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1.
Bioengineered ; 12(2): 9909-9917, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34860147

RESUMO

Colon cancer (CC), which has high morbidity and mortality, can be regulated by microRNAs. This study aimed to investigate the regulatory function of microRNA miR-145-5p in CC cells. Bioinformatics analysis was used to screen key genes in CC. The expression of miR-145-5p, chemokine (C-X-C motif) ligand 1 (CXCL1), and integrin α2 (ITGA2) in CC was confirmed by quantitative reverse transcription polymerase chain reaction and western blotting. After cell transfection, changes in proliferation and migration in CC cells were detected using the cell counting kit-8 (CCK-8), colony formation assay, and wound healing assay. A luciferase assay was conducted to confirm the interactome of miR-145-5p, CXCL1, and ITGA2 in CC cells. Bioinformatics analysis confirmed that CXCL1 and ITGA2 were key genes in CC. After performing several cell functional experiments, the results confirmed that upregulation of miR-145-5p attenuated proliferation and migration of CC cells. Luciferase assay and western blotting confirmed that CXCL1 and ITGA2 were targets of miR-145-5p, and their expression in CC could be suppressed by miR-145-5p. In conclusion, miR-145-5p is a tumor suppressor in CC and can inhibit the expression of CXCL1 and ITGA2.

2.
Int J Gen Med ; 14: 8455-8461, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34824544

RESUMO

Aim: To analyze the movement of anterior teeth by changing the height of the power-arm and changing the force application points during whole maxillary dentition distalization with the aid of micro-implants in lingual orthodontics to set a biomechanical reference for effective clinical use of lingual orthodontic appliance. Methods: A three-dimensional finite element model of the maxillary teeth with lingual appliance and the associated support tissue was established. Maxillary dentition with the force of 200g was distalized using implant as anchorage, then the movement of anterior teeth was analyzed by changing the length of power-arm (1mm, 3mm, 6mm, 9mm) and by changing the force location from lingual side to buccal side. Results: During whole maxillary dentition distalization with aid of the implants in lingual orthodontics: when the height of power arm was 1mm, the anterior teeth rotated clockwise, with the increasing of the height of power-arm, the anterior teeth rotated counterclockwise gradually. When the height of power-arm was 9mm, all anterior teeth rotated counterclockwise. Central incisor and lateral incisor rotated counterclockwise and canine rotated clockwise when the buccal side force was applied. Conclusion: With the increase of the height of the power-arm, the movement pattern of the upper anterior teeth is different. The canine is more sensitive to the height of the power-arm than the central incisor and the lateral incisor. When the height of the power-arm reaches 9mm, the upper anterior teeth are displayed as crown tipping buccally movement. Compare with lingual side force, the buccal side force do better in preventing the loss of anterior tooth torque. If the upper anterior teeth are up-right or lingually tipped before treatment, it is preferable to use longer power-arm or buccal side traction force. If the anterior teeth are already tipped buccally, then short power-arm or lingual side force is advised.

3.
Inflammation ; 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34786625

RESUMO

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS), characterized by demyelinating neuropathy. The etiology of MS is not yet clear and its treatment remains a major medical challenge. While we search for drugs that can effectively treat experimental autoimmune encephalomyelitis (EAE), the animal model of MS, we also hope to further explore its possible pathogenesis. In the present study, we investigated whether methyl butyrate (MB) could alleviate EAE and its potential mechanisms. In EAE mice, we found that administration of MB was effective in alleviating their clinical signs and improving histopathological manifestations of the CNS. In the CNS and intestinal lamina propria, we observed fewer effector T cells, including Th1 and Th17, in the MB-treated group. MB also increased the proportion of regulatory T cells and the secretion of IL-10 in peripheral immune organs. In vitro, MB led to suppression of Th1 cells and promotion of regulatory T cells in their differentiation. Given that MB had no direct effect on Th17 cell differentiation in vitro, we hypothesized that MB suppressed Th17 cells indirectly by inhibiting the secretion of IL-6, which was later confirmed both in vitro and in vivo. In addition, we found that MB treatment upregulated Maf gene expression in mice, which explained its promotion of IL-10 secretion. The above findings suggest that MB may provide new ideas for the study of the mechanism of MS and have positive implications for new drug development.

4.
Int Immunopharmacol ; : 108291, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34799286

RESUMO

Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system (CNS) mediated by immune cells. The pathogenesis of most autoimmune diseases has some degree of similarity to that of MS, and therefore the study of MS has clinical and scientific significance for other autoimmune diseases as well. As a widely used organic solvent, Methyl Acetate (MA) has a similar structure to acetate which has been shown to be therapeutic in the mouse model of multiple sclerosis. Here we found that MA was effective in reducing the disease severity of Experimental Autoimmune Encephalomyelitis (EAE). Pathological sections showed that MA reduced inflammatory cell infiltration in the CNS and attenuated demyelination in the spinal cord. MA increases the proportion of Th1 cells in the periphery of EAE mice. Further mechanistic studies have demonstrated that MA treatment induces Th1 retention in the peripheral immune system by increasing the expression levels of peripheral Th1-related chemokines CXCR3. CXCL9, CXCL10. In addition, we observed that MA alleviated intestinal inflammation in EAE mice. The data showed that this phenomenon is achieved by enhancing IL-10 and inhibiting IL-6 secretion. Our data indicates that MA might have therapeutic implications for autoimmune diseases such as MS.

5.
JACS Au ; 1(10): 1788-1797, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34723281

RESUMO

Picosecond fast motions and their involvement in the biochemical processes such as protein-ligand binding has engaged significant attention. Terahertz optical Kerr spectroscopy (OKE) has the superior potential to probe these fast motions directly. Application of OKE in protein-ligand binding study is, however, limited by the difficulty of quantitative atomistic interpretation, and the calculation of Kerr spectrum for entire solvated protein complex was considered not yet feasible, due to the lack of one consistent polarizable model for both configuration sampling and polarizability calculation. Here, we analyzed the biochemical relevance of OKE to the lysozyme-triacetylchitotriose binding based on the first OKE simulation using one consistent Drude polarizable model. An analytical multipole and induced dipole scheme was employed to calculate the off-diagonal Drude polarizability more efficiently and accurately. Further theoretical analysis revealed how the subtle twisting and stiffening of aromatic protein residues' spatial arrangement as well as the confinement of small water clusters between ligand and protein cavity due to the ligand binding can be examined using Kerr spectroscopy. Comparison between the signals of bound complex and that of uncorrelated protein/ligand demonstrated that binding action alone has reflection in the OKE spectrum. Our study indicated OKE as a powerful terahertz probe for protein-ligand binding chemistry and dynamics.

6.
Acta Pharmacol Sin ; 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34737420

RESUMO

Gefitinib has been available in the market for 20 years, but its pharmacokinetic mechanism of response is little known. In this study, we examined the pharmacokinetic and metabolomic profiles in non-small cell lung cancer (NSCLC) patients with sensitive EGFR mutations. A total of 216 advanced NSCLC patients were enrolled, and administered gefitinib at the standard dosage of 250 mg/day, which was established in heterogeneous subjects with non-sensitive mutations. We identified and quantified three main metabolites (named as M1, M2 and M3) in the plasma of patients, the correlations between the concentration of gefitinib/metabolites and efficacy were analyzed. In exploratory and validation set, gefitinib concentration was not correlated with clinical effects. Considering the result that the therapeutic effects of 250 mg/2-day was better than that of 250 mg/day in a multiple center clinical trial, the standard dose might be higher than that for maximal efficacy according to the hypothetical dose-response curve. Among the three metabolites, the IC50 of M2 in HCC827 and PC9 cell lines was significantly lower, and Conc.brain/Conc.plasma of M2 in mice was significantly higher than those of gefitinib, suggesting its higher potential to penetrate blood-brain barrier and might be more effective in the treatment of brain metastatic tumor than gefitinib. Consistently and attractively, higher M2 plasma concentration was found to be correlated with better clinical outcome in patients with brain metastases (the median PFS of CM2 < 12 ng/mL and CM2 ≥ 12 ng/mL were 17.0 and 27.1 months, respectively, P = 0.038). The plasma concentration of M2 ≥ 12 ng/mL was a strong predictor of the PFS of NSCLC patients. In conclusion, for NSCLC patients with EGFR sensitive mutations, the standard dose is suspectable and could be decreased reasonably. M2 plays an important role in efficacy and may be more effective in the treatment of metastatic tumor than gefitinib.

7.
Front Pharmacol ; 12: 751107, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616303

RESUMO

Background: Warfarin is a commonly used oral anticoagulant. It has a narrow therapeutic window and wide variation in individualized dosing, and is used clinically for the treatment of thromboembolic diseases. Due to the widespread use of traditional Chinese medicine (TCM) in China and the complex composition and diverse mechanisms of action of TCM, the combination of TCM and warfarin in patients has led to fluctuations in the international normalized ratio of warfarin or bleeding. To ensure rational clinical use, we summarize the TCMs with which warfarin interacts and the possible mechanisms, with a view to providing a clinical reference. Aim of the study: To summarize the mechanisms by which Chinese herbal medicines affect the enhancement or weakening of the anticoagulant effect of warfarin, to provide theoretical references for clinicians and pharmacists to use warfarin safely and rationally, and to avoid the adverse effects associated with the combination of Chinese herbal medicines and warfarin. Methods: A computerized literature search of electronic databases, including PubMed, MEDLINE, Cochrane Library, Web of Science (WOS), China National Knowledge Infrastructure (CNKI) and WANFANG Data was performed. Key words used in the literature search were "warfarin", "Chinese medicine", "traditional Chinese medicine", "Chinese patent medicine" etc. and their combinations in a time limit from January 1, 1990 to May 1, 2021. A total of 64 articles were obtained following the selection process, including clinical reports, pharmacological experiments and in vitro experiments which were reviewed to determine the mechanism of the anticoagulant effect of herbal medicine on warfarin. Results: The mechanisms affecting the anticoagulant effect of warfarin are complex, and herbal medicines may enhance and diminish the anticoagulant effect of warfarin through a variety of mechanisms; thus, clinical use needs to be cautious. Some herbal medicines have shown inconsistent results in both in vivo and ex vivo experiments, pharmacology and clinical studies, and should be the focus of future research. Conclusion: With the widespread use of TCM, the combination of warfarin and TCM is more common. This article will promote clinicians' knowledge and understanding of the TCMs which interact with warfarin, in order to avoid the occurrence of adverse clinical treatment processes, and improve the efficacy and safety.

8.
Cell Commun Signal ; 19(1): 103, 2021 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-34635097

RESUMO

BACKGROUND: Transcription factor CREB is involved in the development of pulmonary hypertension (PH). However, little is known about the role and regulatory signaling of CREB in PH. METHODS: A series of techniques, including bioinformatics methods, western blot, cell proliferation and luciferase reporter assay were used to perform a comprehensive analysis of the role and regulation of CREB in proliferation of pulmonary artery smooth muscle cells (PASMCs) in PH. RESULTS: Using bioinformatic analysis of the differentially expressed genes (DEGs) identified in the development of monocrotaline (MCT)- and hypoxia-induced PH, we found the overrepresentation of CRE-containing DEGs. Western blot analysis revealed a sustained increase in total- and phosphorylated-CREB in PASMCs isolated from rats treated with MCT. Similarly, an enhanced and prolonged serum-induced CREB phosphorylation was observed in hypoxia-pretreated PASMCs. The sustained CREB phosphorylation in PASMCs may be associated with multiple protein kinases phosphorylated CREB. Additionally, hierarchical clustering analysis showed reduced expression of the majority of CREB phosphatases in PH, including regulatory subunits of PP2A, Ppp2r2c and Ppp2r3a. Cell proliferation analysis showed increased PASMCs proliferation in MCT-induced PH, an effect relied on CREB-mediated transcriptional activity. Further analysis revealed the raised intracellular labile zinc possibly from ZIP12 was associated with reduced phosphatases, increased CREB-mediated transcriptional activity and PASMCs proliferation. CONCLUSIONS: CREB pathway was overactivated in the development of PH and contributed to PASMCs proliferation, which was associated with multiple protein kinases and/or reduced CREB phosphatases and raised intracellular zinc. Thus, this study may provide a novel insight into the CREB pathway in the pathogenesis of PH. Video abstract.

9.
Front Microbiol ; 12: 698385, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34675891

RESUMO

Plant roots in soil host a repertoire of bacteria and fungi, whose ecological interactions could improve their functions and plant performance. However, the potential microbial interactions and underlying mechanisms remain largely unknown across the soil-mangrove root interface. We herein analyzed microbial intra- and inter-domain network topologies, keystone taxa, and interaction-related genes across four compartments (non-rhizosphere, rhizosphere, episphere, and endosphere) from a soil-mangrove root continuum, using amplicon and metagenome sequencing technologies. We found that both intra- and inter-domain networks displayed notable differences in the structure and topology across four compartments. Compared to three peripheral compartments, the endosphere was a distinctive compartment harboring more dense co-occurrences with a higher average connectivity in bacterial-fungal network (2.986) than in bacterial (2.628) or fungal network (2.419), which could be related to three bacterial keystone taxa (Vibrio, Anaerolineae, and Desulfarculaceae) detected in the endosphere as they are known to intensify inter-domain associations with fungi and stimulate biofilm formation. In support of this finding, we also found that the genes involved in cell-cell communications by quorum sensing (rhlI, lasI, pqsH, and lasR) and aerobic cobamide biosynthesis (cobG, cobF, and cobA) were highly enriched in the endosphere, whereas anaerobic cobamide biosynthesis (encoded by cbiT and cbiE) was dominant in three peripheral compartments. Our results provide genetic evidence for the intensified bacterial-fungal associations of root endophytes, highlighting the critical role of the soil-root interface in structuring the microbial inter-domain associations.

10.
Microbiome ; 9(1): 212, 2021 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-34702367

RESUMO

BACKGROUND: Nitrogen-fixing prokaryotes (diazotrophs) contribute substantially to nitrogen input in mangrove sediments, and their structure and nitrogen fixation rate (NFR) are significantly controlled by environmental conditions. Despite the well-known studies on diazotrophs in surficial sediments, the diversity, structure, and ecological functions of diazotrophic communities along environmental gradients of mangrove sediment across different depths are largely unknown. Here, we investigated how biological nitrogen fixation varied with the depth of mangrove sediments from the perspectives of both NFR and diazotrophic communities. RESULTS: Through acetylene reduction assay, nifH gene amplicon and metagenomic sequencing, we found that the NFR increased but the diversity of diazotrophic communities decreased with the depth of mangrove sediments. The structure of diazotrophic communities at different depths was largely driven by salinity and exhibited a clear divergence at the partitioning depth of 50 cm. Among diazotrophic genera correlated with NFR, Agrobacterium and Azotobacter were specifically enriched at 50-100 cm sediments, while Anaeromyxobacter, Rubrivivax, Methylocystis, Dickeya, and Methylomonas were more abundant at 0-50 cm. Consistent with the higher NFR, metagenomic analysis demonstrated the elevated abundance of nitrogen fixation genes (nifH/D/K) in deep sediments, where nitrification genes (amoA/B/C) and denitrification genes (nirK and norB) became less abundant. Three metagenome-assembled genomes (MAGs) of diazotrophs from deep mangrove sediments indicated their facultatively anaerobic and mixotrophic lifestyles as they contained genes for low-oxygen-dependent metabolism, hydrogenotrophic respiration, carbon fixation, and pyruvate fermentation. CONCLUSIONS: This study demonstrates the depth-dependent variability of biological nitrogen fixation in terms of NFR and diazotrophic communities, which to a certain extent relieves the degree of nitrogen limitation in deep mangrove sediments. Video Abstract.

11.
J Cell Mol Med ; 25(21): 10039-10048, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34590406

RESUMO

This study aimed to investigate the anti-tumour effect of apatinib on extensive-stage small cell lung cancer (SCLC) and elucidate the associated mechanisms. NCI-H345 cells were selected as model cells because of high expression of vascular endothelial growth factor (VEGF), VEGF receptor 2 (VEGFR2) and phosphorylated-VEGFR2 (pVEGFR2). Cells were exposed to recombinant human VEGF (rhVEGF) and apatinib. Cells were then divided into eight groups, namely, control, rhVEGF, apatinib, rhVEGF+apatinib, serum-free medium (SM), SM+rhVEGF, SM+apatinib and SM+rhVEGF+apatinib. In comparison with the control group, cell proliferation in vitro in apatinib, SM, SM+apatinib and SM+rhVEGF+apatinib groups was inhibited, particularly in SM+apatinib group. The effect of apatinib on tumour growth in vivo was investigated using a mouse xenograft tumour model. In comparison with the control group, tumour sizes were reduced in apatinib-treated group on days 34 and 37. Immunohistochemical and immunofluorescence staining revealed that VEGF, pVEGFR2, PI3K, AKT, p-ERK1/2, Ki-67 and CD31 in the tumour cells of apatinib-treated group were downregulated compared with control group. Haematoxylin and eosin staining revealed that apatinib promoted the necrosis of SCLC cells in vivo. In conclusion, apatinib inhibited the growth of SCLC cells by downregulating the expression of VEGF, pVEGFR2, p-PI3K, p-AKT, p-ERK1/2, Ki-67 and CD31.

12.
Biomed Res Int ; 2021: 5557649, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34337026

RESUMO

Background: The essential roles of the tumor microenvironment (TME) have been recognized during the initiation and progression of primary lung adenocarcinoma (LUAD). The aim of the present study was to delineate the immune landscape in both primary cancer and matched lymph node metastasis from a cohort of locally advanced stage LUAD patients with distinct outcomes. Methods: Formalin-fixed, paraffin-embedded samples were collected from 36 locally advanced LUAD patients. Transcriptome data of the tumor immune microenvironment were resolved using an immune oncology panel RNA sequencing platform. Bioinformatics approaches were used to determine the differentially expressed genes (DEGs), dysregulated pathways, and immune cell fraction between patients with early recurrence (ER) and late recurrence (LR). Results: Here, we showed that in primary cancer tissues, 23 DEGs were obtained between patients with ER and LR. Functional analysis revealed that the LR in LUAD patients may be associated with enriched gene sets belonging to the antigen presentation and MHC protein complex, innate immune response, and IFN-γ signaling pathways. Next, the transcriptome data were adopted to quantify immune cell fractions, indicating that high infiltration of mast cells and neutrophils was correlated with ER. Interestingly, similar findings were observed in metastatic lymph nodes from patients suffering from ER or LR. By analyzing the shared immune features of primary cancers and lymphatic metastases, we unraveled the prognostic value and joint utility of two DEGs, CORO1A and S100A8. Conclusions: In LUAD, the enrichment in antigen presentation, MHC protein complex, and IFN-γ signaling, and low infiltration of neutrophils in primary or metastatic nodules may be indications for a favorable prognosis. Integrated with bioinformatics approaches, transcriptome data of immune-related genes from formalin-fixed, paraffin-embedded (FFPE) samples can effectively profile the landscape of the tumor immune microenvironment and help predict clinical outcomes.


Assuntos
Adenocarcinoma de Pulmão/imunologia , Adenocarcinoma de Pulmão/patologia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Metástase Linfática/patologia , Microambiente Tumoral/imunologia , Adenocarcinoma de Pulmão/genética , Adulto , Idoso , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Recidiva Local de Neoplasia/patologia , Prognóstico , Microambiente Tumoral/genética
13.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(4): 1148-1155, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34362495

RESUMO

OBJECTIVE: To investigate the types and laboratory characteristics of non-Hodgkin lymphoma(NHL) with bone marrow invasion as the first manifestation. METHODS: 81 non-Hodgkin lymphoma patients with bone marrow invasion as the first manifestation treated in our hospital from January 2010 to July 2019 were selected. The clinical features, blood routine, lactate dehydrogenase (LDH), EB virus results, bone marrow features, immunophenotyping, gene and genetic characteristics of all patients were analyzed retrospectivel. RESULTS: Among 81 patients, 73 cases(90%) were B-cell lymphoma, 5 cases(6%) were T-cell lymphoma and 3 cases(4%) were NK/T-cell lymphoma, while the mantle cell lymphoma and diffuse large B-cell lymphoma were the highest, which accounted for 21%(17 cases) and 19.7%(16 cases), and lymphoma accounted for 8.6%(7 cases). There were 44 cases(54.3%) showed B symptoms, 65 cases (80.2%) showed abnormal blood routine. The MYD88 gene was detected in 5 of 17 cases. 25 cases of patients underwent chromosome examination, the result showed that 5 cases were t(8; 14) (q24; q32), 3 cases were complex karyotype and 17 cases were normal karyotype. 23 cases(23.4%) were EB virus positive, 42 cases(51.9%) were LDH increased. The proportion of bone marrow lymphoma cells was 1%-92%. Among them, 32 cases were diagnosed as lymphoma leukemia, and 6 cases of bone marrow lymphoma cells showed mass distribution similar to extramedullary tumor cells with bone marrow metastasis. CONCLUSION: B-cell lymphoma is the predominant NHL with bone marrow invasion as the first manifestation, while mantle cell lymphoma and diffuse large B-cell lymphoma are the most common pathological types with blood routine abnormalities. Bone marrow lymphoma cells can also present clusters of bone marrow metastasis, different types of lymphoma cells can make directional diagnosis.


Assuntos
Linfoma Difuso de Grandes Células B , Linfoma de Célula do Manto , Linfoma não Hodgkin , Adulto , Medula Óssea , Humanos , Laboratórios
14.
Sci Total Environ ; 798: 149223, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34375270

RESUMO

Calcium ions (Ca2+) can trigger coagulation-flocculation process to form macro-flocculated sludge (MFS). Thus, dosing Ca2+-containing reagents into membrane bioreactors (MBRs) is considered as a promising approach to mitigate membrane biofouling. However, a mechanistic understanding of Ca2+ addition to MBR performance remains elucidated, such as physicochemical characteristics of MFS and their functionality variations. Consequently, this study was sought to understand the interplays of Ca2+ addition and MBR performance with a focus on characterizing MFS in detail. Three parallel MBRs were amended with 82, 208 and 410 mg-Ca2+/L final concentrations. Particle size analyses revealed that MFS formation was overall enhanced by the Ca2+ addition and granular sludge with diameters of up to 900 µm was formed in the 410 mg-Ca2+/L scenario. We believed that cationic bridges facilitated by elevated Ca2+ concentrations in conjunction with coagulation-flocculation were primary mechanisms of the formation of large flocs. Moreover, significant portions of soluble proteins and polysaccharides were flocculated and precipitated by Ca2+, which demonstrated a negative correlation between extracellular polymeric substances (EPS) concentrations and the formation of MFS. Furthermore, the population abundancies of Thiotrichaceae, Sphingomonadales and Hyphomicrobiaceae decreased in the sludge with Ca2+ addition resulted in profound changes of the microbial communities in the MBRs. But MBR performance, such as chemical oxygen demand removal (over 90%), showed no variation during the MBR operation. On the contrary, total nitrogen removal was inhibited in the MBRs. It was because the enlarging MFS formed diffusion barriers to prevent organic component from entering into the sludge flocs to be consumed.


Assuntos
Membranas Artificiais , Esgotos , Reatores Biológicos , Matriz Extracelular de Substâncias Poliméricas , Floculação
15.
Cell Mol Immunol ; 18(9): 2177-2187, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34363030

RESUMO

Circular RNAs (circRNAs) regulate gene expression and participate in various biological and pathological processes. However, little is known about the effects of specific circRNAs on T helper cell 17 (Th17) differentiation and related autoimmune diseases, such as multiple sclerosis (MS). Here, using transcriptome microarray analysis at different stages of experimental autoimmune encephalomyelitis (EAE), we identified the EAE progression-related circINPP4B, which showed upregulated expression in Th17 cells from mice with EAE and during Th17 differentiation in vitro. Silencing of circINPP4B inhibited Th17 differentiation and alleviated EAE, characterized by less demyelination and Th17 infiltration in the spinal cord. Mechanistically, circINPP4B served as a sponge that directly targeted miR-30a to regulate Th17 differentiation. Furthermore, circINPP4B levels were associated with the developing phases of clinical relapsing-remitting MS patients. Our results indicate that circINPP4B plays an important role in promoting Th17 differentiation and progression of EAE by targeting miR-30a, which provides a potential diagnostic and therapeutic target for Th17-mediated MS.

16.
Bioresour Technol ; 339: 125578, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34298250

RESUMO

The full utilization of carbohydrates in lignocellulosic biomass is essential for an efficient biorefining process. In this study, co-fermentation was performed for processing ethanol and succinic from sugarcane bagasse. By optimizing the co-fermentation conditions, nutrition and feeding strategies, a novel process was developed to make full utilization of the glucose and xylose in the hydrolysate of sugarcane bagasse. The achieved concentrations of succinic acid and ethanol reached to 22.1 and 22.0 g/L, respectively, and could realize the conversion of 100 g SCB raw material into 8.6 g ethanol and 8.7 g succinic acid. It is worth mentioning that the CO2 released from S. cerevisiae in co-fermentation system was recycled by A. succinogenes to synthesize succinic acid, realized CO2 emission reduction in the process of lignocellulosic biomass biorefinery. This study provided a clue for efficient biorefinery of lignocellulosic biomass and reduction greenhouse gas emissions.


Assuntos
Saccharum , Dióxido de Carbono , Celulose , Etanol , Fermentação , Glucose , Pentoses , Saccharomyces cerevisiae , Ácido Succínico , Xilose
17.
J Hazard Mater ; 418: 126392, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34329025

RESUMO

Driven approach is vital for evaluating degradation and energy efficiencies of piezocatalysis process. Thus, piezoelectric ozonation processes driven by hydraulic (HPE-O3) and ultrasonic (UPE-O3) forces were compared systematically, using BaTiO3 as piezoelectric material for ibuprofen (IBP) degradation. The synergy indexes of HPE-O3 and UPE-O3 processes were 4.51 and 5.78, respectively. Besides, UPE-O3 process (88.84%) achieved better mineralization efficiency than HPE-O3 process (68.80%) in 90 min. Nevertheless, the energy consumptions of HPE-O3 process was only 4.01‰ of UPE-O3 process. The formation rate and concentration of •OH (the dominant active species in both processes) in UPE-O3 process were 2-3 times higher than that in HPE-O3 process. Notably, piezoelectric potential and current density driven by ultrasound were approximately 47500-fold and 40-fold than those by hydro-energy, respectively. These led to the difference of •OH paths between HPE-O3 and UPE-O3 processes. Further analyses indicated that •OH was mainly generated by single-electron transfer without H2O2 generation in HPE-O3 process, whereas both single- and double-electron transfer (with H2O2 generation) contributed to the production of •OH in UPE-O3 process. This study revealed the mechanism of piezoelectric ozonation process with different driven approaches and may provide valuable reference for selection of driven approaches in piezocatalytic study and application.


Assuntos
Ozônio , Poluentes Químicos da Água , Purificação da Água , Peróxido de Hidrogênio , Ibuprofeno , Oxirredução , Poluentes Químicos da Água/análise
18.
Appl Opt ; 60(20): 5795-5804, 2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34263798

RESUMO

Temperature variations affect the accuracy of fiber-optic shape sensors; thus, temperature compensation is particularly important. This study developed a temperature self-compensation algorithm and verified the measuring accuracy of shape sensors after temperature compensation. A multicore fiber Bragg grating (FBG) sensor array was calibrated to confirm the consistency of sensor characteristics, and the relationship between the curvature and wavelength shift of FBGs was studied. A variable-temperature experiment revealed the temperature sensitivity of the FBG sensors, and these results were used by the temperature self-compensation algorithm. Further, shape reconstruction before and after temperature compensation was studied. The deformed shapes of the multicore FBG sensor array under different bending conditions were reconstructed. The results obtained after temperature compensation show that the average error between the measured and the theoretical coordinate values as less than 0.33 mm, the maximum error as less than 5.61 mm, and the relative error as less than 3.50%. The proposed temperature self-compensation algorithm has excellent prospects for application to flexible structures.

19.
Bioresour Technol ; 337: 125341, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34098499

RESUMO

Expensive cellulase is one of the major obstacles hinders large-scale biorefining of lignocellulosic biomass. The cheap and biodegradable additives sophorolipid and whey protein were found to boost enzymatic hydrolysis, their mechanisms were clarified firstly in this study. Results showed that the effects of these additives on enhancing enzymatic hydrolysis were positively correlated with substrate content; when the solid dosage was 20% (w/v), the presence of sophorolipid and whey protein increased glucose yield by 17.8% and 11.9%, respectively; this could be attributed to sophorolipid favor to alleviate the non-productive adsorption between undesired substrates and enzymes caused by hydrophobic and electrostatic forces, and the ability of whey protein to block the site of enzyme adsorption of lignin; high shear and temperature conditions accelerate the inactivation of cellulase, and the addition of sophorolipid and whey protein reduced the inactivation rate by 7.8% and 13.6%, respectively, under enzymatic hydrolysis conditions.


Assuntos
Celulase , Lignina , Biomassa , Hidrólise
20.
PLoS Biol ; 19(6): e3001281, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34077419

RESUMO

Nutrient-responsive protein kinases control the balance between anabolic growth and catabolic processes such as autophagy. Aberrant regulation of these kinases is a major cause of human disease. We report here that the vertebrate nonreceptor tyrosine kinase Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites (SRMS) inhibits autophagy and promotes growth in a nutrient-responsive manner. Under nutrient-replete conditions, SRMS phosphorylates the PHLPP scaffold FK506-binding protein 51 (FKBP51), disrupts the FKBP51-PHLPP complex, and promotes FKBP51 degradation through the ubiquitin-proteasome pathway. This prevents PHLPP-mediated dephosphorylation of AKT, causing sustained AKT activation that promotes growth and inhibits autophagy. SRMS is amplified and overexpressed in human cancers where it drives unrestrained AKT signaling in a kinase-dependent manner. SRMS kinase inhibition activates autophagy, inhibits cancer growth, and can be accomplished using the FDA-approved tyrosine kinase inhibitor ibrutinib. This illuminates SRMS as a targetable vulnerability in human cancers and as a new target for pharmacological induction of autophagy in vertebrates.


Assuntos
Autofagia , Neoplasias/metabolismo , Neoplasias/patologia , Proteínas de Ligação a Tacrolimo/metabolismo , Quinases da Família src/metabolismo , Adenina/análogos & derivados , Adenina/farmacologia , Animais , Autofagia/efeitos dos fármacos , Proteína Beclina-1/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Camundongos , Proteínas Nucleares/metabolismo , Fosfoproteínas Fosfatases/metabolismo , Fosforilação/efeitos dos fármacos , Fosfotirosina/metabolismo , Piperidinas/farmacologia , Ligação Proteica/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Quinases da Família src/antagonistas & inibidores
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