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1.
Food Chem ; 367: 130730, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34375892

RESUMO

Rhubarb has been used as herbal purgative with a worldwide long history. In traditional Chinese medicine, rhubarb can be stir-baked to scorch to eliminate the purgative function when it is a side effect. Under-scorched rhubarb still has the side effect of purgative, while over-scorched rhubarb can lose all bioactivities. Empirically, the degree of scorching is determined by manual observation of the rhubarb color. In order to find the reasonable and objective scorching endpoint criteria, visible spectrophotometry, FTIR spectroscopy and HPLC were used to reveal the color-reflected chemical changes. It was found that the blackening of rhubarb corresponded to the elimination of combined anthraquinones and the rise-fall inflection of free anthraquinones. The scorching endpoint criteria should include the upper limit for combined anthraquinones to avoid under-scorch and the lower limit for free anthraquinones to avoid over-scorch. Visible and FTIR spectroscopy can be process analytical techniques for the rhubarb scorching.


Assuntos
Medicamentos de Ervas Chinesas , Rheum , Antraquinonas , Cromatografia Líquida de Alta Pressão , Rizoma , Espectroscopia de Infravermelho com Transformada de Fourier
2.
Exp Ther Med ; 22(5): 1323, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34630677

RESUMO

Intervertebral disc degeneration (IDD) is a common disease with a high morbidity rate, which results in a significant deterioration in the quality of life of patients. MicroRNAs (miRNAs/miRs) are a class of endogenous small non-coding RNAs that influence target genes and serve critical roles in numerous biological processes. However, the role of miR-489-3p in lumbar disc degeneration is yet to be elucidated. In the present study, human NP cells were treated with 10 ng/ml lipopolysaccharide (LPS) for 24 h to investigate the role of miR-489-3p in IDD in an in vitro model. Reverse transcription-quantitative (RT-q)PCR was performed to determine the expression levels of miR-489-3p. Then, the TargetScan database was used to predict the potential binding sites between miR-489-3p and Toll-like receptor (TLR)4, and a dual-luciferase reporter assay was performed to verify the findings. Subsequently, RT-qPCR and western blotting were used to analyze the expression levels of TLR4. In addition, human nucleus pulposus (NP) cells were transfected with a miR-489-3p mimic and TLR4 overexpression plasmid to study the effects of miR-489-3p on LPS-induced human NP cells. Cell apoptosis and cell viability were also determined using flow cytometry and MTT assays, respectively. Finally, ELISAs were performed to analyze the levels of inflammatory factors. The expression levels of miR-489-3p were discovered to be downregulated in LPS-treated human NP cells. In addition, TLR4 was revealed to be a direct target gene of miR-489-3p, and its expression levels were upregulated in LPS-treated human NP cells. miR-489-3p was found to inhibit the LPS-induced decreases in cell viability and increases in apoptosis, and the concentration of inflammatory cytokines. Furthermore, miR-489-3p suppressed the LPS-induced decreases in extracellular matrix deposition via decreasing the expression levels of aggrecan and collagen type II in human NP cells. Finally, the results revealed that miR-489-3p inhibited the LPS-induced activation of the NF-κB signaling pathway in human NP cells. Conversely, all of the effects of miR-489-3p on LPS-induced human NP cells were reversed by the TLR4 overexpression plasmid. These findings suggested that miR-489-3p may represent a novel therapeutic target for the treatment of IDD.

3.
Ying Yong Sheng Tai Xue Bao ; 32(8): 2763-2772, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34664449

RESUMO

Based on data from 49 plots of natural Larix gmelinii forests in Cuigang Forest Farm of Xinlin Forestry Bureau, Daxing'anling Mountains, China, we used 37 measurable variables that mainly focused on stand non-spatial structure, stand spatial structure, species diversity, soil condition, and site condition to construct the structural equation model of natural regeneration densities and size diversities (i.e., height and ground-diameter). The direct, indirect, and total influence coefficients of each path were quantified to extract the critical and controllable factors that influence regeneration density and diversity of natural L. gmelinii forests, which would help implement sustainable forest management. The results showed that the effects of various latent variables on rege-neration density were following an order as: stand non-spatial structure (-0.410) > species diversity (0.380) > soil condition (0.250) > site condition (0.249) > stand spatial structure (0.197), while the order were changed as: soil condition (0.778) > site condition (0.748) > stand spatial structure (0.684) > stand non-spatial structure (0.287) > forest diversity (0.105), when evaluated on the regeneration diversity. Generally, the critical and controllable factors affecting rege-neration quantity and diversity were soil pH, total potassium concentration, species diversity, tree height diversity, uniform angle index and stand volume per hectare. In the management, suitable thinning treatments or replanting broadleaved trees were recommended for optimizing and adjusting species composition, species diversity, soil pH and nutrition, which would promote natural regene-ration.

5.
Food Funct ; 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34652352

RESUMO

Background. Inflammatory bowel disease (IBD) is a chronic relapsing disorder of the gastrointestinal tract. The nutrition care gut relief formula (GR), a combination of natural products and nutrients, has been shown to benefit gastrointestinal health. However, the underlying mechanism responsible for this effect is incompletely defined. Objective. This study was conducted to evaluate the hypothesis that GR could attenuate dextran sulfate sodium (DSS)-induced colitis by enhancing intestinal mucosal immunity and regulating intestinal microflora in mice. Methods. Six-week-old C57BL/6J mice orally administered with GR (7.5 mg per mouse per day) or an equal volume of vehicle were treated with sterile water or 2.5% DSS for 6 days to induce colitis. Histological damage, inflammatory cell infiltration, and colonic microbiome community were analyzed to evaluate the beneficial effect of GR. Results. GR administration ameliorated the severity of colitis as evidenced by reduced body weight loss, decreased colon shortening, reduced myeloperoxidase (MPO) activity, inhibited proinflammatory cytokine secretion, and decreased histological damage in DSS-challenged mice. Additionally, enhancement of malondialdehyde (MDA) and hydrogen peroxide (H2O2) in response to DSS was attenuated by GR administration. Meanwhile, DSS treatment resulted in reduction of the glutathione (GSH) level and tight junction protein abundance, as compared with the controls. Of note, these adverse effects were remarkably eliminated by GR administration. Further study showed that the protective effect of GR was associated with the inhibited activation of STAT3 and NF-κB signaling pathways, as well as upregulated abundances of Lactobacillus in the colon tissues of mice. Conclusion. Collectively, the data provided herein demonstrated that GR administration alleviated intestinal mucosal inflammation and mucosal barrier dysfunction. These beneficial effects were associated with inhibited activation of STAT3 and NF-κB signaling pathways, as well as upregulated abundances of Lactobacillus in the colon tissues of mice.

6.
Phys Rev Lett ; 127(9): 090501, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34506190

RESUMO

Non-Hermitian topological phases exhibit a number of exotic features that have no Hermitian counterparts, including the skin effect and breakdown of the conventional bulk-boundary correspondence. Here, we implement the non-Hermitian Su-Schrieffer-Heeger Hamiltonian, which is a prototypical model for studying non-Hermitian topological phases, with a solid-state quantum simulator consisting of an electron spin and a ^{13}C nuclear spin in a nitrogen-vacancy center in a diamond. By employing a dilation method, we realize the desired nonunitary dynamics for the electron spin and map out its spin texture in the momentum space, from which the corresponding topological invariant can be obtained directly. From the measured spin textures with varying parameters, we observe both integer and fractional winding numbers. The non-Hermitian topological phase with fractional winding number cannot be continuously deformed to any Hermitian topological phase and is intrinsic to non-Hermitian systems. Our result paves the way for further exploiting and understanding the intriguing properties of non-Hermitian topological phases with solid-state spins or other quantum simulation platforms.

7.
Int J Biol Macromol ; 190: 130-140, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34481848

RESUMO

Quinoa starch was developed as a new kind of Pickering emulsifier by enzymatic modification. The morphological structure, crystalline structure, lamellar structure, fractal structure, particle size distribution, contact angle, emulsion index (EI), and emulsion micromorphology were studied to explore the relationship between structure characteristics, hydrophilic property, and emulsifying properties of enzymatically modified (EM) quinoa starches. With the increasing enzymatic hydrolysis time in the test range of 0-9 h, particle size of EM quinoa starch decreased, and the broken starch and contact angle of EM quinoa starch increased; the EI value of emulsions with EM quinoa starch increased, and the oil droplet size of emulsions with EM quinoa starch decreased. It suggested that both the smallest particle size and the closest extent of the contact angle to 90° derived the best emulsifying property of EM-9. The EM quinoa starch had higher emulsifying capacity at higher oil volume fraction (Φ) (50%) than at lower Φ (20%), proving that the EM starch has potential to be used as Pickering emulsifiers in higher oil products, such as salad dressing.

8.
Biomedicines ; 9(9)2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34572337

RESUMO

Abnormal miRNA functions are widely involved in many diseases recorded in the database of experimentally supported human miRNA-disease associations (HMDD). Some of the associations are complicated: There can be up to five heterogeneous association types of miRNA with the same disease, including genetics type, epigenetics type, circulating miRNAs type, miRNA tissue expression type and miRNA-target interaction type. When one type of association is known for an miRNA-disease pair, it is important to predict any other types of the association for a better understanding of the disease mechanism. It is even more important to reveal associations for currently unassociated miRNAs and diseases. Methods have been recently proposed to make predictions on the association types of miRNA-disease pairs through restricted Boltzman machines, label propagation theories and tensor completion algorithms. None of them has exploited the non-linear characteristics in the miRNA-disease association network to improve the performance. We propose to use attributed multi-layer heterogeneous network embedding to learn the latent representations of miRNAs and diseases from each association type and then to predict the existence of the association type for all the miRNA-disease pairs. The performance of our method is compared with two newest methods via 10-fold cross-validation on the database HMDD v3.2 to demonstrate the superior prediction achieved by our method under different settings. Moreover, our real predictions made beyond the HMDD database can be all validated by NCBI literatures, confirming that our method is capable of accurately predicting new associations of miRNAs with diseases and their association types as well.

9.
Zhongguo Zhong Yao Za Zhi ; 46(15): 3949-3959, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34472272

RESUMO

Qishen Yiqi Dripping Pills(QSYQ) are used clinically to treat various myocardial ischemic diseases, such as angina pectoris, myocardial infarction, and heart failure; however, the molecular mechanism of QSYQ remains unclear, and the scientific connotation of traditional Chinese medicine(TCM) compatibility has not been systematically explained. The present study attempted to screen the critical pathway of QSYQ in the treatment of myocardial ischemia by network pharmacology and verify the therapeutic efficacy with the oxygen-glucose deprivation(OGD) model, in order to reveal the molecular mechanism of QSYQ based on the critical pathway. The key targets of QSYQ were determined by active ingredient identification and target prediction, and underwent pathway enrichment analysis and functional annotation with David database to reveal the biological role and the critical pathway of QSYQ. Cell counting Kit-8(CCK-8), lactate dehydrogenase(LDH), and Western blot tests were launched on high-content active ingredients with OGD cell model to reveal the molecular mechanism of QSYQ based on the critical pathway. The results of network pharmacology indicated that QSYQ, containing 18 active ingredients and 82 key targets, could protect cardiomyocytes by regulating biological functions, such as nitric oxide biosynthesis, apoptosis, inflammation, and angiogenesis, through TNF signaling pathway, HIF-1 signaling pathway, PI3 K-Akt signaling pathway, etc. HIF-1 signaling pathway was the critical pathway. As revealed by CCK-8 and LDH tests, astragaloside Ⅳ, salvianic acid A, and ginsenoside Rg_1 in QSYQ could enhance cell viability and reduce LDH in the cell supernatant in a concentration-dependent manner(P<0.05). As demonstrated by the Western blot test, astragaloside Ⅳ significantly down-regulated the protein expression of serine/threonine-protein kinase(Akt1) and hypoxia-inducible factor 1α(HIF-1α) in the HIF-1 signaling pathway, and up-regulated the protein expression of vascular endothelial growth factor A(VEGFA). Salvianic acid A significantly down-regulated the protein expression of upstream phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3 CA) and downstream HIF-1α of Akt1. Ginsenoside Rg_1 significantly down-regulated the expression of HIF-1α protein and up-regulated the expression of VEGFA. The therapeutic efficacy of QSYQ on myocardial ischemia was achieved by multiple targets and multiple pathways, with the HIF-1 signaling pathway serving as the critical one. The active ingredients of QSYQ could protect cardiomyocytes synergistically by regulating the targets in the HIF-1 signaling pathway to inhibit its expression.


Assuntos
Medicamentos de Ervas Chinesas , Isquemia Miocárdica , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Isquemia Miocárdica/tratamento farmacológico , Isquemia Miocárdica/genética , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular
10.
J Transl Med ; 19(1): 379, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488791

RESUMO

BACKGROUND: Since interferon regulatory factor (IRF) family functions in immune response to viral infection, its role in colorectal cancer (CRC) has not been inspected before. This study tries to investigate members of IRF family using bioinformatics approaches in aspect of differential expressions, biological function, tumor immune infiltration and clinical prognostic value for patients with CRC. METHODS: Transcriptome profiles data, somatic mutations and clinical information of CRC were obtained from COAD/READ dataset of The Cancer Genome Atlas (TCGA) as a training set. Gene expression data (GSE17536 and GSE39582) were downloaded from the Gene Expression Omnibus as a validating set. A random forest algorithm was used to score the risk for every case. Analyzing gene and function enrichment, constructing protein-protein interaction and noncoding RNA network, identifying hub-gene, characterizing tumor immune infiltration, evaluating differences in tumor mutational burden (TMB) and sensitivity to chemotherapeutics or immunotherapy were performed by a series of online tools and R packages. Immunohistochemical (IHC) examinations were carried out validation in tissue samples. RESULTS: Principal-component analysis (PCA) suggested that the transcript expression levels of nine members of IRF family differed between normal colorectum and CRC. The risk score constructed by IRF family not only acted as an independent factor for predicting survival in CRC patients with different biological processes, signaling pathways and TMB, but also indicated different immunotherapy response with diverse immune and stromal cells infiltration. IRF3 and IRF7 were upregulated in CRC and suggested a shorter survival time in patients with CRC. Differentially expressed members of IRF family exhibited varying degrees of immune cell infiltration. IHC analysis showed a positive association between IRF3 and IRF7 expression and tumor-infiltrating immune cells, including CD4+ T cell and CD68+ macrophages. CONCLUSIONS: On account of differential expression, IRF family members can help to predict both response to immunotherapy and clinical prognosis of patients with CRC. Our bioinformatic investigation not only gives a preliminary picture of the genetic features as well as tumor microenvironment, but it may provide a clue for further experimental exploration and verification on IRF family members in CRC.


Assuntos
Neoplasias Colorretais , Fatores Reguladores de Interferon , Biomarcadores Tumorais , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Fatores Reguladores de Interferon/genética , Prognóstico , Microambiente Tumoral
11.
Curr Med Sci ; 41(4): 803-814, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34403106

RESUMO

OBJECTIVE: Autophagy was prominently activated by cerebral ischaemia. This study was to investigate the exact role of autophagy in ischaemic stroke. METHODS: Two rat models of transient middle cerebral artery occlusion (tMCAO) and permanent MCAO (pMCAO) were prepared. The brain tissues in the penumbra were obtained to observe the dynamic variations of autophagy activity with Beclin1 and LC3 antibodies by Western blotting. At the characteristic time points, when autophagy activity was markedly elevated or reduced, the autophagy activation signaling was intervened with rapamycin and 3-methyladenine, respectively. Thereafter, key proteins in the autopahgic/lysosomal pathway were detected with the antibodies of LC3, p62, ubiquitin, LAMP-1 and cathepsin B. Meanwhile, TTC staining, neurological score and immunofluorescence were performed to evaluate brain infarct volume, neurological deficit and neuron survival, respectively. RESULTS: Both Beclin1 and LC3 expression levels were remarkably altered at 6 h, 12 h, 2 days and 7 days after tMCAO. Interestingly, the dynamic changes of autophagy activity following pMCAO were identical to those after tMCAO. Neither autophagy induction nor autophagy inhibition was able to ameliorate the pMCAO-induced neurological injury due to lysosomal dysfunction, as indicated by low levels of LAMP-1 and cathepsin B, accompanied with the accumulation of LC3-II, ubiquitin and insoluble p62. Comparatively, autophagy induction elicited overt neuroprotection at 2 and 7 days after tMCAO, and this neuroprotection might be elicited by the enhancement of autophagy flux. CONCLUSION: Our study suggests that autophagy confers neuroprotection at the subacute phase of tMCAO but has few effects on neurological outcomes after pMCAO.

12.
Microb Pathog ; 158: 105118, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34339795

RESUMO

Porcine circovirus type 2 (PCV2) can cause various clinical diseases in pigs, resulting in huge losses for the pig farms all over the world. In order to develop a new strategy to control PCV2, it is essential to understand its mechanisms firstly, especially PCV2 interferes with the host's innate immunity. In the present study, lncRNA and mRNA expression profiles in porcine lymphnode response to PCV2 infection were deeply sequenced and analyzed. 3271 novel lncRNAs were identified in all. 1898 mRNAs and 282 lncRNAs showed differential expression between control and PCV2-infected groups. The bioinformatics analysis including lncRNA-mRNA co-expression network construction, as well as GO and KEGG pathway analysis focused on the DEGs was carried out. The results indicated that lncRNAs might participate in PCV2 infection-induced the pathogenesis of immunosuppression through regulating the host's immune responses, biological regulation, response to stimulus, cellular component organization or biogenesis and metabolism. And these differentially expressed lncRNAs might play important roles in response to PCV2 infection in the host's innate immune system. These findings provided a large-scale survey of dysregulated lncRNAs after PCV2 infection, especially the lncRNAs responded to host's innate immune within the lymphnode. This study will provide a novel insight into the lncRNAs' functions and the possible immunosuppressive mechanism induced by PCV2 infection. However, further research will be required to verify the characteristic function of the dysregulated lncRNAs.


Assuntos
Infecções por Circoviridae , Circovirus , RNA Longo não Codificante , Doenças dos Suínos , Animais , Infecções por Circoviridae/veterinária , Circovirus/genética , Biologia Computacional , RNA Longo não Codificante/genética , RNA Mensageiro/genética , Suínos
13.
J Transl Med ; 19(1): 347, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34389031

RESUMO

BACKGROUND: Tumor-associated macrophages (TAM) are immunosuppressive cells that contribute to impaired anti-cancer immunity. Iron plays a critical role in regulating macrophage function. However, it is still elusive whether it can drive the functional polarization of macrophages in the context of cancer and how tumor cells affect the iron-handing properties of TAM. In this study, using hepatocellular carcinoma (HCC) as a study model, we aimed to explore the effect and mechanism of reduced ferrous iron in TAM. METHODS: TAM from HCC patients and mouse HCC tissues were collected to analyze the level of ferrous iron. Quantitative real-time PCR was used to assess M1 or M2 signature genes of macrophages treated with iron chelators. A co-culture system was established to explore the iron competition between macrophages and HCC cells. Flow cytometry analysis was performed to determine the holo-transferrin uptake of macrophages. HCC samples from The Cancer Genome Atlas (TCGA) were enrolled to evaluate the prognostic value of transferrin receptor (TFRC) and its relevance to tumor-infiltrating M2 macrophages. RESULTS: We revealed that ferrous iron in M2-like TAM is lower than that in M1-like TAM. In vitro analysis showed that loss of iron-induced immunosuppressive M2 polarization of mouse macrophages. Further experiments showed that TFRC, the primary receptor for transferrin-mediated iron uptake, was overexpressed on HCC cells but not TAM. Mechanistically, HCC cells competed with macrophages for iron to upregulate the expression of M2-related genes via induction of HIF-1α, thus contributing to M2-like TAM polarization. We further clarified the oncogenic role of TFRC in HCC patients by TCGA. TFRC is significantly increased in varieties of malignancies, including HCC, and HCC patients with high TFRC levels have considerably shortened overall survival. Also, TFRC is shown to be positively related to tumor-infiltrating M2 macrophages. CONCLUSIONS: Collectively, we identified iron starvation through TFRC-mediated iron competition drives functional immunosuppressive polarization of TAM, providing new insight into the interconnection between iron metabolism and tumor immunity.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Linhagem Celular Tumoral , Humanos , Ferro , Camundongos , Macrófagos Associados a Tumor
14.
Sensors (Basel) ; 21(16)2021 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-34450787

RESUMO

A weak C-axis preferred AlN thin film with a lot of defects was fabricated for temperature measurement. It was found that the (002) diffraction peak of the thin film increased monotonously with the increase in annealing temperature and annealing time. This phenomenon is ascribed to the evolution of defects in the lattice of the AlN film. Therefore, the relationship between defects and annealing can be expressed by the offset of (002) diffraction peak, which can be used for temperature measurement. Furthermore, a temperature interpretation algorithm Equation based on the lattice parameter (2θ), annealing temperature and annealing time was established, and a temperature interpretation software was built with MATLAB. Visual temperature interpretation is realized by the software, and the relative error is less than 7%. This study is of great significance for promoting the accurate temperature measurement on the surface of high temperature component.

15.
Chem Sci ; 12(31): 10426-10435, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34447534

RESUMO

MicroRNAs (miRNAs) play key roles in the post-transcriptional regulation of genes, and their aberrant expression may disturb the normal gene regulation network to induce various diseases, and thus accurate detection of miRNAs is essential to early clinical diagnosis. Herein, we develop for the first time a single-quantum dot (QD)-based Förster resonance energy transfer (FRET) nanosensor to accurately detect miRNAs based on copper-free and enzyme-free cycling click chemistry-mediated tricyclic ligase chain reaction (LCR) amplification. We design four DNA probes namely DNA probes 1-4, with DNA probes 1 and 3 being modified with azide (N3) and DNA probes 2 and 4 being modified with dibenzocyclooctyne (DBCO). When target miRNA is present, DNA probes 1 and 2 can proceed via copper-free and enzyme-free click chemistry to generate the probes 1-2 ligation product. Subsequently, DNA probes 3 and 4 can hybridize with the probes 1-2 ligation product to generate the probes 3-4 ligation product. Both the probes 1-2 ligation product and probes 3-4 ligation product can act as the templates to initiate cycling click chemistry-mediated tricyclic LCR amplification whose products can be easily measured by the single-QD-based FRET nanosensor. This assay does not involve any enzymatic reverse transcription, copper catalyst, and ligase enzyme, and it exhibits excellent selectivity, high sensitivity, and the capability of differentiating even single-base mismatches. Moreover, this nanosensor can accurately quantify miRNA-155 even at the single-cell level, and it can distinguish the miRNA-155 expression in tissues of healthy persons and nonsmall cell lung cancer (NSCLC) patients.

16.
Environ Toxicol ; 36(10): 2073-2092, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34251737

RESUMO

Arsenic is a well-known environmental toxicant and carcinogen, which has been epidemiologically proved related to the increased hepatic disorders. Researches have shown that aseptic inflammation and abnormal immune response are associated with arsenic-induced liver injury. However, the immunotoxic effects of liver have not been extensively characterized. Ginkgo biloba extract (GBE), a natural products of G. biloba leaves with proven anti-inflammatory and potential immunoregulatory activities, was used as intervention agent to explore its protective effects on arsenic-induced hepatotoxicity. Thus, the underlying mechanism of the immunotoxic effects on arsenic-induced liver injury were investigated in 2.5, 5.0, and 10.0 mg/kg NaAsO2 of Wistar rats for 16 weeks. Subsequently, GBE was used as intervention agent in 50 mg/kg for 6 weeks after cessation of arsenic exposure. The ratio of Th17 to Treg cells in peripheral blood as well as the secretion of inflammatory cytokines IL-17A, IL-6, TGF-ß1, and IL-10 in serum and liver were detected. Meanwhile, the notable activation of aseptic inflammation-related molecule TLR4 and its downstream targets MyD88 and NF-κB in the liver were observed. In this work, we confirmed that subchronic exposed to arsenic triggered the infiltration of inflammatory cells in rat liver, coupled with obvious histopathological changes and aberrant hepatic serum biochemical parameters. Meanwhile, imbalanced immune response was verified by the notable abnormal ratio of Th17 to Treg cells in peripheral blood as well as the secretion of inflammatory cytokines IL-17A, IL-6, TGF-ß1, and IL-10 in serum and liver of arsenic exposed rats. Further, the level of TLR4, MyD88, and NF-κB in liver both transcription and translation activity were raised. Subsequently, GBE markedly mitigated arsenic-induced liver injury, most impressively, post treatment with GBE prominently suppressed the overactivated inflammatory-related TLR4-MyD88-NF-κB pathway and evidently decreased the secretion of inflammation cytokines. Meanwhile, the disturbance of pro- and anti-inflammatory response was reversed. We concluded that the disruption of pro- and anti-inflammatory T-cells balance caused by cytokines mediated cell-cell interactions may be one of the mechanisms underlying arsenic-induced liver injury and that GBE intervention exerts an evidence protective effects, which might be closely associated with the suppression of inflammatory-related TLR4 pathway.


Assuntos
Arsênio , Doença Hepática Crônica Induzida por Substâncias e Drogas , Animais , Arsênio/toxicidade , Comunicação Celular , Citocinas , Extratos Vegetais/farmacologia , Ratos , Ratos Wistar
17.
BMC Med ; 19(1): 153, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34210292

RESUMO

BACKGROUND: Lung function is constantly changing over the life course. Although the relation of cross-sectional lung function measure and adverse outcomes has been reported, data on longitudinal change and subsequent cardiovascular (CV) events risks are scarce. Therefore, this study is to determine the association of longitudinal change in lung function and subsequent cardiovascular risks. METHODS: This study analyzed the data from four prospective cohorts. Subjects with at least two lung function tests were included. We calculated the rate of forced respiratory volume in 1 s (FEV1) and forced vital capacity (FVC) decline for each subject and categorized them into quartiles. The primary outcome was CV events, defined as a composite of coronary heart disease (CHD), chronic heart failure (CHF), stroke, and any CV death. Cox proportional hazards regression and restricted cubic spline models were applied. RESULTS: The final sample comprised 12,899 participants (mean age 48.58 years; 43.61% male). Following an average of 14.79 (10.69) years, 3950 CV events occurred. Compared with the highest FEV1 quartile (Q4), the multivariable HRs for the lowest (Q1), 2nd (Q2), and 3rd quartiles (Q3) were 1.33 (95%CI 1.19, 1.49), 1.30 (1.16, 1.46), and 1.07 (0.95, 1.21), respectively. Likewise, compared with the reference quartile (Q4), the group that experienced a faster decline in FVC had higher HRs for CV events (1.06 [95%CI 0.94-1.20] for Q3, 1.15 [1.02-1.30] for Q2, and 1.28 [1.14-1.44] for Q1). The association remained robust across a series of sensitivity analyses and nearly all subgroups but was more evident in subjects < 60 years. CONCLUSIONS: We observed a monotonic increase in risks of CV events with a faster decline in FEV1 and FVC. These findings emphasize the value of periodic evaluation of lung function and open new opportunities for disease prevention.


Assuntos
Insuficiência Cardíaca , Estudos Transversais , Feminino , Volume Expiratório Forçado , Humanos , Estudos Longitudinais , Pulmão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Capacidade Vital
18.
Phys Rev Lett ; 126(24): 240402, 2021 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-34213933

RESUMO

Non-Hermitian topological phases bear a number of exotic properties, such as the non-Hermitian skin effect and the breakdown of conventional bulk-boundary correspondence. In this Letter, we introduce an unsupervised machine learning approach to classify non-Hermitian topological phases based on diffusion maps, which are widely used in manifold learning. We find that the non-Hermitian skin effect will pose a notable obstacle, rendering the straightforward extension of unsupervised learning approaches to topological phases for Hermitian systems ineffective in clustering non-Hermitian topological phases. Through theoretical analysis and numerical simulations of two prototypical models, we show that this difficulty can be circumvented by choosing the "on-site" elements of the projective matrix as the input data. Our results provide a valuable guidance for future studies on learning non-Hermitian topological phases in an unsupervised fashion, both in theory and experiment.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34229597

RESUMO

Application of immune checkpoint inhibitors (ICIs) is a major breakthrough in the field of cancer therapy, which has displayed tremendous potential in various types of malignancies. However, their response rates range widely in different cancer types and a significant number of patients experience immune-related adverse effects (irAEs) induced by these drugs, limiting the proportion of patients who can truly benefit from ICIs. Gut microbiota has gained increasing attention due to its emerging role in regulating the immune system. In recent years, numerous studies have shown that gut microbiota can modulate antitumor response, as well as decrease the risk of colitis due to ICIs in patients receiving immunotherapy. The present review analyzed recent progress of relevant basic and clinical studies in this area and explored new perspectives to enhance the efficacy of ICIs and alleviate associated irAEs via manipulation of the gut microbiota.

20.
J Exp Clin Cancer Res ; 40(1): 221, 2021 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-34217349

RESUMO

Tumor immunity consists of various types of cells, which serve an important role in antitumor therapy. The gastrointestinal tract is colonized by trillions of microorganisms, which form the gut microbiota. In addition to pathogen defense and maintaining the intestinal ecosystem, gut microbiota also plays a pivotal role in various physiological processes. Recently, the association between these symbionts and cancer, ranging from oncogenesis and cancer progression to resistance or sensitivity to antitumor therapies, has attracted much attention. Metagenome analysis revealed a significant difference between the gut microbial composition of cancer patients and healthy individuals. Moreover, modulation of microbiome could improve therapeutic response to immune checkpoint inhibitors (ICIs). These findings suggest that microbiome is involved in cancer pathogenesis and progression through regulation of tumor immunosurveillance, although the exact mechanisms remain largely unknown. This review focuses on the interaction between the microbiome and tumor immunity, with in-depth discussion regarding the therapeutic potential of modulating gut microbiota in ICIs. Further investigations are warranted before gut microbiota can be introduced into clinical practice.

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