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1.
Cells ; 10(3)2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33807533

RESUMO

Quiescent cancer cells (QCCs) are cancer cells that are reversibly suspended in G0 phase with the ability to re-enter the cell cycle and initiate tumor growth, and, ultimately, cancer recurrence and metastasis. QCCs are also therapeutically challenging due to their resistance to most conventional cancer treatments that selectively act on proliferating cells. Considering the significant impact of QCCs on cancer progression and treatment, better understanding of appropriate experimental models, and the evaluation of QCCs are key questions in the field that have direct influence on potential pharmacological interventions. Here, this review focuses on existing and emerging preclinical models and detection methods for QCCs and discusses their respective features and scope for application. By providing a framework for selecting appropriate experimental models and investigative methods, the identification of the key players that regulate the survival and activation of QCCs and the development of more effective QCC-targeting therapeutic agents may mitigate the consequences of QCCs.

2.
Aging (Albany NY) ; 132021 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-33839698

RESUMO

Atherosclerosis (AS)-related diseases remain among the leading causes of death worldwide. Modified Xiaoyaosan (also called Tiaogan-Liqi prescription, TGLQ), a traditional Chinese medical formulation, has been widely applied in the treatment of AS-related diseases. The aim of this study was to investigate the underlying pharmacological mechanisms of TGLQ in acting on AS. A total of 548 chemical compounds contained in TGLQ, and 969 putative targets, were collected from the Computation Platform for Integrative Pharmacology of Traditional Chinese Medicine, while 1005 therapeutic targets for the treatment of AS were obtained from the DisGeNET, TTD and CTD databases. Moreover, the 63 key targets were screened by the intersection of the targets above, and by network topological analysis. Further functional enrichment analysis showed that the key targets were significantly associated with regulation of the immune system and inflammation, improvement of lipid and glucose metabolism, regulation of the neuroendocrine system and anti-thrombosis effect. The in vivo experiments confirmed that TGLQ could reduce plasma lipid profiles and plasma inflammatory cytokines, and also inhibit AS plaque formation, within the AS model ApoE-/- mice. The in vitro experiments validated the hypothesis that TGLQ could significantly reduce intracellular lipid accumulation, suppress the production of inflammatory cytokines of macrophages induced by oxidized-LDL, and inhibit the protein expression of heat shock protein 90 and toll-like receptor 4. This study identified a list of key targets of TGLQ in the treatment of AS by applying an integrative pharmacology approach, which was validated by in vivo and in vitro experimentation.

3.
J Food Sci ; 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33844282

RESUMO

Rutin (3',4',5,7-tetrahydroxy-flavone-3-rutinoside) was enzymatically acylated with benzoic acid and its esters (methyl benzoate and vinyl benzoate) using Thermomyces lanuginosus lipase (Lipozyme TLIM). The acylation reaction was optimized by varying the reaction medium, reaction temperature, acyl donor, substrate molar ratio, and reaction time. The highest conversion yield (76%) was obtained in tert-amyl alcohol (60 °C, 72 hr) using vinyl benzoate (molar ratio of 1:10) as acyl donor. The acylation occurred at the 2'''-OH and 4'''-OH of the rhamnose unit and the 2''-OH position of the glucose moieties. Three novel rutin acylated derivatives (compounds 1-3) were purified and characterized by HR-MS and 1D and 2D NMR spectroscopy. We found that acylation significantly improved lipophilicity, capacity to inhibit lipid peroxidation, anticancer capacity and substantially maintained the antioxidant activity of rutin. This research provides important insights in the acylation of flavonoids with different glycosyl moieties. PRACTICAL APPLICATION: In this study, three novel rutin derivatives were successfully synthesized and the highest conversion yield (76%) was obtained by reacting the rutin and vinyl benzoate at molar ratio of 1:10 in tert-amyl alcohol for 72 hr at 60 °C. Introducing a benzoic acid substituent into rutin molecule significantly improved their lipophilicity and inhibition of lipid peroxidation in lipophilic system. Furthermore, this study demonstrated that acylation significantly improved anticancer capacity and substantially maintained the antioxidant activity.

4.
Phytomedicine ; 85: 153522, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33799223

RESUMO

BACKGROUND: Thousands of years of clinical application of Wutou decoction (WTD) support its reliable efficacy and safety in treating rheumatoid arthritis (RA). However, the underlying molecular mechanism remains unclear, and the synergistic involvement of assistant herbs in WTD in enhancing the sovereign herb in treating RA is unknown. PURPOSE: This study aimed to investigate the efficacy-oriented compatibility of five herbs in WTD and the underlying mechanisms. METHODS: The anti-arthritic effects of WTD and the compatibilities of the five herbs in WTD were studied in vivo with adjuvant-induced arthritis (AIA) rat model and in vitro with LPS-induced RAW264.7 macrophage. Network pharmacology analysis was conducted to identify the dominant pathways involved in the anti-arthritis mechanisms of WTD and how the five herbs work synergistically. The results were further verified by in vivo and in vitro experiments. RESULTS: Our data revealed that the five herbs in WTD exert synergistic anti-arthritic effects on RA. Moreover, Radix Aconite (AC) is the principal anti-inflammatory component in WTD according to the extent of therapeutic effects exerted on the AIA rats. In vivo and in vitro experiments demonstrated that WTD inhibited NF-κB phosphorylation and simultaneously increased the expression of Nrf2, which were the major pathways identified by the network pharmacology analysis. The major assistant component, Herba Ephedrae (EP), evidently inhibited NF-κB mediated inflammatory response. The other assistant component, Radix Astragali (AS), considerably enhanced the expression of Nrf2 when used alone or in combination with AC. These combinations improved the anti-arthritis effects on the AIA rats better than that of AC alone. Nevertheless, WTD always achieved the best effects than any combinations both in vivo and in vitro. CONCLUSION: The ministerial herbs EP and AS intensify the anti-arthritic effects of AC by regulating the NF-κB-mediated inflammatory pathway and the Nrf2-mediated anti-oxidation pathway which are the major pathways of WTD for alleviating the symptoms of RA.

5.
J Med Chem ; 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33797901

RESUMO

The approvals of idelalisib and duvelisib have validated PI3Kδ inhibitors for the treatment for hematological malignancies driven by the PI3K/AKT pathway. Our program led to the identification of structurally distinct heterocycloalkyl purine inhibitors with excellent isoform and kinome selectivity; however, they had high projected human doses. Improved ligand contacts gave potency enhancements, while replacement of metabolic liabilities led to extended half-lives in preclinical species, affording PI3Kδ inhibitors with low once-daily predicted human doses. Treatment of C57BL/6-Foxp3-GDL reporter mice with 30 and 100 mg/kg/day of 3c (MSD-496486311) led to a 70% reduction in Foxp3-expressing regulatory T cells as observed through bioluminescence imaging with luciferin, consistent with the role of PI3K/AKT signaling in Treg cell proliferation. As a model for allergic rhinitis and asthma, treatment of ovalbumin-challenged Brown Norway rats with 0.3 to 30 mg/kg/day of 3c gave a dose-dependent reduction in pulmonary bronchoalveolar lavage inflammation eosinophil cell count.

6.
Pharmacol Res ; 167: 105563, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33746053

RESUMO

Macrophages are heterogeneous cells that have different physiological functions, such as chemotaxis, phagocytosis, endocytosis, and secretion of various factors. All physiological functions of macrophages are integral to homeostasis, immune defense and tissue repair. However, in several diseases, macrophages are recruited from the blood towards inflammatory sites. This process is called macrophage migration, which promotes deleterious disease progression. Macrophage migration is a key player in many inflammatory diseases, autoimmune diseases and cancers because it contributes to the accumulation of proinflammatory factors, the destruction of tissues and the development of tumors. Therefore, macrophage migration is proposed to be a potential therapeutic target. Macrophages migrate between two-dimensional (2D) and three-dimensional (3D) environments, implying that distinct migratory features and mechanisms are involved. Compared with the 2D migration of macrophages, 3D migration involves more complex variations in cellular morphology and dynamics. The structure of the extracellular matrix, a key factor, is modified in diseases that influence macrophage 3D migration. Macrophage 3D migration relates to disease pathology. Research that focuses on macrophage 3D migration is an emerging field and was reviewed in this article to indicate the molecular and cellular mechanisms of macrophage migration in 3D environments and to provide potential targets for controlling disease progression associated with this migration.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33712429

RESUMO

Carbohydrate is the most important energy source in the diet of human and animals. A large number of studies have shown that dietary carbohydrates (DCHO) are related to the bacterial community in the gut, but its relationship with the composition of intestinal fungi is still unknown. Here, we report the response of colonic fungal community to different composition of DCHO in a pig model. Three factors, ratio of (2:1, 1:1 and 1:2) amylose to amylopectin (AM/AP), level of non-starch polysaccharides (NSP, 1%, 2% and 3%) and mannan-oligosaccharide (MOS, 400, 800 and 1,200 mg/kg), were considered according to a L9 (34) orthogonal design to form nine diets with different carbohydrate composition. Sequencing based on an Illumina HiSeq 2500 platform targeting the internal transcribed spacer 1 region showed that the fungal community in the colon of the pigs responded to DCHO in the order of MOS, AM/AP and NSP. A large part of some low-abundance fungal genera correlated with the composition of DCHO, represented by Saccharomycopsis, Mrakia, Wallemia, Cantharellus, Eruotium, Solicoccozyma and Penicillium, were also associated with the concentration of glucose and fructose, as well as the activity of ß-D-Glucosidase in the colonic digesta, suggesting a role of these fungi in the degradation of DCHO in the colon of pigs. Our study provides direct evidences for the relationship between the composition of DCHO and fungal community in the colon of pigs, which is helpful to understand the function of gut microorganisms in pigs.ImportanceAlthough fungi are a large group of microorganisms besides bacteria and archaea in the gut of monogastric animals, the nutritional significance of fungi has been ignored for a long time. Our previous studies have revealed a distinct fungal community in the gut of grazing Tibetan pigs, and a close correlation between fungal species and short-chain fatty acids, the main microbial metabolites of carbohydrates in the hindgut of pigs. These groundbreaking findings indicate a potential relationship between intestinal fungi and the utilization of DCHO. However, no evidence directly proves the response of intestinal fungi to changes in DCHO. Here, we show a clear alteration of colonic fungal community in pigs triggered by different composition of DCHO simulated by varied concentrations of starch, NSP and oligosaccharides. Our results highlight the potential involvement of intestinal fungi in the utilization of nutrients in monogastric animals.

9.
J Nat Prod ; 2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33683883

RESUMO

Guttiferone F, a natural polyprenylated polycyclic acylphloroglucinol, was originally assigned as the 30-epimer of garcinol by NMR data analyses. Conversion of guttiferone F in the presence of acid afforded its cyclized form (2a), which was previously assigned as 30-epi-cambogin. However, the absolute configurations of guttiferone F and 2a have not been determined. Reinvestigation of the structures of those two compounds, using X-ray and NMR data analyses and chemical transformation, revealed that the original assignment of the C-30 absolute configuration in guttiferone F and 2a should be inverted. Guttiferone F is indeed garcinol, and 2a, which was previously identified as 30-epi-cambogin, is cambogin.

10.
Food Chem ; 354: 129454, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33765463

RESUMO

In order to reveal the color formation mechanism of blood-red edible bird's nests (EBNs) and develop a quick and specific strategy to distinguish the artificial fake one, multiple methods of UPLC-TOF/MS, UV, NMR, FT-IR and 2D IR were used to detect the chemical markers of the reddening reaction, the results showed that the reddening substances were C9H10N2O5 and C9H9NO6, which were verified as products of a phenol-keto tautomerism evolved from l-tyrosine. Moreover, natural and artificial red EBNs with varying degrees of chemical fumigation also can be successfully distinguished using the chemical markers, and the protein variation in SDS-PAGE gel could also support the distinction. This work established a systematic method of chemical identification for both natural and artificial blood-red EBNs, and provided a new identification strategy for food safety control that can promote the development of a healthier market of EBNs.

11.
Sci Rep ; 11(1): 6969, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33772055

RESUMO

Treatment of ventilated patients with gram-negative pneumonia (GNP) is often unsuccessful. We aimed to assess the efficacy and safety of nebulized amikacin (NA) as adjunctive therapy to systemic antibiotics in this patient population. PubMed, Embase, China national knowledge infrastructure, Wanfang, and the Cochrane database were searched for randomized controlled trials (RCTs) investigating the effect of NA as adjunctive therapy in ventilated adult patients with GNP. Heterogeneity was explored using subgroup analysis and sensitivity analysis. The Grading of recommendations assessment, development, and evaluation approach was used to assess the certainty of the evidence. Thirteen RCTs with 1733 adults were included. The pooled results showed NA had better microbiologic eradication (RR = 1.51, 95% CI 1.35 to 1.69, P < 0.0001) and improved clinical response (RR = 1.23; 95% CI 1.13 to 1.34; P < 0.0001) when compared with control. Meanwhile, overall mortality, pneumonia associated mortality, duration of mechanical ventilation, length of stay in ICU and change of clinical pneumonia infection scores were similar between NA and control groups. Additionally, NA did not add significant nephrotoxicity while could cause more bronchospasm. The use of NA adjunctive to systemic antibiotics therapy showed better benefits in ventilated patients with GNP. More well-designed RCTs are still needed to confirm our results.

12.
Zhongguo Zhong Yao Za Zhi ; 46(2): 306-311, 2021 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-33645116

RESUMO

Liver is the main place of drug metabolism. Mitochondria of hepatocytes are important targets of drug-induced liver injury. Mitochondrial autophagy could maintain the healthy operation of mitochondria in cells and the stable proliferation of cells. Therefore, the use of mitochondrial autophagy to remove damaged mitochondria is an important strategy of anti-drug-induced liver injury. Active ingredients that could enhance mitochondrial autophagy are contained in many traditional Chinese medicines, which could regulate the mitochondrial autophagy to alleviate relevant diseases. However, there are only a few reports on how to accurately and efficiently identify and evaluate such components targeting mitochondria from traditional Chinese medicine. Liquid chromatography-mass spectro-metry(LC-MS) combined with serum pharmacology in vivo can be used to accurately and efficiently find active ingredients of traditional Chinese medicine acting on mitochondrial targets. This paper reviewed the research ideas and methods of traditional Chinese medicine ingredients for increasing the hepatotoxicity of mitochondrial autophagy, in order to provide new ideas and methods for the study of active ingredients of traditional Chinese medicine targeting mitochondria.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/toxicidade , Humanos , Medicina Tradicional Chinesa , Mitocôndrias
13.
Sci Adv ; 7(10)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33674310

RESUMO

Recent discovery of superconductivity in Nd0.8Sr0.2NiO2 motivates the synthesis of other nickelates for providing insights into the origin of high-temperature superconductivity. However, the synthesis of stoichiometric R 1-x Sr x NiO3 thin films over a range of x has proven challenging. Moreover, little is known about the structures and properties of the end member SrNiO3 Here, we show that spontaneous phase segregation occurs while depositing SrNiO3 thin films on perovskite oxide substrates by molecular beam epitaxy. Two coexisting oxygen-deficient Ruddlesden-Popper phases, Sr2NiO3 and SrNi2O3, are formed to balance the stoichiometry and stabilize the energetically preferred Ni2+ cation. Our study sheds light on an unusual oxide thin-film nucleation process driven by the instability in perovskite structured SrNiO3 and the tendency of transition metal cations to form their most stable valence (i.e., Ni2+ in this case). The resulting metastable reduced Ruddlesden-Popper structures offer a testbed for further studying emerging phenomena in nickel-based oxides.

14.
PLoS One ; 16(3): e0247817, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33661995

RESUMO

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is a pancreatic disease with a high mortality rate in the world. This present research intends to identify the function of lncRNA LINC00857/miR-340-5p/Transforming growth factor alpha (TGFA) in the progression of PAAD. METHODS: Bioinformatics analysis was used to explore the differentially expressed lncRNA/miRNA/mRNA and analyze the relationship between lncRNA/miRNA/mRNA expression and prognosis of PAAD by enquiring TCGA, GEO and GTEX. KEGG pathway analysis and GO enrichment analysis were implemented to annotate the crucial genes regulated by LINC00857. The biological behaviors of PAAD cells were detected by CCK-8, colony formation and transwell assays. Interactive associations between LINC00857 and miR-340-5p, as well as miR-340-5p and TGFA were analyzed by dual luciferase assay. RESULTS: By enquiring TCGA database, we got that LINC00857 was highly expressed in patients with PAAD and positively associated with worse prognosis in PAAD patients. Moreover, LINC00857 upregulation promoted the proliferation and clone formation abilities of PAAD cells. Afterwards, the downstream miRNA and mRNA targets of LINC00857 were picked up to construct a ceRNA network. Further study revealed that TGFA expression was positively regulated by LINC00857 and negatively regulated by miR-340-5p. Besides that, the inhibitory effect of miR-340-5p on PAAD cells growth and movement can be blocked by LINC00857 upregulation. While, the malignant behavior of PAAD cells induced by TGFA overexpression can be eliminated by LINC00857 knockdown. CONCLUSIONS: Upregulation of LINC00857 improved growth, invasion and migration abilities of PAAD cells by modulation of miR-340-5p/TGFA, affording potential targets and biomarkers for the clinical diagnosis and treatment.

15.
Angew Chem Int Ed Engl ; 60(16): 8976-8982, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33555646

RESUMO

Oxidative cleavage of C(OH)-C bonds to afford carboxylates is of significant importance for the petrochemical industry and biomass valorization. Here we report an efficient electrochemical strategy for the selective upgrading of lignin derivatives to carboxylates by a manganese-doped cobalt oxyhydroxide (MnCoOOH) catalyst. A wide range of lignin-derived substrates with C(OH)-C or C(O)-C units undergo efficient cleavage to corresponding carboxylates in excellent yields (80-99 %) and operational stability (200 h). Detailed investigations reveal a tandem oxidation mechanism that base from the electrolyte converts secondary alcohols and their derived ketones to reactive nucleophiles, which are oxidized by electrophilic oxygen species on MnCoOOH from water. As proof of concept, this approach was applied to upgrade lignin derivatives with C(OH)-C or C(O)-C motifs, achieving convergent transformation of lignin-derived mixtures to benzoate and KA oil to adipate with 91.5 % and 64.2 % yields, respectively.

16.
Pharmacol Res ; : 105519, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33636352

RESUMO

Chinese materia medica (CMM) is indispensable component of Traditional Chinese Medicine (TCM) therapy. With the widespread of TCM around the world, the quality control and safe use of CMM become a major concern. This paper introduces the role of ISO standards for industrial development and current development status of CMM standards in ISO/TC 249. Through the comparison of similarities and differences between CMM standards in ISO/TC 249 and pharmacopoeias of main stakeholders, this paper suggests strengthening standard formulation in the following areas to provide more appropriate documents to facilitate the international trade and promote the industrial development of CMM: (1) Develop standards to fill the blanks among the whole industry chain of CMM; (2) Develop standards for new forms of CMM and services; (3) Develop specification and grade standards for CMM with large quantity and high value.

17.
Adv Mater ; 33(11): e2007829, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33554414

RESUMO

Hydrogels, exhibiting wide applications in soft robotics, tissue engineering, implantable electronics, etc., often require sophisticately tailoring of the hydrogel mechanical properties to meet specific demands. For examples, soft robotics necessitates tough hydrogels; stem cell culturing demands various tissue-matching modulus; and neuron probes desire dynamically tunable modulus. Herein, a strategy to broadly alter the mechanical properties of hydrogels reversibly via tuning the aggregation states of the polymer chains by ions based on the Hofmeister effect is reported. An ultratough poly(vinyl alcohol) (PVA) hydrogel as an exemplary material (toughness 150 ± 20 MJ m-3 ), which surpasses synthetic polymers like poly(dimethylsiloxane), synthetic rubber, and natural spider silk is fabricated. With various ions, the hydrogel's various mechanical properties are continuously and reversibly in situ modulated over a large window: tensile strength from 50 ± 9 kPa to 15 ± 1 MPa, toughness from 0.0167 ± 0.003 to 150 ± 20 MJ m-3 , elongation from 300 ± 100% to 2100 ± 300%, and modulus from 24 ± 2 to 2500 ± 140 kPa. Importantly, the ions serve as gelation triggers and property modulators only, not necessarily required to remain in the gel, maintaining the high biocompatibility of PVA without excess ions. This strategy, enabling high mechanical performance and broad dynamic tunability, presents a universal platform for broad applications from biomedicine to wearable electronics.

18.
Pharmacol Res ; : 105513, 2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33617975

RESUMO

A large number of macrophages in inflamed sites not only amplify the severity of inflammatory responses but also contribute to the deleterious progression of many chronic inflammatory diseases, autoimmune diseases and cancers. Macrophage migration is a prerequisite for their entry into inflammatory sites and their participation of macrophages in the pathologic processes. Inhibition of macrophage migration is therefore a potential anti-inflammatory mechanism. Moreover, alleviation of inflammation also prevents the macrophages infiltration. Sinomenine (SIN) is an alkaloid derived from the Chinese medicinal plant Sinomenium acutum. It has multiple pharmacological effects, including anti-inflammation, immunosuppression, and anti-arthritis. However, its anti-inflammatory molecular mechanisms and effect on macrophage migration are not fully understood. The purpose of this research was to investigate the pharmacological effects and the molecular mechanism of SIN on macrophage migration in vivo and in vitro as well as to elucidate its anti-inflammatory mechanisms associated with macrophage migration. Our results showed that SIN reduced the number of RAW264.7 cells migrating into inflammatory paws and blocked lipopolysaccharide (LPS)-induced RAW264.7 cells and bone marrow-derived macrophages (BMDMs) migration in vitro. Furthermore, SIN attenuated the 3D mesenchymal migration of BMDMs. The absence of macrophage migration after circulatory and periphery macrophages depletion led to a reduction in the severity of inflammatory response. In macrophages depleted (macrophages-/-) mice, as inflammatory severity decreased, RAW264.7 cells migration was suppressed. A non-obvious effect of SIN on the inflammatory response was found in macrophages-/- mice, while the inhibitory effect of SIN on RAW264.7 cells migration was still observed. Furthermore, the migration of RAW264.7 cells pre-treated with SIN was suppressed in normal mice. Finally, Src/focal adhesion kinase (FAK)/P130Cas axis activation, which supports macrophages mesenchymal migration, and iNOS expression, NO production, integrin αV and in integrin ß3 expressions, which promote Src/FAK/P130Cas activation, were down-regulated by SIN. However, SIN had no obvious effect on the expression of the monocyte chemoattractant protein-1 (MCP-1), which is an important chemokine for macrophage migration. These results indicated that SIN significantly inhibited macrophage mesenchymal migration by down-regulating on Src/FAK/P130Cas axis activation. There was a mutual regulatory correlation between the inflammatory response and macrophage migration, and the effects of SIN on macrophage migration were involved in its anti-inflammatory activity.

19.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(1): 1-8, 2021 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-33554789

RESUMO

OBJECTIVE: To investigate the correlation of receptor gene (P2X7, VDR and SLC19A1) polymorphisms with risk suffering from acute leukemia (AL) in Fujian area. METHODS: Ninety-three cases of newly diagnosed AL as AL group and 90 persons not suffered from hematologic and other tumors as control group were selected and used for comparative analysis of receptor gene polymorphisms and risk suffering from AL between case and control groups. The bone marrow and peripheral blood were collected, from which the DNA was extracted. The PCR-RFLP was used to detect 8 SNP sites (P2X7: rs208294, rs2230911, rs3751143; VDR: rs2228570, rs7975232; SLC194A1: rs1051266, rs1131596, rs3788200) of receptor genes related with the environment response, and the genotypes analysis was used to the correlation of receptor gene polymorphisms with risk suffering from adult AL. RESULTS: The unvariate logistic analysis showed that as compared with control group, P2X7 rs208294 T>C mutation and rs3751143 A>C mutation in codominant model, dominant model and over-dominant model were higher in case group, moreover the differences were statistically significant (P<0.01, P<0.05 and P<0.05, respectively), which suggested that they could reduce the risk suffering from AL. The recessive inheritance model showed that SLC1941 rs1131596 G>A mutation could increase the risk suffering from AL (P<0.05). The stepwise multivariate logistic regression analysis showed that there was still statistically significant difference in P2X7 rs208294 mutation between case group and control group (P<0.05), moreover, the heterozygous mutation (CT) could decrease the risk suffering from AL, showing the better protective effect, compared with homozygous mutation(CC). CONCLUSION: The P2X7 rs208294 T>C mutation is one of protective factors against adult acute leukemia.


Assuntos
Predisposição Genética para Doença , Leucemia Mieloide Aguda , Adulto , Estudos de Casos e Controles , Frequência do Gene , Genótipo , Homozigoto , Humanos , Polimorfismo Genético , Polimorfismo de Nucleotídeo Único , Receptores Purinérgicos P2X7
20.
Microbiol Immunol ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33629787

RESUMO

Due to the increased number of patients who suffer from asthma, the mechanism of this disease has caught much attention to public and to find a cure for this disease is urgent. Changed abundance of microbiome has been proven to play an important role in the genesis and development of asthma. In this study, the abundance and the function of microbiome are studied. We found that there are significant changes in the component and the function of microbiome when the asthma was changed from mild to severe. This study would help us to better understand the relationship between asthma and the respiratory microbiome. This article is protected by copyright. All rights reserved.

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