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1.
Sheng Wu Gong Cheng Xue Bao ; 37(2): 663-672, 2021 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-33645164

RESUMO

We developed a high-efficiency microfluidic chip for extracting exosomes from human plasma. We collected peripheral blood from normal human, designed and fabricated a microfluidic chip based on nanoporous membrane and agarose gel electrophoresis to isolate exosomes. The extracted exosomes were characterized by transmission electron microscopy, nanosight and Western blotting, the morphology, concentration and particle size of exosomes were identified and analyzed. Meanwhile, we used ultracentrifugation and microfluidic chip to isolate exosomes separately. The particle size and concentration of the exosomes extracted by two methods were compared and analyzed, and their respective extraction efficiency was discussed. Finally, the expression level of miRNA-21 in exosomes was analyzed by RT-PCR. The microfluidic chip isolated (in 1 hour) high-purity exosomes with size ranging from 30-200 nm directly from human plasma, allowing downstream exosomal miRNA analysis. By comparing with ultracentrifugation, the isolation yield of microfluidic chip was 3.80 times higher than ultracentrifugation when the volume of plasma sample less than 100 µL. The optimized parameters for exosome isolation by gel electrophoresis microfluidic chip were: voltage: 100 V; concentration of agarose gel: 1.0%; flow rate of injection pump: 0.1 mL/h. The gel electrophoresis microfluidic chips could rapidly and efficiently isolate the exosomes, showing great potential in the research of exosomes and cancer biomarkers.


Assuntos
Exossomos , MicroRNAs , Humanos , MicroRNAs/genética , Microfluídica , Plasma , Ultracentrifugação
2.
J Clin Nurs ; 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33656212

RESUMO

AIMS AND OBJECTIVES: To determine whether resilience buffers the deleterious consequences of caregiver burden on quality of life among parents of children with type 1 diabetes. BACKGROUND: The burden of caring for a child with type 1 diabetes can be a form of stress and damage parents' quality of life. Resilience is a crucial psychological variable that contributes to individual health in the context of extraordinary challenges. However, no studies in pediatric diabetes have focused on the effects of parent resilience on caregiving burden and quality of life. DESIGN: This was a descriptive cross-sectional study with a convenience sample following the STROBE guidelines. METHODS: A total of 227 parents were invited to participate during the children's routine outpatient visit. Parents completed measures of resilience, caregiver burden, and quality of life. The disease characteristics of children were extracted from the electronic medical records. We performed hierarchical multiple regression and Johnson-Neyman statistical analysis to probe the moderating effect of resilience. RESULTS: The parents reported poorer mental and physical health as compared with the general population. Caregiver burden was significantly negatively associated with parents' quality of life, while resilience demonstrated a positive correlation with life quality. Resilience served as a moderator between caregiver burden and mental health. When parents experienced a high caregiver burden, the benefit of high resilience for better mental health was apparent. CONCLUSIONS: The present study underscores the protective role of resilience in reducing caregiving burden and improving parents' quality of life. RELEVANCE TO CLINICAL PRACTICE: Regular psychosocial assessment for parents of children with type 1 diabetes should be incorporated into clinical nursing practice. This study confirms that resilience is a promising intervention target for parents with heavy caregiver burden and unsatisfactory life quality.

3.
Nat Commun ; 12(1): 1293, 2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637721

RESUMO

Tendon injuries disrupt the balance between stability and mobility, causing compromised functions and disabilities. The regeneration of mature, functional tendons remains a clinical challenge. Here, we perform transcriptional profiling of tendon developmental processes to show that the extracellular matrix-associated protein periostin (Postn) contributes to the maintenance of tendon stem/progenitor cell (TSPC) functions and promotes tendon regeneration. We show that recombinant periostin (rPOSTN) promotes the proliferation and stemness of TSPCs, and maintains the tenogenic potentials of TSPCs in vitro. We also find that rPOSTN protects TSPCs against functional impairment during long-term passage in vitro. For in vivo tendon formation, we construct a biomimetic parallel-aligned collagen scaffold to facilitate TSPC tenogenesis. Using a rat full-cut Achilles tendon defect model, we demonstrate that scaffolds loaded with rPOSTN promote endogenous TSPC recruitment, tendon regeneration and repair with native-like hierarchically organized collagen fibers. Moreover, newly regenerated tendons show recovery of mechanical properties and locomotion functions.

4.
BMC Nephrol ; 22(1): 51, 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33541266

RESUMO

BACKGROUND: Heterozygous mutations in the inverted formin 2 (INF2) gene are related to secondary focal segmental glomerulosclerosis (FSGS), a rare secondary disease associated with rapidly progressive renal failure. CASE PRESENTATION: We report a patient with familial autosomal INF2 mutation manifesting nephritic syndromes and elevated serum creatinine levels. Mutational analysis revealed an autosomal dominant (AD) inheritance pattern and a mutation in exon 4 (p.Arg214Cys) of INF2 as the likely cause, which has not been previously described in an Asian family. The patient progressed to end-stage renal disease (ESRD) and received hemodialysis. His mother had undergone renal transplant 3 years earlier, and his grandmother had carried the p.Arg214Cys mutation for more than 80 years without any sign of renal dysfunction. CONCLUSIONS: This is the first report to identify an association between a familial autosomal dominant INF2 p.Arg214Cys mutation and rapidly progressive renal disease in an Asian family. INF2 mutation analysis should not be restricted to individuals without family history of FSGS, rather it should also be performed on individuals for whom drug-based therapies are not effective. In this case, kidney transplant is an effective alternative.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33618923

RESUMO

BACKGROUND AND AIMS: Iron deficiency is prevalent, but there is limited data about the relationship between iron status and poor outcomes in chronic kidney disease patients undergoing peritoneal dialysis (PD). We aimed to investigate the association between iron status and mortality in PD patients. METHODS AND RESULTS: This retrospective study was conducted on incident PD patients from January 2006 to December 2016 and followed up until December 2018. Patients were categorized into four groups according to baseline serum transferrin saturation (percent) and ferritin levels (ng/ml): reference (20-30%, 100-500 ng/ml), absolute iron deficiency (<20%, <100 ng/ml), function iron deficiency (FID) (<20%, >100 ng/ml), and high iron (>30%, >500 ng/ml). Among the 1173 patients, 77.5% had iron deficiency. During a median follow-up period of 43.7 months, compared with the reference group, the FID group was associated with increased risk for all-cause [adjusted hazard ratio (aHR) 1.87, 95% confidence interval (95% CI) 1.05-3.31, P = 0.032], but not cardiovascular (CV) mortality. Additionally, the high iron group had a more than four-fold increased risk of both all-cause and CV mortality [aHR 4.32 (95% CI 1.90-9.81), P < 0.001; aHR 4.41 (95% CI 1.47-13.27), P = 0.008; respectively]. CONCLUSION: FID and high iron predict worse prognosis of patients on PD.

6.
J Neural Eng ; 2021 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-33601356

RESUMO

OBJECTIVE: This study proposed and evaluated a channel ensemble approach to enhance detection of steady-state visual evoked potentials (SSVEPs). APPROACH: Collected multi-channel electroencephalogram (EEG) signals were classified into multiple groups of new analysis signals based on correlation analysis, and each group of analysis signals contained signals from a different number of electrode channels. These groups of analysis signals were used as the input of a training-free feature extraction model, and the obtained feature coefficients were converted into feature probability values using the softmax function. The ensemble value of multiple sets of feature probability values was determined and used as the final discrimination coefficient. MAIN RESULTS: Compared with canonical correlation analysis (CCA), likelihood ratio test (LRT), and multivariate synchronization index (MSI) analysis methods using a standard approach, the recognition accuracies of the methods using a channel ensemble approach were improved by 5.05%, 3.87%, and 3.42%, and the information transfer rates (ITRs) were improved by 6.00%, 4.61%, and 3.71%, respectively. The channel ensemble method also obtained better recognition results than the standard algorithm on the public dataset. This study validated the efficiency of the proposed method to enhance the detection of SSVEPs, demonstrating its potential use in practical brain-computer interface (BCI) systems. SIGNIFICANCE: A SSVEP-based BCI system using a channel ensemble method could achieve high ITR, indicating great potential of this design for various applications with improved control and interaction.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33605019

RESUMO

Efficient coupling solar energy conversion and N2 fixation by photocatalysis has been shown promising potentials. However, the unsatisfied yield rate of NH3 curbs its forward application. Herein, defective typical perovskite, BaTiO3 , shows remarkable activity under an applied magnetic field for photocatalytic N2 fixation with the NH3 yield rate exceeding 1.90mg/L/h. Through steered surface spin states and oxygen vacancies, the electromagnetic synergistic effect between the internal electric field and an external magnetic field is stimulated. X-ray absorption structure (XAS) spectrum and density functional theory (DFT) calculations reveal the regulation of electronic and magnetic properties through manipulations of oxygen vacancies and inducements of Lorentz force and spin selectivity effect. The electromagnetic synergistic effect suppresses the recombination of photoexcited carriers in semiconducting nanomaterials, which acts synergistically to promote N2 adsorption and activation while facilitating fast charge separation under UV-vis irradiation. Therefore, this work offers a promising alternative route for exploring high-photocatalytic-property N2 fixation materials and shed light on stimulating the development of synergistic effect in photocatalysts.

8.
J Healthc Eng ; 2021: 6611196, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33628402

RESUMO

The development of virtual reality technology is expected to solve traditional surgical training. The lack of methods has brought revolutionary advances in technology. The virtual surgery system based on collision detection and force feedback can enable the operator to have stronger interaction, which is an exploration of the feature of touch in virtual reality technology. Reality is an important indicator of the virtual surgical system. This article improves the realism of the system from the visual and tactile senses and uses the surrounding ball collision detection and force feedback algorithms to build a realistic surgical platform. In the virtual surgery training system, the introduction of force feedback greatly improves the sense of presence during virtual surgery interaction. The operator can feel the softness and hardness of different tissues and organs through the force feedback device. Virtual reality is an interdisciplinary comprehensive technology that has been widely used in military, film, medical, and gaming fields. Virtual reality can simulate the objective world and display it visually, making people feel immersive. Virtual surgery provides surgeons with a recyclable surgical practice platform and can help doctors perform preoperative rehearsals and predict the results of surgery. The design of collision detection and force feedback algorithms is a prerequisite to ensure the immersion and transparency of the virtual surgical training system. This article mainly introduces the collision detection and force feedback algorithm research in virtual surgery, with the intention of providing some ideas and directions for the development of virtual surgery. This paper proposes two collision detection algorithms, space decomposition method and hierarchical bounding box method, and three force feedback algorithms including spring mass point algorithm, Runge-Kutta method, and Euler method to construct virtual surgery collision detection and force feedback. Experiment with the Overall System Architecture. This paper proves through experimental results that the average collision detection time after the application of the improved collision detection and force feedback algorithm in the virtual surgery system is more than 80.7% less than the traditional method, which greatly improves the detection speed.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33538592

RESUMO

The development of high-efficiency oxygen electrocatalysts with earth-abundant transition metals rather than scarce noble metals has aroused growing interests due to their potential for energy storage and conversion applications. Herein, we developed a facile strategy to synthesize hollow tubular bimetallic Ni-Co oxide rooted with dense nanosheets for enhanced bifunctionality and facilitated redox reaction kinetics. Owing to the rational design of morphology and well-dispersed Ni and Co ions, the bimetallic samples exhibit admirable bifunctional electrocatalytic activities. This bimetallic Ni-Co oxide shows superior oxygen electrocatalytic performance in comparison with the monometallic Ni and Co oxides, according to the electrocatalytic synergistic effect from the bimetallic system. The optimized sample with the specific mass ratio of Ni and Co displays the oxygen reduction reaction (ORR) property comparable to commercial Pt/C and oxygen evolution reaction (OER) performance superior to commercial RuO2. The electrochemical tests and structural characterizations offer in-depth dissection on the electrocatalytic behaviors, especially the superb stability in both ORR and OER tests, as well as the outstanding resistance to methanol poisoning, representing a promising candidate in the renewable energy field.

10.
Clin Rheumatol ; 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33411142

RESUMO

OBJECTIVES: To evaluate the demographics, clinical aspects, and major organ involvement of patients with late-onset Behçet's syndrome (BS) in a tertiary center in China. METHODS: We conducted a cross-sectional study of consecutive BS patients in Huadong Hospital of Fudan University from September 2012 to January 2020. We compared clinical variables between patients with disease onset before and after 40 years of age. The relative risks (RRs) of clinical variables were calculated between the two age groups. Moreover, a hierarchical cluster analysis was conducted according to 29 variables to determine homogeneous subgroups in patients with late-onset BS. RESULTS: We enrolled 152 late-onset BS patients, with a median age at onset of 47 years (interquartile range, IQR: 43-52 years). There is a higher prevalence of intestinal ulcers in late-onset BS than in early-onset BS (RR 1.47), but a lower prevalence of ocular involvements (RR 0.54) and folliculitis (RR 0.46). Female sex was associated with genital ulcers, erythema nodosum, and arthritis. Four clusters (C1-C4) were formed. C1 (n = 71), the largest cluster, was defined as the mucocutaneous group, C2 (n = 20) as the arthritis group, C3 (n = 39) as the gastrointestinal group, in which all patients presented with intestinal lesions, and five cases with esophageal ulcers. In C4 (n = 22), showing a mixture of uveitis and vascular lesions, 15 patients presented with uveitis and 8 had vascular lesions, and 1 case had central nervous system lesions. CONCLUSION: Four phenotype clusters were identified. Patients with skin lesions comprised the largest cluster, while gastrointestinal, panuveitis, and cardiovascular clusters are the most commonly involved organs in late-onset BS patients. Key Points • Our analysis demonstrated the phenotype discrepancy between early and late onset groups. • Four phenotype clusters were identified, with gastrointestinal, panuveitis and cardiovascular clusters representing commonly involved organs.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33398902

RESUMO

Tensile-strained Mxene/carbon nanotube (CNT) porous microspheres were developed as an electrocatalyst for the lithium polysulfide (LiPS) redox reaction. The internal stress on the surface results in lattice distortion with expanding Ti-Ti bonds, endowing the Mxene nanosheet with abundant active sites and regulating the d-band center of Ti atoms upshifted closer to the Fermi level, leading to strengthened LiPS adsorbability and accelerated catalytic conversion. The macroporous framework offers uniformed sulfur distribution, potent sulfur immobilization, and large surface area. The composite interwoven by CNT tentacle enhances conductivity and prevents the restacking of Mxene sheets. This combination of tensile strain effect and hierarchical architecture design results in smooth and favorable trapping-diffusion-conversion of LiPS on the interface. The Li-S battery exhibits an initial capacity of 1451 mAh g-1 at 0.2 C, rate capability up to 8 C, and prolonged cycle life.

12.
Nat Commun ; 12(1): 186, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33420036

RESUMO

Stable solid electrolyte interface (SEI) is highly sought after for lithium metal batteries (LMB) owing to its efficient electrolyte consumption suppression and Li dendrite growth inhibition. However, current design strategies can hardly endow a multifunctional SEI formation due to the non-uniform, low flexible film formation and limited capability to alter Li nucleation/growth orientation, which results in unconstrained dendrite growth and short cycling stability. Herein, we present a novel strategy to employ electrolyte additives containing catechol and acrylic groups to construct a stable multifunctional SEI by in-situ anionic polymerization. This self-smoothing and robust SEI offers multiple sites for Li adsorption and steric repulsion to constrain nucleation/growth process, leading to homogenized Li nanosphere formation. This isotropic nanosphere offers non-preferred Li growth orientation, rendering uniform Li deposition to achieve a dendrite-free anode. Attributed to these superiorities, a remarkable cycling performance can be obtained, i.e., high current density up to 10 mA cm-2, ultra-long cycle life over 8500 hrs operation, high cumulative capacity over 4.25 Ah cm-2 and stable cycling under 60 °C. A prolonged lifespan can also be achieved in Li-S and Li-LiFePO4 cells under lean electrolyte content, low N/P ratio or high temperature conditions. This facile strategy also promotes the practical application of LMB and enlightens the SEI design in related fields.

13.
BMC Med Genomics ; 14(1): 14, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407483

RESUMO

BACKGROUND: The role(s) of epigenetic reprogramming in gastric cancer (GC) remain obscure. This study was designed to identify methylated gene markers with prognostic potential for GC. METHODS: Five datasets containing gene expression and methylation profiles from GC samples were collected from the GEO database, and subjected to meta-analysis. All five datasets were subjected to quality control and then differentially expressed genes (DEGs) and differentially expressed methylation genes (DEMGs) were selected using MetaDE. Correlations between gene expression and methylation status were analysed using Pearson coefficient correlation. Then, enrichment analyses were conducted to identify signature genes that were significantly different at both the gene expression and methylation levels. Cox regression analyses were performed to identify clinical factors and these were combined with the signature genes to create a prognosis-related predictive model. This model was then evaluated for predictive accuracy and then validated using a validation dataset. RESULTS: This study identified 1565 DEGs and 3754 DEMGs in total. Of these, 369 were differentially expressed at both the gene and methylation levels. We identified 12 signature genes including VEGFC, FBP1, NR3C1, NFE2L2, and DFNA5 which were combined with the clinical data to produce a novel prognostic model for GC. This model could effectively split GC patients into two groups, high- and low-risk with these observations being confirmed in the validation dataset. CONCLUSION: The differential methylation of the 12 signature genes, including VEGFC, FBP1, NR3C1, NFE2L2, and DFNA5, identified in this study may help to produce a functional predictive model for evaluating GC prognosis in clinical samples.

14.
BMC Public Health ; 21(1): 79, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413224

RESUMO

BACKGROUND: About 83,000 COVID-19 patients were confirmed in China up to May 2020. Amid the well-documented threats to physical health, the effects of this public health crisis - and the varied efforts to contain its spread - have altered individuals' "normal" daily functioning. These impacts on social, psychological, and emotional well-being remain relatively unexplored - in particular, the ways in which Chinese men and women experience and respond to potential behavioral stressors. Our study investigated sex differences in psychological stress, emotional reactions, and behavioral responses to COVID-19 and related threats among Chinese residents. METHODS: In late February (2020), an anonymous online questionnaire was disseminated via WeChat, a popular social media platform in China. The cross-sectional study utilized a non-probabilistic "snowball" or convenience sampling of residents from various provinces and regions of China. Basic demographic characteristics (e.g., age and gender) - along with residential living arrangements and conditions - were measured along with psychological stress and emotional responses to the COVID-19 pandemic. RESULTS: Three thousand eighty-eight questionnaires were returned: 1749 females (56.6%) and 1339 males (43.4%). The mean stress level,as measured by a visual analog scale, was 3.4 (SD = 2.4) - but differed significantly by sex. Besides sex, factors positively associated with stress included: age (< 45 years), employment (unsteady income, unemployed), risk of infection (exposureto COVID-19, completed medical observation), difficulties encountered (diseases, work/study, financial, mental), and related behaviors (higher desire for COVID-19 knowledge, more time concerning on the COVID-19 outbreak). "Protective" factors included frequent contact with colleagues, calmness of mood comparing with the pre-pandemic, and psychological resilience. Males and females also differed significantly in adapting to current living/working, conditions, responding to run a fever, and needing psychological support services. CONCLUSIONS: The self-reported stress of Chinese residents related to the COVID-19 pandemic was significantly related to sex, age, employment, resilience and coping styles. Future responses to such public health threats may wish to provide sex- and/or age-appropriate supports for psychological health and emotional well-being to those at greatest risk of experiencing stress.


Assuntos
Adaptação Psicológica , Emprego/psicologia , Resiliência Psicológica , Fatores Sexuais , Estresse Psicológico/psicologia , Adulto , Fatores Etários , China/epidemiologia , Estudos Transversais , Surtos de Doenças , Emoções , Emprego/estatística & dados numéricos , Feminino , Humanos , Masculino , Saúde Mental , Serviços de Saúde Mental , Pessoa de Meia-Idade , Determinação de Necessidades de Cuidados de Saúde , Pandemias , Fatores de Risco , Estresse Psicológico/epidemiologia , Inquéritos e Questionários
15.
Phytother Res ; 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33440458

RESUMO

Our previous study revealed that Epimedii Folium (EF) and Codonopsis Radix (CNR) significantly promoted tumor growth on a subcutaneous mouse model of prostate cancer (PCa) via enhancing the mRNA and protein expressions of androgen receptor (AR), while Astragali Radix (AGR) inhibited tumor growth via suppressing the protein expression of AR. In the present study, we aimed to investigate the potential interactions between EF, CNR or AGR and AR antagonist (abiraterone acetate [ABI]) on the tumor growth using subcutaneous and orthotopic PCa mouse models. EF, CNR, AGR and ABI were intragastrically given to mice once every 2 days for 4 weeks. The pharmacokinetics of ABI were evaluated in the plasma of rats when combined with EF, CNR, or AGR. Our results demonstrated that EF or CNR could weaken the anti-tumor effects of ABI via increasing the AR expression involving activation of the PI3K/AKT and Rb/E2F pathways and decreasing the bioavailability of ABI, while AGR could enhance the anti-tumor effects of ABI through suppressing the AR expression via inhibiting the activations of PI3K/AKT and Rb/E2F pathways and increasing the bioavailability of ABI. These findings imply that cautions should be exercised when prescribing EF and CNR for PCa patients.

16.
BMC Bioinformatics ; 22(1): 17, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413089

RESUMO

BACKGROUND: Querying drug-induced gene expression profiles with machine learning method is an effective way for revealing drug mechanism of actions (MOAs), which is strongly supported by the growth of large scale and high-throughput gene expression databases. However, due to the lack of code-free and user friendly applications, it is not easy for biologists and pharmacologists to model MOAs with state-of-art deep learning approach. RESULTS: In this work, a newly developed online collaborative tool, Genetic profile-activity relationship (GPAR) was built to help modeling and predicting MOAs easily via deep learning. The users can use GPAR to customize their training sets to train self-defined MOA prediction models, to evaluate the model performances and to make further predictions automatically. Cross-validation tests show GPAR outperforms Gene set enrichment analysis in predicting MOAs. CONCLUSION: GPAR can serve as a better approach in MOAs prediction, which may facilitate researchers to generate more reliable MOA hypothesis.


Assuntos
Inteligência Artificial , Farmacologia , Software , Transcriptoma/genética , Biologia Computacional , Bases de Dados Genéticas , Preparações Farmacêuticas
17.
Appl Microbiol Biotechnol ; 105(4): 1365-1377, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33492451

RESUMO

Cyclophilin A (CypA), a key member of the immunophilin family, is the most abundantly expressed isozyme of the 18 known human cyclophilins. Besides acting as an intracellular receptor for cyclosporine A, CypA plays a vital role in microorganismal infections, cardiovascular diseases, liver diseases, kidney diseases, neurodegeneration, cancer, rheumatoid arthritis, periodontitis, sepsis, asthma, and aging. This review focuses on the pivotal roles of CypA in the infection of etiological agents, which manifests mainly in promoting or inhibiting viral replication based on the host cell type and viral species. CypA can interact with viral proteins and thus regulate the replication cycle of the virus. CypA is involved in pathogenic bacterial infections by regulating the formation of host actin skeleton or membrane translocation of bacterial toxins, or mediated the adhesion of Mycoplasma genitalium during the infection processes by acting as a cellular receptor of M. genitalium. CypA also plays a critical role in infection or the life cycle of certain parasites or host immune regulation. Moreover, we summarized the current understanding of CypA inhibitors acting as host-targeting antiviral agents, thus opening an avenue for the treatment of multiple viral infections due to their broad antiviral effects and ability to effectively prevent drug resistance. Therefore, the antiviral effect of CypA has the potential to promote CypA inhibitors as host-targeting drugs to CypA-involved etiological agent infections and human diseases. KEY POINTS: • CypA is involved in the replication and infection of several viruses, pathogenic bacteria, mycoplasma, and parasites. • CypA inhibitors are in a strong position to inhibit the infection of viruses, bacterial, and mycoplasma.

18.
Ecotoxicol Environ Saf ; 211: 111881, 2021 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-33444878

RESUMO

BACKGROUND: Cadmium is the most prevalent form of heavy metal contaminant globally and its exposure rises serious health concern. Chronic exposure to cadmium causes immune disturbances. However, few studies have addressed how it affects circulating immune cells, one of the most essential elements for the host defense system, at both population and molecular level. Therefore, this is the first single-cell transcriptomic analysis of the response of the human circulating immune system to plasma cadmium level. METHODS: We conducted a cross-sectional study in Hunan province, which has the highest level of cadmium land contamination in China. A total of 3283 individuals were eligible for analyzing the association between plasma cadmium levels and the monocyte counts and its subgroups. Another 780 individuals were assigned for validation. Thirty propensity-matched individuals without chronic disease from the lowest- and highest-quartile groups according to serum cadmium levels were selected for single-cell RNA sequencing (scRNA-seq) and flow cytometry analyses. Moreover, the monocyte phenotypic alterations in the heavy metal-exposed population were validated with a cecal ligation and puncture sepsis mouse model. RESULTS: From August 2016 to July 2017, we conducted a cross-sectional study to identify phenotypic alterations in peripheral immune cells in cadmium polluted areas in China. Monocyte percentages were negatively associated with plasma cadmium levels in multivariable linear regression analysis. Peripheral blood mononuclear cell scRNA-seq revealed that the CD14+ monocyte subset was dramatically reduced in the highest-quartile cadmium-exposed group. Moreover, we assessed different hallmarks of immune cell dysfunction-such as host defense capability, apoptotic signaling, cellular diversity and malignant gene expression in monocytes. Importantly, cadmium induced phenotypic alterations in the immune system were validated in the cecal ligation and puncture sepsis mouse model, in which chronic exposure to cadmium not only increased the death rate but also decreased monocyte numbers and the ability to clear bacterial infections. CONCLUSION: This transcriptomic analysis provides molecular information about how the most important hallmarks of immune cell dysfunction are affected by plasma cadmium level. The significant phenotypic alterations in monocytes serving as early indicators of increased susceptibility to infectious and malignant diseases.


Assuntos
Cádmio/toxicidade , Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/toxicidade , Monócitos/efeitos dos fármacos , China , Estudos Transversais , Citometria de Fluxo , Humanos , Contagem de Leucócitos , Leucócitos Mononucleares , Masculino , Monócitos/citologia , Transcriptoma
19.
Cell Cycle ; 20(3): 320-331, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33461373

RESUMO

Triple-negative breast cancer (TNBC) is the most aggressive histological subtype of breast cancer and is characterized by poor outcomes and a lack of specific-targeted therapies. Transforming growth factor-ß (TGF-ß) acts as the key cytokine in the epithelial-mesenchymal transition (EMT) and the metastasis of TNBC. However, the regulatory mechanisms of the TGF-ß signaling pathway remain largely unknown. In this study, we identified that the USP1/WDR48 complex could effectively enhance TGF-ß-mediated EMT and migration of TNBC cells. Furthermore, lower phosphorylation of Smad2/3, Erk, Jnk, and p38 was noted on the suppression of the expression of endogenous USP1 or WDR48. Moreover, the USP1-WDR48 complex was found to downregulate the polyubiquitination of TAK1 and mediate its in vitro stability. Therefore, our findings have shed a light on the novel role of the USP1/WDR48 complex in promoting TGF-ß-induced EMT and migration in TNBC via in vitro stabilization of TAK1.

20.
Environ Health ; 20(1): 9, 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33468146

RESUMO

BACKGROUND: In August 2017, Hurricane Harvey caused unprecedented flooding across the greater Houston area. Given the potential for widespread flood-related exposures, including mold and sewage, and the emotional and mental toll caused by the flooding, we sought to evaluate the short- and long-term impact of flood-related exposures on the health of Houstonians. Our objectives were to assess the association of flood-related exposures with allergic symptoms and stress among Houston-area residents at two time points: within approximately 30 days (T1) and 12 months (T2) after Hurricane Harvey's landfall. METHODS: The Houston Hurricane Harvey Health (Houston-3H) Study enrolled a total of 347 unique participants from four sites across Harris County at two times: within approximately 1-month of Harvey (T1, n = 206) and approximately 12-months after Harvey (T2, n = 266), including 125 individuals who participated at both time points. Using a self-administered questionnaire, participants reported details on demographics, flood-related exposures, and health outcomes, including allergic symptoms and stress. RESULTS: The majority of participants reported hurricane-related flooding in their homes at T1 (79.1%) and T2 (87.2%) and experienced at least one allergic symptom after the hurricane (79.4% at T1 and 68.4% at T2). In general, flood-exposed individuals were at increased risk of upper respiratory tract allergic symptoms, reported at both the T1 and T2 time points, with exposures to dirty water and mold associated with increased risk of multiple allergic symptoms. The mean stress score of study participants at T1 was 8.0 ± 2.1 and at T2, 5.1 ± 3.2, on a 0-10 scale. Participants who experienced specific flood-related exposures reported higher stress scores when compared with their counterparts, especially 1 year after Harvey. Also, a supplementary paired-samples analysis showed that reports of wheezing, shortness of breath, and skin rash did not change between T1 and T2, though other conditions were less commonly reported at T2. CONCLUSION: These initial Houston-3H findings demonstrate that flooding experiences that occurred as a consequence of Hurricane Harvey had lasting impacts on the health of Houstonians up to 1 year after the hurricane.

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