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1.
J Med Chem ; 64(8): 5049-5066, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33844532

RESUMO

Bispecific degraders (PROTACs) of ERα are expected to be advantageous over current inhibitors of ERα signaling (aromatase inhibitors/SERMs/SERDs) used to treat ER+ breast cancer. Information from DNA-encoded chemical library (DECL) screening provides a method to identify novel PROTAC binding features as the linker positioning, and binding elements are determined directly from the screen. After screening ∼120 billion DNA-encoded molecules with ERα WT and 3 gain-of-function (GOF) mutants, with and without estradiol to identify features that enrich ERα competitively, the off-DNA synthesized small molecule exemplar 7 exhibited nanomolar ERα binding, antagonism, and degradation. Click chemistry synthesis on an alkyne E3 ligase engagers panel and an azide variant of 7 rapidly generated bispecific nanomolar degraders of ERα, with PROTACs 18 and 21 inhibiting ER+ MCF7 tumor growth in a mouse xenograft model of breast cancer. This study validates this approach toward identifying novel bispecific degrader leads from DECL screening with minimal optimization.

2.
Stem Cell Res Ther ; 12(1): 232, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33845903

RESUMO

BACKGROUND: Asymmetrical cell division (ACD) maintains the proper number of stem cells to ensure self-renewal. The rate of symmetric division increases as more cancer stem cells (CSCs) become malignant; however, the signaling pathway network involved in CSC division remains elusive. FXR (Farnesoid X receptor), a ligand-activated transcription factor, has several anti-tumor effects and has been shown to target CSCs. Here, we aimed at evaluating the role of FXR in the regulation of the cell division of CSCs. METHODS: The FXR target gene and downstream molecular mechanisms were confirmed by qRT-PCR, Western blot, luciferase reporter assay, EMAS, Chip, and IF analyses. Pulse-chase BrdU labeling and paired-cell experiments were used to detect the cell division of liver CSCs. Gain- and loss-of-function experiments in Huh7 cells and mouse models were performed to support findings and elucidate the function and underlying mechanisms of FXR-Notch1 in liver CSC division. RESULTS: We demonstrated that activation of Notch1 was significantly elevated in the livers of hepatocellular carcinoma (HCC) in Farnesoid X receptor-knockout (FXR-KO) mice and that FXR expression negatively correlated with Notch1 level during chronic liver injury. Activation of FXR induced the asymmetric divisions of Sox9+ liver CSCs and ameliorated liver injury. Mechanistically, FXR directs Sox9+ liver CSCs from symmetry to asymmetry via inhibition of Notch1 expression and activity. Deletion of FXR signaling or over-expression of Notch1 greatly increased Notch1 expression and activity along with ACD reduction. FXR inhibited Notch1 expression by directly binding to its promoter FXRE. FXR also positively regulated Numb expression, contributing to a feedback circuit, which decreased Notch1 activity and directed ACD. CONCLUSION: Our findings suggest that FXR represses Notch1 expression and directs ACD of Sox9+ cells to prevent the development of liver cancer.

3.
Front Immunol ; 12: 641188, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33828552

RESUMO

Precisely controlled lymphocyte migration is critically required for immune surveillance and successful immune responses. Lymphocyte migration is strictly regulated by chemokines and chemokine receptors. Here we show that protein geranylgeranylation, a form of post-translational protein lipid modification, is required for chemokine receptor-proximal signaling. Mature thymocytes deficient for protein geranylgeranylation are impaired for thymus egress. Circulating mature T cells lacking protein geranylgeranylation fail to home to secondary lymphoid organs or to transmigrate in response to chemokines in vitro. Mechanistically, protein geranylgeranylation modifies the γ-subunits of the heterotrimeric small GTPases that are essential for chemokine receptor signaling. In addition, protein geranylgeranylation also promotes the differentiation of IL-17-producing T helper cells while inhibiting the differentiation of Foxp3+ regulatory T cells. Finally, mice with T cell lineage-specific deficiency of protein geranylgeranylation are resistant to experimental autoimmune encephalomyelitis induction. This study elucidated a critical role of protein geranylgeranylation in regulating T lymphocyte migration and function.

4.
Front Endocrinol (Lausanne) ; 12: 633856, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33692759

RESUMO

Aims: To investigate the predictive value of baseline serum triglyceride (TG) levels for improvements of metabolism after laparoscopic sleeve gastrectomy (LSG). Methods: 112 obese patients [body mass index (BMI) ≥ 35 kg/m2] underwent LSG and with complete information of anthropometric and metabolic parameters were divided into normal TG group (group A) and high TG group (group B), while group A had TG levels ≤ 1.7 mmol/L, and group B had TG levels > 1.7 mmol/L. The post-operative changes (Δ) in metabolic parameters between the two groups were compared. Results: In the whole cohort, the metabolic parameters were significantly improved at 6 months after LSG. BMI and waist circumference (WC) decreased significantly in the two groups. The ΔBMI among group A and group B were 11.42±3.23 vs 9.13±2.77 kg/m2 (p<0.001), respectively. ΔBMI was positively correlated with ΔWC (r=0.696, p<0.001), Δfasting insulin level (r=0.440, p=0.002), Δfasting serum C peptide level (r=0.453, p=0.002), and Δhomeostasis model assessment insulin resistance index (r=0.418, p=0.004) in group A. Compared with group B, group A had a significantly higher odds ratio (OR) of 2.83 (95% confidence interval [CI]1.25-6.38, p=0.012)and 2.73 (95% CI 1.11-6.72, p=0.029) for ΔBMI and ΔWC after adjustment for age and gender, respectively. Conclusions: Obese patients with baseline TG levels under 1.7 mmol/L had greater loss of weight at six months follow-up later LSG. This finding suggests that baseline TG level may have a predictive value for weight loss, at least in the short-term follow-up.

5.
Water Res ; 196: 117014, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33751971

RESUMO

Freshwater lakes are threatened by harmful cyanobacterial blooms, whose basic unit is Cyanobacterial Aggregate (CA). CA-attached bacteria play a significant role through different blooming stages with substantial variation of their taxonomic structure. However, little is known about their functional variations and functional links with cyanobacteria due to the lack of reference genomes. In this longitudinal study, we collected 16 CA samples from Lake Taihu, one of China's largest freshwater lakes, from April 2015 to February 2016, and sequenced their V4 region of 16S rRNA genes, full metagenomes (MG), and metatranscriptomes (MT). The analysis of these data revealed the dynamics of microbial taxonomic and functional structure in CAs, influenced by both external environmental factors and internal metabolism. 55 OTUs, 456 genes, and 37 transcripts showed significantly differential abundance across the early, middle, and late blooming stages (ANOVA test, P < 0.05). Total nitrogen and total phosphorus were proved to be the most important environmental drivers of microbial taxonomic and functional variations in CAs (Mantel's r > 0.25, P < 0.05). We constructed 161 high-quality metagenome-assembled genomes (MAGs), out of which 22 were cyanobacterial strains with diverse energy pathways, transporters and prokaryotic defense systems. Based on these MAGs, we constructed a cyanobacteria-bacteria co-nitrogen-pathway and a cyanobacteria-bacteria co-phosphorus-pathway, by which we demonstrated how nitrogen and phosphorus influence the dynamics of the microbial structure to a certain extent by affecting these co-pathways. Overall, these results characterized the taxonomic, functional, and transcriptional variations of microbes in CAs through different blooming stages. Genome assembly and metabolic analysis of cyanobacteria and their attached bacteria suggested that the material exchange and signal transduction do, indeed, exist among them. Our understanding of the underlying molecular pathways for cyanobacterial blooms could lead to the control of blooms by interventional strategies to disrupt critical microbes' expression.


Assuntos
Cianobactérias , Microbiota , China , Cianobactérias/genética , Eutrofização , Proliferação Nociva de Algas , Lagos , Estudos Longitudinais , RNA Ribossômico 16S/genética
6.
Sci Total Environ ; 773: 145421, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33582356

RESUMO

Harmful cyanobacterial blooms are a widespread destruction to the processes and function of aquatic ecosystems. To study effects of cyanobacterial blooms on plankton diversity and composition, we analyzed data of cyanobacterial, eukaryotic phytoplankton, metazoan zooplankton, and physicochemical samples collected from 24 sites for four seasons in 2017 and 2018 from the large, shallow Lake Taihu. We found that cyanobacterial abundance significantly correlated with phytoplankton biomass, species richness, functional richness and evenness, and zooplankton biomass, Shannon's diversity, Simpson's evenness, and functional evenness and richness. High cyanobacterial abundance during summer did not result in low species and functional diversities for both phytoplankton and zooplankton compared with other seasons. Species and functional diversities of sites with high cyanobacteria abundance were not significantly lower than other sites with relatively low cyanobacteria abundance. Structure equation modeling indicated that cyanobacteria had direct influence on phytoplankton and zooplankton compositions. Physicochemical and temporal-spatial factors had direct influence on phytoplankton and zooplankton, and had indirect influence on phytoplankton and zooplankton through direct influence on cyanobacteria. Variance partitioning analysis quantified that cyanobacteria alone and interactions with physicochemical and spatial-temporal factors explained about 10% of phytoplankton variation and 26% of zooplankton variation. Our results indicate that cyanobacteria have substantial effects on phytoplankton and zooplankton biodiversity and community composition. Physicochemical and spatial-temporal factors could potentially obscure the detection of cyanobacterial effects on plankton in Lake Taihu that has cyanobacterial blooms in all seasons. Our findings may improve the understanding of dynamics and responses of plankton communities to environmental changes and cyanobacterial bloom disturbance and enhance the capability of assessing the effectiveness of eutrophication management and restoration of aquatic ecosystems.


Assuntos
Cianobactérias , Fitoplâncton , Animais , Biomassa , China , Ecossistema , Eucariotos , Eutrofização , Lagos , Zooplâncton
7.
Public Health ; 192: 37-44, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33611170

RESUMO

OBJECTIVES: This study evaluated the characteristics of individuals with voluntary behavioural changes (cancellation and postponement of bookings) during the early stages of the coronavirus disease 2019 (COVID-19) outbreak in Japan. In addition, the temporal trends of these changes were captured. STUDY DESIGN: A cross-sectional analysis and a time series analysis were conducted. METHODS: A nation-wide retrospective panel survey was conducted at the end of March 2020 (n = 1052). Odds ratios for cancellations/postponements with respect to individual characteristics were calculated in the analysis. To determine the temporal trend, the incidence ratios were compared throughout the time series analysis for four time periods: period 1, before the announcement of the Public Health Emergency of International Concern (PHEIC) from the World Health Organisation (WHO) (January 1-31); period 2, after the announcement of PHEIC (February 1-26); period 3, after the announcement of school closures by the Japanese government (February 27 - March 11); and period 4, after the announcement of the pandemic by the WHO (March 12-31). RESULTS: In total, 72% of respondents cancelled or postponed their bookings at least once, and about half of the changes occurred in period 3. Elderly individuals' changes in gatherings were, on average, 5.9 times (95% confidence interval [CI] 1.9-17.9) higher than those of young individuals. The incidence rate of change in gatherings during period 3 was 7.11 times (95% CI: 5.16-9.81) higher than in period 2 and 3.15 times (95% CI: 2.25-4.43) higher than in period 4. Significant interaction terms were observed in age and residential city size, but not sex, of the respondents. CONCLUSIONS: A significant proportion of the Japanese population voluntarily changed their behaviour during the early stages of the COVID-19 outbreak, and the government's announcement of school closures was a key trigger during this time.


Assuntos
Ansiedade/epidemiologia , Controle de Doenças Transmissíveis/estatística & dados numéricos , Medo/psicologia , Pandemias/prevenção & controle , Adulto , Idoso , /prevenção & controle , Estudos Transversais , Surtos de Doenças , Feminino , Humanos , Incidência , Japão/epidemiologia , Masculino , Saúde Pública , Estudos Retrospectivos , Adulto Jovem
8.
J Environ Sci (China) ; 102: 159-169, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33637241

RESUMO

Nitrated polycyclic aromatic hydrocarbons (NPAHs) have toxic potentials that are higher than those of their corresponding parent polycyclic aromatic hydrocarbons (PAHs) and thus have received increasing attention in recent years. In this study, the occurrence, distribution, source, and human health risk assessment of 15 NPAHs and 16 PAHs were investigated in the surface water from 20 sampling sites of Lake Taihu during the dry, normal, and flood seasons of 2018. The ΣPAH concentrations ranged from 255 to 7298 ng/L and the ΣNPAH concentrations ranged from not-detected (ND) to 212 ng/L. Among the target analytes, 2-nitrofluorene (2-nFlu) was the predominant NPAH, with a detection frequency ranging from 85% to 90% and a maximum concentration of 56.2 ng/L. The three-ringed and four-ringed NPAHs and PAHs comprised the majority of the detected compounds. In terms of seasonal variation, the highest levels of the ΣNPAHs and ΣPAHs were in the dry season and flood season, respectively. Diagnostic ratio analysis indicated that the prime source of NPAHs was direct combustion, whereas in the case of PAHs the contribution was predominantly from a mixed pattern including pollution from unburned petroleum and petroleum combustion. The human health risk of NPAHs and PAHs was evaluated using a lifetime carcinogenic risk assessment model. The carcinogenic risk level of the targets ranged from 2.09 × 10-7 to 5.75 × 10-5 and some surface water samples posed a potential health risk.


Assuntos
Hidrocarbonetos Policíclicos Aromáticos , Poluentes Químicos da Água , China , Monitoramento Ambiental , Humanos , Lagos , Nitratos , Hidrocarbonetos Policíclicos Aromáticos/análise , Medição de Risco , Água , Poluentes Químicos da Água/análise
9.
Transp Policy (Oxf) ; 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33519127

RESUMO

Impacts of coronavirus disease 2019 (COVID-19) on the transport sector and the corresponding policy measures are becoming widely investigated. Considering the various uncertainties and unknowns about this virus and its impacts (especially long-term impacts), it is critical to understand opinions and suggestions from experts within the transport sector and related planning fields. To date, however, there is no study that fills this gap in a comprehensive way. This paper is an executive summary of the findings of the WCTRS COVID-19 Taskforce expert survey conducted worldwide between the end of April and late May 2020, obtaining 284 valid answers. The experts include those in the field of transport and other relevant disciplines, keeping good balances between geographic regions, types of workplaces, and working durations. Based on extensive analyses of the survey results, this paper first reveals the realities of lockdowns, restrictions of out-of-home activities and other physical distancing requirements, as well as modal shifts. Experts' agreements and disagreements to the structural questions about changes in lifestyles and society are then discussed. Analysis results revealed that our human society was not well prepared for the current pandemic, reaffirming the importance of risk communication. Geographical differences of modal shifts are further identified, especially related to active transport and car dependence. Improved sustainability and resilience are expected in the future but should be supported by effective behavioral intervention measures. Finally, policy implications of the findings are discussed, together with important future research issues.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33388983

RESUMO

PURPOSE: To investigate the anatomical features of frontal recess (FR) drainage, and the classification of FR cells and frontal sinus (FS). METHODS: Fifty sides from 30 adult cadaver heads were examined. FR cells and FS along the drainage pathways were dissected under 0° and 70° endoscopic views using unique connecting structures between the uncinate process and the ethmoid bulla as landmarks. RESULTS: Connecting plates between the uncinate process and the ethmoid bulla were discovered and termed medial suprainfundibular plate (MSIP), which were observed on each cadaver head, and lateral suprainfundibular plate (LSIP) on 92% (46/50) sides. Separated by MSIP, two drainage pathways were identified and named medial pathways of the FR (MPFR) medial to the MSIP and the lateral pathways of the FR (LPFR) in the lateral side. Different drainage pathways of the FS were confirmed, in which drained into the MPFR in 37 and into the LPFR in 13 of the cadaver sides. CONCLUSIONS: MSIP is the critical landmark for the recognition of MPFR, LPFR, and the classification of FR cells. The FR resection along LPFR and MPFR facilitated excellent exposure of FS.

11.
Front Oncol ; 10: 560203, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33240809

RESUMO

Purpose: To investigate the risk-stratifying utility of tumor size and a threshold for further stratification on cancer-specific mortality of thyroid cancer (TC) patients in stage IVB. Methods: One thousand three hundred and forty-five patients (620 males and 725 females) with initial distant metastasis over 55 years between 2004 and 2016 from Surveillance, Epidemiology, and End Results databases were investigated, with a median follow-up time of 23 months [interquartile range (IQR), 5-56 months] and a median age of 70 years (IQR, 63-77 years). TC-specific mortality rates were calculated under different classifications. Cox regressions were used to calculate hazard ratios (HRs) and Kaplan-Meier Analyses were conducted to investigate TC-specific survivals. Results: In the whole cohort, patients with tumors >4 cm had the highest TC-specific mortality (67.9%, 330/486), followed by tumor size >1 cm but ≤ 4 cm (43.08%, 190/441), and tumor size ≤ 1 cm (32.69%, 34/104). Kaplan-Meier curves showed the increased tumor size was associated with a statistically significant decrease in TC-specific survival (P < 0.001). Papillary thyroid cancer (PTC) patients with tumors >4 cm had significantly higher hazard ratios (HRs) of 2.84 (1.72-4.70) and 3.11 (1.84-5.26) after adjusting age, gender, race, and radiation treatment, compared with patients with tumors ≤ 1 cm (P < 0.001). The TC-specific mortalities and survivals were further investigated among more detailed subgroups divided by different tumor size, and a threshold of 3 cm could be observed (P < 0.005) for risk stratification. Conclusions: Mortality risk increased with tumor size in PTC patients in stage IVB. Our findings demonstrated the possibility of further stratification in IVB stage in current TNM staging system. Patients with tumor size over 3 cm had an excessively high risk of PTC-specific mortality, which may justify the necessity of more aggressive treatment for them.

12.
Polymers (Basel) ; 12(11)2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33198104

RESUMO

This article demonstrates the one-pot reaction, an efficient and environmentally friendly organic synthesis method, utilized to prepare the silanized silica-encapsulated calcium carbonate@natural rubber composites (SSC@NR), following first mixing the calcium carbonate (CaCO3) solution, silica (SiO2) sol solution and a small amount of Si-69 solution, to modify the surface of CaCO3 particles, and then wet mixing with natural rubber latex. The obtained silanized silica-encapsulated calcium carbonate (SSC) particles were tested by TGA, FTIR and XRD, to substantiate the effect of surface modification. Moreover, the effects of the amount of SSC on the Mooney viscosity, curing characteristics, physical and mechanical properties and dynamic mechanical properties of the SSC@NR were investigated. The results show that the surface of modified CaCO3 is effectively coated with SiO2 particles by means of physical and chemical combination, to achieve the effect of surface coating. When the optimum amount of SSC filler is 40 phr, the SSC can form better physical adsorption and chemical combination with the NR molecular chains and can be evenly dispersed in the rubber matrix, resulting in the conspicuous improvement of physical and mechanical properties, such as the tensile strength, tear strength, elongation at break and abrasion resistance. Meanwhile, the compound with SSC has preferable processability and dynamic mechanical properties.

13.
Int Immunopharmacol ; 88: 106975, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33182046

RESUMO

BACKGROUND: Activated leukocyte cell adhesion molecule (ALCAM) plays an important role in T cell activation and immune response, but the role of ALCAM in allergic rhinitis (AR) remains unclear. The objective of the current study was to validate serum ALCAM as a biomarker in assessing disease severity and predicting the efficacy of sublingual immunotherapy (SLIT) in AR patients. METHODS: We recruited 40 healthy controls (HC group), 38 mild AR patients (MAR group) and 80 moderate-severe AR patients (MSAR group) in this study. Serum levels of ALCAM were determined by ELISA, and the association between ALCAM levels and disease severity was evaluated. In the MSAR group, 68 patients underwent and finished 3-years of SLIT, and were divided into effective group and ineffective group, the relationship between ALCAM levels and efficacy of SLIT was exampled. RESULTS: ALCAM levels were elevated in the serum of AR patients in comparison with HC. Moreover, serum ALCAM concentrations were higher in MSAR group than in MAR group and HC group, and levels of ALCAM significantly correlated with AR total nasal symptom score (TNSS) (r = 0.330, P < 0.001), visual analogue scale (VAS) (r = 0.387, P < 0.001) and serum total IgE levels (r = 0.442, P < 0.001). In the effective group, the ALCAM levels were significantly lower than in the ineffective group. Receiver operating characteristic (ROC) curve exhibited good accuracy for predicting clinical efficacy of SLIT (area under the curve = 0.805, P < 0.001). CONCLUSIONS: The serum ALCAM maybe a novel biomarker for assessing disease severity and predicting clinical efficacy of SLIT in AR patients.

14.
Transp Policy (Oxf) ; 99: 405-418, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32952316

RESUMO

The novel coronavirus 2019 (COVID-19) outbreak has had wide-reaching and unprecedented impacts on the transport sector worldwide. At present, there is no globally agreed timeframe for when this pandemic will end. The current and near-future potential impacts must be addressed in a relatively comprehensive and seamless way. The present study proposed a PASS (P: Prepare-Protect-Provide; A: Avoid-Adjust; S: Shift-Share; S: Substitute-Stop) approach for policymaking that accounts for COVID-19 and future public health threats. The PASS approach was illustrated conceptually, and then policy measures were recommended by referring to the past and ongoing best practices. Policymaking challenges and research issues were discussed.

15.
J Phys Chem Lett ; 11(18): 7782-7789, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32856921

RESUMO

The past decade has witnessed the burgeoning discovery of a variety of topological states of matter with distinct nontrivial band topologies. Thus far, most materials that have been studied possess two-dimensional or three-dimensional electronic structures, with only a few exceptions that host quasi-one-dimensional (quasi-1D) topological electronic properties. Here we present clear-cut evidence for Dirac Fermions in the quasi-1D telluride TaNiTe5. We show that its transport behaviors are highly anisotropic, and we observe nontrivial Berry phases via quantum oscillation measurements. The nontrivial band topology is further corroborated by first-principles calculations. Our results may help to guide the future quest for topological states in this new family of quasi-1D ternary chalcogenides.

16.
Postgrad Med J ; 96(1142): 766-776, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32843482

RESUMO

Trials studying iron administration in patients with chronic heart failure (CHF) and iron deficiency (ID) have sprung up these years but the results remain inconsistent. The aim of this meta-analysis was to comprehensively evaluate the efficacy and safety of iron therapy in patients with CHF and ID. A literature search was conducted across PubMed, Embase, Cochrane Library, OVID and Web of Science up to 31 July 2019 to search for randomised controlled trials (RCT) comparing iron therapy with placebo in CHF with ID, regardless of presence of anaemia. Published studies reporting data of any of the following outcomes were included: all-cause death, cardiovascular hospitalisation, adverse events, New York Heart Association (NYHA) functional class, left ventricular ejection fraction (LVEF), N-terminal pro b-type natriuretic peptide, peak oxygen consumption, 6 min walking test (6MWT) distance and quality of life (QoL) parameters. 15 RCTs with a total of 1627 patients (911 in iron therapy and 716 in control) were included. Iron therapy was demonstrated to reduce the risk of cardiovascular hospitalisation (OR 0.35, 95% CI 0.12 to 0.99, p=0.049), but was ineffective in reducing all-cause death (OR 0.59, 95% CI 0.33 to 1.06, p=0.078) or cardiovascular death (OR 0.80, 95% CI 0.39 to 1.63, p=0.540). Iron therapy resulted in a reduction in NYHA class (mean difference (MD) -0.73, 95% CI -0.99 to -0.47, p<0.001), an increase in LVEF (MD +4.35, 95% CI 0.69 to 8.00, p=0.020), 6MWT distance (MD +35.44, 95% CI 11.55 to 59.33, p=0.004) and an improvement in QoL: EQ-5D score (MD +4.07, 95% CI 0.84 to 7.31, p=0.014); Minnesota Living With Heart Failure Questionnaire score (MD -19.47, 95% CI -23.36 to -15.59, p<0.001) and Patients Global Assessment (PGA) scale (MD 0.71, 95% CI 0.32 to 1.10, p<0.001). There was no significant difference in adverse events or serious adverse events between iron treatment group and control group. Iron therapy reduces cardiovascular hospitalisation in patients with CHF with ID, and additionally improves cardiac function, exercise capacity and QoL in patients with CHF with ID and anaemia, without an increase of adverse events.

17.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 36(5): 457-461, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32696759

RESUMO

This article aims at investigating the feasibility and potential of natural killer (NK) cells to treat corona virus disease 2019 (COVID-19) caused by severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). Through retrospective analysis of existing anti-virus researches and clinical application results of NK cells, and based on the characteristics and properties of this cell, we designed a plan for NK cells to treat COVID-19. As an important part of the immune system, NK cells have clear anti-viral ability. In addition, it also plays the role in immune defense, immune surveillance and immune regulation. Many clinical applications have proved the safety and effectiveness of NK cell application. Currently COVID-19 is highly contagious and harmful to people, and easy to cause irreversible lung damage. Although quarantine can effectively prevent and control viral infections, there is no effective drug treatment available. To avoid further greater losses, it is tremendously necessary to investigate an effective treatment plan.


Assuntos
Infecções por Coronavirus , Células Matadoras Naturais , Pandemias , Pneumonia Viral , Betacoronavirus , Infecções por Coronavirus/terapia , Humanos , Pneumonia Viral/terapia , Estudos Retrospectivos
18.
Infect Immun ; 88(9)2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32540868

RESUMO

C-type lectin receptors (CLRs) play key roles in antifungal defense. CLR-induced NF-κB is central to CLR functions in immunity, and thus, molecules that control the amplitude of CLR-induced NF-κB could profoundly influence host defense against fungal pathogens. However, little is known about the mechanisms that negatively regulate CLR-induced NF-κB, and molecules which act on the CLR family broadly and which directly regulate acute CLR-signaling cascades remain unidentified. Here, we identify the ubiquitin-editing enzyme A20 as a negative regulator of acute NF-κB activation downstream of multiple CLR pathways. Absence of A20 suppression results in exaggerated CLR responses in cells which are A20 deficient and also cells which are A20 haplosufficient, including multiple primary immune cells. Loss of a single allele of A20 results in enhanced defense against systemic Candida albicans infection and prolonged host survival. Thus, A20 restricts CLR-induced innate immune responses in vivo and is a suppressor of host defense against systemic fungal infection.

19.
J Cell Mol Med ; 24(12): 6781-6795, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32363688

RESUMO

Long non-coding RNAs (lncRNAs), which are longer than 200 nt, have been proved to play a role in promoting or inhibiting cancer progression. The following study investigated the role and underlying mechanisms of lncRNA RP11-159K7.2 in laryngeal squamous cell carcinoma (LSCC) progression. Briefly, in situ hybridization (ISH) and real-time quantitative PCR (RT-qPCR) showed higher expression of RP11-159K7.2 in LSCC tissues and cell lines. Patients with low expression level of RP11-159K7.2 lived longer compared to those with high expression of RP11-159K7.2 (χ2  = 39.111, ***P < 0.001). Multivariate Cox regression analysis suggested that lncRNA RP11-159K7.2 was an independent prognostic factor for LSCC patients (HR = 2.961, ***P < 0.001). Furthermore, to investigate the potential involvement of RP11-159K7.2 in the development of LSCC, we knocked out the expression of endogenous RP11-159K7.2 in TU-212 cells and AMC-HN-8 cells via CRISPR/Cas9 double vector lentiviral system. RP11-159K7.2 knockout decreased LSCC cell growth and invasion both in vitro and in vivo. Mechanically, we found that RP11-159K7.2 could positively regulate the expression of DNMT3A by sponging miR-206. In addition, a feedback loop was also discovered between DNMT3A and miR-206. To sum up, these findings suggest that lncRNA RP11-159K7.2 could be used as a potential biomarker for prognosis and treatment of LSCC.

20.
Int Heart J ; 61(3): 553-561, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32418960

RESUMO

Many published studies have evaluated the association between the 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T (rs1801133) polymorphism and the risk of congenital heart disease (CHD); however, the specific conclusion is still controversial.To get a more accurate conclusion, we used a meta-analysis to evaluate the association between the MTHFR gene C677T polymorphism and the risk of CHD.Based on the design-based search strategy, a comprehensive literature search was conducted on PubMed, OVID, Cochrane Library, Embase, Wanfang, CNKI, and Web of Science. We selected the Newcastle-Ottawa Scale (NOS) to assess the quality of the included studies. We performed a heterogeneity test on the results of the study and calculated the combined odds ratios (ORs) and its corresponding 95% confidence intervals (95% CIs) under a random- or fixed-effect model. Subgroup analyses were conducted by ethnicity, source of controls, sample size, and genotyping method. Sensitivity analysis was used to insure authenticity of this meta-analysis result. Egger's test and Begg's funnel plot were performed to detect publication bias.Eventually, our meta-analysis included 15 eligible studies. We observed a significant correlation between the MTHFR C677T polymorphism and the development of CHD in the recessive model (OR: 1.35, 95% CI: 1.06-1.71, P = 0.006) for the overall population. In subgroups stratified by ethnicity and source of controls, subgroup analyses indicated similar associations in Asians and hospital-based groups, but not for Caucasians and population-based groups. Egger's test and Begg's funnel plot demonstrated no significant publication bias in our study.Our analysis identified that MTHFR C677T allele is a risk genetic for CHD development, especially in Asians compared with Caucasians.


Assuntos
Cardiopatias Congênitas/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Predisposição Genética para Doença , Humanos
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