retraction, lollipop sign and coexistence of target sign on both T2W and portal phase were relatively specific MRI features of HEH, which could be helpful in suggesting the diagnosis.

20.
Comput Intell Neurosci ; 2022: 5509129, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432518

RESUMO

Dermatofibrosarcoma protuberans (DFSP) is a type of skin cancer that is extremely rare. Its standard treatment is either surgical wide-local excision (WLE) or Mohs micrographic surgery (MMS). Which method has the lowest recurrence rate is unknown. Dermatofibrosarcoma protuberans is an uncommon soft tissue sarcoma with a high propensity for recurrence. It has always remained a clinical challenge. More technology is needed to treat the disease. We reviewed our cases and published experience and evaluated whether 3D modeling could precisely define tumor morphological characteristics and assist excision in slow Mohs surgery. There were 18 dermatofibrosarcoma protuberan cases enrolled. They were treated in Shanghai Ninth People's Hospital from 2014 to 2019. All the 18 included patients presented with primary disease and no metastasis. All subjects had undergone thorough imaging examinations including CT and MRI. The 3D tumor reconstruction models were created for their tumors. We precisely estimated tumor boundaries and sizes according to those 3D models. Afterward, patients underwent slow Mohs surgery and surgical repair of tissue defects following tumor resection. The 3D tumor reconstruction models were successfully established. The predicted tumor volumes were measured in all 18 cases. The average volume was 38.5 cm3 (range: 8.4 cm3-183.6 cm3), which allowed for accurately locating the tumor. Tumors were completely removed in one stage of slow MMS surgery. In the second-stage surgery, the defects were repaired by different surgical methods including direct soft tissue closure, skin grafting, local flaps, or free flaps. Most patients experienced no significant complications. This practice indicated that the combination of a 3D reconstruction model and slow Mohs surgery achieves more precise and complete DFSP resection to decrease the recurrence rate.


Assuntos
Dermatofibrossarcoma , Cirurgia de Mohs , China , Dermatofibrossarcoma/patologia , Dermatofibrossarcoma/secundário , Dermatofibrossarcoma/cirurgia , Humanos , Imageamento Tridimensional , Cirurgia de Mohs/métodos , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia
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