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1.
Artigo em Inglês | MEDLINE | ID: mdl-34472168

RESUMO

Developing endogenous photo-activated theranostic platform to overcome the limitation of low tissue-penetration from external photo-excitation for precise cancer diagnosis and treatment is highly significant but remains huge challenge. Here, as a proof of concept, we report a hydrogen peroxide (H 2 O 2 )-initiated chemiluminescence triggered nanoparticles aggregation (HICTNA) strategy to activate the theranostic functions of gold nanoparticles (AuNPs) for specific visualization and effective therapy of tumors. A pair of small AuNPs, namely tAuNP and mAuNP, were rationally designed and fabricated by conjugating 2,5-diphenyltetrazole (Tz) and methacrylic acid (Ma) onto the surface of particles, respectively. The mAuNP nanoparticles were absorbed with luminescent substrate luminol through electrostatic interaction to afford self-illuminating nanoparticles mAuNP/Lu that could produce strong chemiluminescence (CL) under the catalysis of H 2 O 2 in tumor microenvironment. Taking advantage of the well-known tetrazole/alkene "photo-click" cycloaddition, significant aggregation of AuNPs was simultaneously triggered by endogenous CL resulting in enhanced tumorous accumulation and retention of AuNPs for activated photoacoustic imaging (PAI) and photothermal therapy (PTT) of tumors in vivo . We thus believe that this HICTNA concept may offer an attractive and universal tool to improve the diagnostic and therapeutic efficacy of nanomedicine for achieving precise cancer treatment.

2.
Acta Biomater ; 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34481053

RESUMO

The leaflets of the atrioventricular heart valves (AHVs) regulate the one-directional flow of blood through a coordination of the extracellular matrix components, including the collagen fibers, elastin, and glycosaminoglycans. Dysfunction of the AHVs, such as those caused by unfavorable microstructural remodeling, lead to valvular heart diseases and improper blood flow, which can ultimately cause heart failure. In order to better understand the mechanics and remodeling of the AHV leaflets and how therapeutics can inadvertently cause adverse microstructural changes, a systematic characterization of the role of each constituent in the biomechanical properties is appropriate. Previous studies have quantified the contributions of the individual microstructural components to tissue-level behavior for the semilunar valve cusps, but not for the AHV leaflets. In this study, for the first time, we quantify the relationships between microstructure and mechanics of the AHV leaflet using a three-step experimental procedure: (i) biaxial tension and stress relaxation testing of control (untreated) porcine AHV anterior leaflet specimens; (ii) enzyme treatment to remove a portion of either the collagen or elastin constituent; and (iii) biaxial tensile and stress relaxation testing of the constituent-removed (treated) specimens. We have observed that the removal of ∼100% elastin resulted in a ∼10% decrease in the tissue extensibility with biaxial tension and a ∼10% increase in the overall stress reduction with stress relaxation. In contrast, removal of 46% of the collagen content insignificantly affected tissue extensibility with biaxial tension and significantly increased stress decay (10%) with stress relaxation. These findings provide an insight into the microstructure-mechanics relationship of the AHVs and will be beneficial for future developments and refinements of microstructurally informed constitutive models for the simulation of diseased and surgically intervened AHV function. STATEMENT OF SIGNIFICANCE: This study presents, for the first time, a thorough mechanical characterization of the atrioventricular heart valve leaflets before and after enzymatic removal of elastin and collagen. We found that the biaxial tensile properties of elastin-deficient tissues and collagen-deficient are stiffer. The fact of elastin supporting low-stress valve function and collagen as the main load-bearing component was evident in a decrease in the low-tension modulus for elastin-deficient tissues and in the high-tension modulus for collagen-deficient tissues. Our quantification and experimental technique could be useful in predicting the disease-related changes in heart valve mechanics. The information obtained from this work is valuable for refining the constitutive models that describe the essential microstructure-mechanics relationship.

3.
J Microbiol ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34491523

RESUMO

Streptococcus suis serotype 2 (S. suis 2) is an important zoonotic pathogen that presents a significant threat both to pigs and to workers in the pork industry. The initial steps of S. suis 2 pathogenesis are unclear. In this study, we found that the type II histidine triad protein HtpsC from the highly virulent Chinese isolate 05ZYH33 is structurally similar to internalin A (InlA) from Listeria monocytogenes, which plays an important role in mediating listerial invasion of epithelial cells. To determine if HtpsC and InlA function similarly, an isogenic htpsC mutant (ΔhtpsC) was generated in S. suis by homologous recombination. The htpsC deletion strain exhibited a diminished ability to adhere to and invade epithelial cells from different sources. Double immunofluorescence microscopy also revealed reduced survival of the ΔhtpsC mutant after co-cultivation with epithelium. Adhesion to epithelium and invasion by the wild type strain was inhibited by a monoclonal antibody against E-cadherin. In contrast, the htpsC-deficient mutant was unaffected by the same treatment, suggesting that E-cadherin is the host-cell receptor that interacts with HtpsC and facilitates bacterial internalization. Based on these results, we propose that HtpsC is involved in the process by which S. suis 2 penetrates host epithelial cells, and that this protein is an important virulence factor associated with cell adhesion and invasion.

4.
Eur J Med Chem ; 225: 113818, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34492551

RESUMO

Cathepsin C, an important lysosomal cysteine protease, mediates the maturation process of neutrophil serine proteases, and participates in the inflammation and immune regulation process associated with polymorphonuclear neutrophils. Therefore, cathepsin C is considered to be an attractive target for treating inflammatory diseases. With INS1007 (trade name: brensocatib) being granted a breakthrough drug designation by FDA for the treatment of Adult Non-cystic Fibrosis Bronchiectasis and Coronavirus Disease 2019, the development of cathepsin C inhibitor will attract attentions from medicinal chemists in the future soon. Here, we summarized the research results of cathepsin C as a therapeutic target, focusing on the development of cathepsin C inhibitor, and provided guidance and reference opinions for the upcoming development boom of cathepsin C inhibitor.

5.
Biochim Biophys Acta Mol Basis Dis ; : 166268, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536536

RESUMO

OBJECTIVE: Treatment of acute myeloid leukemia (AML) remains a challenge. It is urgent to understand the microenvironment to improve therapy and prognosis. METHODS: Bioinformatics methods were used to analyze transcription expression profile of AML patient samples with complete clinical information from UCSC Xena TCGA-AML datasets and validate with GEO datasets. Western blot, qPCR, RNAi and CCK8 assay were used to assay the effect of GPX1 expression on AML cell viability and the expression of genes of interest. RESULTS: Our analyses revealed that highly expressed GPX1 in AML patients links to unfavorable prognosis. GPX1 expression was positively associated with not only fraction levels of myeloid-derived suppressor cells (MDSCs), monocytes and T cell exhaustion, the expression levels of MDSC markers, MDSC-promoting CCR2 and immune inhibitory checkpoints (TIM3/Gal-9, SIRPα and VISTA), but also negatively with low fraction levels of CD4+ and CD8+ T cells. Silencing GPX1 expression reduced AML cell viability and CCR2 expression. Moreover, GPX1-targetd kinases were PKC family, SRC family, SYK and PAK1, which promote AML progression and the resistance to therapy. Furthermore, Additionally, GPX1-associated prognostic signature (GPS) is an independent risk factor with high area under curve (AUC) values of receiver operating characteristic (ROC) curves. High risk group based on GPS enriched not only with endocytosis which transfers mitochondria to favor AML cell survival in response to chemotherapy, but also NOTCH,WNT and TLR signaling which promote therapy resistance. CONCLUSION: Our results revealed the significant involvement of GPX1 in AML immunosuppression via and provided a prognostic signature for AML patients.

6.
Photodiagnosis Photodyn Ther ; : 102536, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536605

RESUMO

Seborrheic keratosis (SK) is a common benign lesion in which malignancies like cutaneous squamous cell carcinoma (cSCC) can arise rarely. We report a case of an 81-year-old man who presented a well-demarcated reddish-brown plaque with central raised coarse nodules on the top of his head. Dermoscopy and reflectance confocal microscopy (RCM) showed the possibility of malignant transformation. cSCC was confirmed by histopathology and immunohistochemistry. Considering the fact of local low-risk cSCC within a large SK lesion, carbon dioxide (CO2) laser was used to treat the SK lesion, and reduce the thickness of local cSCC simultaneously. Three sessions of 5-aminolevulinic acid-mediated photodynamic therapy (ALA-PDT) were performed after CO2 laser. Finally, no atypical cells were found by multi-point biopsy after treatment, and follow-up was continued for one year. Therefore, malignant changes of SK are relatively uncommon, but should be suspected when abnormal appearance or symptoms occurred. ALA-PDT combined with CO2 is a safe, effective, and minimally invasive treatment for cSCC arising from a huge SK.

7.
Front Immunol ; 12: 668974, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539623

RESUMO

Objectives: This aim of this study was to determine whether neutrophil extracellular traps (NETs) are involved in the pathogenesis of IgA vasculitis (IgAV) and investigate whether the circulating NETs levels are associated with disease activity in children. Methods: We performed a case-control study and collected blood samples from 193 children with different stages of IgAV (61 were at the onset stage, 64 at the remission stage, 43 at the active stage, and 25 were undergoing drug withdrawal). A total of 192 healthy children were recruited as controls. Circulating cell free DNA (cf-DNA) was obtained from the plasma and quantified by using the Quant-iT PicoGreen DNA quantification kit. NETs-associated myeloperoxidase-DNA (MPO-DNA), citrullinated-histone H3 (cit-H3), neutrophil elastase (NE), and the deoxyribonuclease I (DNase I) concentrations were measured using enzyme-linked immunosorbent assays. The presence of NETs in the kidney and gastrointestinal tissues of onset and active IgAV patients was determined by multiple immunofluorescence staining in 15 IgAV nephritis patients and 9 IgAV patients without IgAV nephritis, respectively. NETs degradation potency of collected sera samples from IgAV patients were checked in vitro. Relationships between circulating levels of cf-DNA with MPO-DNA, NE, and DNase I and the patients were analyzed. Results: Circulating levels of cf-DNA in onset and active IgAV patients were significantly higher than those in remission and drug withdrawal patients as well as healthy controls. The results were similar for MPO-DNA and NE. The levels of circulating cf-DNA correlated significantly with MPO-DNA, NE and DNase I. A significantly decreased degradation of NETs from the onset and active IgAV patients was observed, but was normal in healthy controls. Furthermore, presence of NETs was also confirmed in all renal and gastrointestinal tissues obtained from the onset and active IgAV patients but not control samples. Conclusions: Our data showed that NETs were released into the circulation of IgAV patients and are involved in the disease activity. The circulating levels of NETs maybe used to assess disease severity in children with IgAV.

8.
J Environ Manage ; 300: 113710, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34509811

RESUMO

The application of green reductant is signification to recycling of cathode materials from spent lithium ions batteries. Here, ginkgo biloba was developed for enhancing leaching of spent LiNi0.6Co0.2Mn0.2O2 materials with systematically analysis of leaching kinetics and interface reaction. The leaching efficiencies of Ni, Mn, Co, and Li reach respectively 98.65 %, 98.25 %, 98.41 % and 99.99 % under optimal condition of 1.8 mol/L H2SO4 concentration, 9 g/L ginkgo biloba, 80 °C leaching temperature, 40 min time and 15 g/L pulp density. The apparent activation energies for leaching of Ni, Co, Mn and Li determined as 74.63, 79.33, 73.14 and 23.43 kJ/mol, respectively, indicates that the leaching process was controlled by the surface chemical reaction during the leaching process. Meanwhile, the regenerated material with better electrochemical performance was obtained by co-precipitation and calcination from leachate. Finally, the process is environmental friendly and economical feasible for recycling of spent lithium-ion batteries.

9.
J Surg Oncol ; 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34494280

RESUMO

BACKGROUND AND OBJECTIVES: This study aimed to compare outcomes between neoadjuvant imatinib and upfront surgery in patients with localized rectal gastrointestinal stromal tumors (GIST) patients. METHODS: Eighty-five patients with localized rectal GIST were divided into two groups: upfront surgery ± adjuvant imatinib (Group A, n = 33) and the neoadjuvant imatinib + surgery + adjuvant imatinib (Group B, n = 52). Baseline characteristics between groups were controlled for with inverse probability of treatment weighting (IPTW) adjusted analysis. RESULTS: The response rate to neoadjuvant imatinib was 65.9%. After the IPTW-adjusted analysis, patients who underwent neoadjuvant therapy had better distant recurrence-free survival (DRFS) and disease-specific survival (DSS) compared with those who underwent upfront surgery (5-year DRFS 97.8 vs. 71.9%, hazard ratio [HR], 0.15; 95% CI, 0.03-0.87; p = 0.03; 5-year DSS 100 vs. 77.1%; HR, 0.11; 95% CI, 0.01-0.92; p = 0.04). While no significant association was found between overall survival (OS) and treatment groups (p = 0.07), 5-year OS was higher for the neoadjuvant group than upfront surgery group (97.8% vs. 71.9%; HR, 0.2; 95% CI, 0.03-1.15). CONCLUSIONS: In patients with localized rectal GIST, neoadjuvant imatinib not only shrunk the tumor size but also decreased the risk of metastasis and tumor-related deaths when compared to upfront surgery and adjuvant imatinib alone.

10.
BMC Cancer ; 21(1): 1007, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34496797

RESUMO

BACKGROUND: Cancer-testis antigens (CTAs) and tumour-associated antigens (TAAs) are frequently expressed in hepatocellular carcinoma (HCC); however, the role of tumour-antigen-specific T cell immunity in HCC progression is poorly defined. We characterized CTA- and TAA-specific T cell responses in different HCC stages and investigated their alterations during HCC progression. METHODS: Fifty-eight HCC patients, 15 liver cirrhosis patients, 15 chronic hepatitis B patients and 10 heathy controls were enrolled in total. IFN-γ ELSPOT using CTAs, including MAGE-A1, MAGE-A3, NY-ESO-1, and SSX2, and two TAAs, SALL4 and AFP, was performed to characterize the T-cell immune response in the enrolled individuals. The functional phenotype of T cells and the responsive T cell populations were analyzed using short-term T-cell culture. RESULTS: T cell responses against CTAs and TAAs were specific to HCC. In early-stage HCC patients, the SALL4-specific response was the strongest, followed by MAGE-A3, NY-ESO-1, MAGE-A1 and SSX2. One-year recurrence-free survival after transcatheter arterial chemoembolization plus radiofrequency ablation treatment suggested the protective role of CTA-specific responses. The four CTA- and SALL4-specific T cell responses decreased with the progression of HCC, while the AFP-specific T cell response increased. A higher proportion of CD4+ T cells specific to CTA/SALL4 was observed than AFP-specific T cell responses. CONCLUSIONS: The IFN-γ ELISPOT assay characterized distinct profiles of tumour-antigen-specific T cell responses in HCC patients. CTA- and SALL4-specific T cell responses may be important for controlling HCC in the early stage, whereas AFP-specific T cell responses might be a signature of malignant tumour status in the advanced stage. The application of immunotherapy at an early stage of HCC development should be considered.

11.
Oxid Med Cell Longev ; 2021: 9360339, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34504644

RESUMO

Although chronic intermittent hypoxia- (IH-) induced myocardial apoptosis is an established pathophysiological process resulting in a poor prognosis for patients with obstructive sleep apnea syndrome, its underlying mechanism remains unclear. This study is aimed at exploring the role of makorin ring finger protein 1 (MKRN1) in IH-induced myocardial apoptosis and elucidating its molecular activity. First, the GSE2271 dataset was downloaded from the Gene Expression Omnibus database to identify the differentially expressed genes. Then, an SD rat model of IH, together with rat cardiomyocyte H9C2 and human cardiomyocyte AC16 IH models, was constructed. TUNEL, Western blot, and immunohistochemistry assays were used to detect cell apoptosis. Dihydroethidium staining was conducted to analyze the concentration of reactive oxygen species. In addition, RT-qPCR, Western blot, and immunohistochemistry were performed to measure the expression levels of MKRN1 and p21. The direct interaction between MKRN1 and p21 was determined using coimmunoprecipitation and ubiquitination analysis. MKRN1 expression was found to be downregulated in IH rat myocardial tissues as well as in H9C2 and AC16 cells. Upregulated expression of MKRN1 in H9C2 and AC16 cells alleviated the IH-induced reactive oxygen species production and cell apoptosis. Mechanistically, MKRN1 promoted p21 protein ubiquitination and the proteasome pathway degradation to negatively regulate p21 expression. Thus, MKRN1 regulates p21 ubiquitination to prevent IH-induced myocardial apoptosis.

13.
BMC Oral Health ; 21(1): 429, 2021 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-34482838

RESUMO

BACKGROUND: It has been widely accepted that oral health status is related to oral health literacy. The need to measure oral health literacy has led to the development of measurement instruments. This study aimed to develop a comprehensive instrument for adults and to examine its reliability and validity in China. METHODS: A three-step design process was used. First, a literature review and expert panel discussion were used to draw up a 37-item pool covering oral health knowledge, belief, practice, skill, and functional oral health literacy. The Delphi method was used to delete and modify questions in the item pool. The draft instrument was evaluated by nine experts and the consensus among them was calculated using the content validity index. The scale was then used to conduct a psychometric study among 370 participants from community health centers in Beijing. Construct validity, discriminant validity and concurrent validity were examined. The Cronbach's alpha coefficient, and test-retest methods were used to assess reliability. RESULTS: The final scale included 30 items across four dimensions. The item-level content validity index was 0.90. Exploratory factor analysis extracted four fixed factors, and the result of the Kaiser-Meyer-Olkin and Bartlett's tests was 0.752, with the model explaining 35.21% of the total variance. The four dimensions were associated with oral health knowledge, perceptions of oral health issues, oral health practice and skills, and functional oral health literacy. The mean score of the lowest 27% was significantly lower than the highest 27% (P < 0.01), suggesting adequate discriminant validity. The associations between comprehensive oral health literacy scores and educational level, income and self-reported literacy level were significant (P < 0.001), showing adequate overall concurrent validity. Internal consistency and test-retest reliability were acceptable, with a Cronbach's alpha of 0.72 and a total test-retest reliability coefficient of 0.979. CONCLUSIONS: Initial testing of the comprehensive oral health literacy instrument suggested that it is a valid and reliable instrument to evaluate individuals' oral health literacy, with four dimensions for evaluating knowledge, belief, skills, and functional oral health literacy.

14.
Int Arch Allergy Immunol ; : 1-11, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34515115

RESUMO

BACKGROUND: Few data are available concerning the prevalence and risk factors for allergic rhinitis (AR) in school children in Hubei Province which is located in the central part of China. This study investigated the epidemiological features of AR among school children in Hubei Province. METHODS: A cross-sectional questionnaire survey on AR in school children was carried out in 5 cities in Hubei Province by cluster sampling from June to September 2018. Questionnaires were filled out by children and their parents jointly. The diagnostic criteria of AR were according to the SFAR. Questions from the questionnaire were used to examine the pattern of AR. Logistic regression analysis was used to assess the risk factors for childhood allergies. RESULTS: The total prevalence rate of AR was 16.16%, with 24.31% (Wuhan), 4.34% (Xiangyang), 4.31% (Tianmen), 10.92% (Jingmen), and 11.42% (Huangshi), respectively. The prevalence of AR was positively correlated with gross domestic product per capita (p < 0.05). Multivariate analysis revealed that male, city of Wuhan, family history of allergy, food allergy, drug allergy, air purifier, exposure to dust, living in towns or urban area before 2 years old, maternal age for 26-35 years old, and frequent application of antibiotics increased the risk of AR, while daily outdoor time for 1-2 h, daily sleeping time >8 h, siblings, and breastfeeding for >6 months reduced the risk significantly. CONCLUSION: We found the apparent geographic variation of children allergies in Hubei Province. Both genetic and environment factors had impacts on the prevalence of AR in school children. Public policies should specifically target at the local risk factors for different areas.

15.
Mol Med Rep ; 24(5)2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34498711

RESUMO

The irreversible loss of cardiomyocytes is mainly the result of ischemic/reperfusion (I/R) myocardial injury, leading to persistent heart dysfunction and heart failure. It has been reported that Lycium barbarum polysaccharide (LBP) has protective effects on cardiomyocytes, but the specific mechanism is still not completely understood. The present study examined the protective role of LBP in myocardial I/R injury. Rats were subjected to myocardial I/R injury and LBP treatment. Moreover, rat myocardial H9C2 cells exposed to hypoxia/reoxygenation (H/R) were used to simulate cardiac injury during myocardial I/R process and were exposed to LBP, rapamycin (an autophagy activator) or nuclear factor­erythroid factor 2­related factor 2 (Nrf2) transfection. Morphological examination, histopathological examination and echocardiography were used to determine the cardiac injury after I/R injury. Cell viability and apoptosis were determined via MTT and flow cytometry assays, respectively. The levels of lactate dehydrogenase (LDH), creatine kinase (CK), cardiac troponin T (cTnT), IL­1ß, IL­6, TNF­α, malondialdehyde (MDA) and superoxidase dismutase (SOD) in rat serum, hearts and/or cells were assessed using ELISAs. The expression levels of Beclin 1, LC3II/LC3I, P62 and Nrf2 were analyzed via reverse transcription­quantitative PCR and western blotting. The results demonstrated that LBP improved heart function and repaired cardiomyocyte damage in I/R model rats, as well as reduced the production of cTnT, CK, LDH, IL­1ß, IL­6 and TNF­α. The in vitro study results indicated that LBP increased cell viability, the apoptosis rate, and the levels of SOD and P62, as well as reduced the levels of LDH, CK, IL­1ß, IL­6, TNF­α, MDA, Beclin 1 and LC3­II/LC3­I in H/R­injured H9C2 cells. Moreover, LBP promoted Nrf2 nuclear translocation, but decreased Nrf2 expression in the cytoplasm. Rapamycin exacerbated the aforementioned effects in H/R injured H9C2 cells, and partially reversed LBP­induced effects. Overexpressing Nrf2 counteracted I/R­induced effects and partially resisted rapamycin­induced effects. These findings demonstrated that LBP exhibited a cardiac protective effect on the ischemic myocardium of rats after reperfusion and attenuated myocardial I/R injury via autophagy inhibition­induced Nrf2 activation.

16.
J Med Internet Res ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34543228

RESUMO

BACKGROUND: The COVID-19 pandemic has raised the importance of the deployment of digital detection surveillance systems to support early warning and monitoring of infectious diseases (ID). These opportunities create a "double-edge sword" as the ethical governance of such approaches often lag behind technological achievements. OBJECTIVE: The aim was to investigate ethical issues identified from utilizing AI-augmented surveillance or early warning systems to monitor and detect common or novel ID outbreaks. METHODS: We searched relevant articles in a number of databases that addressed ethical issues of using artificial intelligence, digital surveillance systems, early warning systems and/or big data analytics technology for detecting, monitoring, or tracing ID according to PRISMA guidelines, and further identified and analysed them with a theoretical framework. RESULTS: This systematic review identified 29 articles presented in six major themes clustered under individual, organizational and societal levels, including: awareness of implementing digital surveillance, digital integrity, trust, privacy and confidentiality, civil rights, and governance. Whilst these measures were understandable during a pandemic, the public were concerned about receiving inadequate information, unclear governance frameworks, and lack of privacy protection, data integrity and autonomy when utilizing ID digital surveillance. The barriers to engagement could widen existing healthcare disparities or digital divides by underrepresenting vulnerable and at-risk populations, and expose patients' highly sensitive data such as their movements and contacts to outside sources, impinging significantly upon basic human and civil rights. CONCLUSIONS: Our findings inform ethical considerations for service delivery models for medical practitioners and policymakers implicated in the use of digital surveillance for ID spread and a basis for the global governance structure.

17.
J Exp Clin Cancer Res ; 40(1): 290, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526098

RESUMO

BACKGROUND: Accumulating evidence indicates that circRNAs may serve as essential regulators in the progression of several human cancers, but the function and mechanism of circRNAs in intrahepatic cholangiocarcinoma (ICC) are largely unknown. METHODS: RNA-seq was used to assess differentially expressed circRNAs between 4 ICC and peritumor tissues. Quantitative RT-PCR and in situ hybridization were used to determine the circHMGCS1-016 expression in ICC tissues. The function and mechanism of circHMGCS1-016 were further identified via in vivo experiments. The clinical characteristics and prognostic significance of circHMGCS1-016 were analyzed by a retrospective study. The functions of circHMGCS1-016 were assessed via modifying circRNA expression in ICC cells. Moreover, the molecular mechanisms of circHMGCS1-016 in ICC cells were explored by circRNA precipitation, miRNA immunoprecipitation, SILAC and luciferase reporter assays. RESULTS: We identified that compared with peritumor tissues, ICC tissues expressed hsa_circ_0008621 (circHMGCS1-016) high by RNA-seq, which was further identified by qRT-PCR and in situ hybridization. Moreover, the expression of circHMGCS1-016 was revealed to be associated with survival and recurrence of ICC patients. By regulating circHMGCS1-016 expression, we found that elevated circHMGCS1-016 promoted ICC development both in vitro and in vivo. By SILAC and circRNA-pull down, we demonstrated that circHMGCS1-016 induced ICC cell invasion and reshaped the tumor immune microenvironment via the miR-1236-3p/CD73 and GAL-8 axis. In ICC tissues, we uncovered that a high level of circHMGCS1-016 was positively associated with CD73 and GAL-8 expression and negatively related to the CD8+ T cells infiltration, which was further validated by establishing a humanized mouse tumor model. Importantly, we displayed that ICC patients with high levels of circHMGCS1-016 in tumor tissues benefited less from anti-PD1 treatment compared to those with low levels of circHMGCS1-016. CONCLUSIONS: CircHMGCS1-016 is a forceful contributor in ICC development and immune tolerance via miR-1236-3p/CD73 and GAL-8 axis. CircHMGCS1-016 can be explored as a new potential biomarker and therapeutic target for PD1-resistant ICC.

18.
Cell Metab ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34478633

RESUMO

Metabolic dysfunction is becoming a predominant risk for the development of many comorbidities. Ischemic heart disease (IHD) still imposes the highest disease burden among all cardiovascular diseases worldwide. However, the contributions of metabolic risk factors to IHD over time have not been fully characterized. Here, we analyzed the global disease burden of IHD and 15 associated general risk factors from 1990 to 2019 by applying the methodology framework of the Global Burden of Disease Study. We found that the global death cases due to IHD increased steadily during that time frame, while the mortality rate gradually declined. Notably, metabolic risk factors have become the leading driver of IHD, which also largely contributed to the majority of IHD-related deaths shifting from developed countries to developing countries. These findings suggest an urgent need to implement effective measures to control metabolic risk factors to prevent further increases in IHD-related deaths.

19.
J Phys Chem Lett ; : 8872-8881, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34498873

RESUMO

Designing complex cluster crystals with a specific function using simple colloidal building blocks remains a challenge in materials science. Herein, we propose a conceptually new design strategy for constructing complex cluster crystals via hierarchical self-assembly of simple soft Janus colloids. A novel and previously unreported colloidal cluster-χ (χc) phase, which resembles the essential structural features of α-manganese but at a larger length scale, is obtained through molecular dynamics simulations. The formation of the χc phase undergoes a remarkable two-step self-assembly process, that is, the self-assembly of clusters with specific size dispersity from Janus colloids, followed by the highly ordered organization of these clusters. More importantly, the dynamic exchange of particles between these clusters plays a critical role in stabilizing the χc phase. Such a conceptual design framework based on intercluster exchange has the potential to effectively construct novel complex cluster crystals by hierarchical self-assembly of colloidal building blocks.

20.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(9): 841-844, 2021 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-34487526

RESUMO

OBJECTIVE: To analyze the phenotype and genetic variant of a fetus with dysplasia of cerebellar vermis. METHODS: Gestational status and family history of the gravida was taken in combination with the imaging results of the fetus. Following elected abortion, fetal tissue and peripheral blood samples of the couple were collected for the extraction of genome DNA. Whole exome sequencing was carried out to screen potential variant associated with the phenotype of the proband. Specific PCR primers were designed to verify the results by Sanger sequencing. RESULTS: Prenatal ultrasound revealed that the fetal vermis cerebellum was poorly developed, which was similar to the previous pregnancy. Whole exome sequencing revealed that the fetus has carried compound heterozygous variants of the CPLANE1 gene, namely c.7978C>T and c.7169delT, which were respectively inherited from the husband and wife. CONCLUSION: The c.7978C>T and c.7169delT compound heterozygous variants of the CPLANE1 gene probably underlay the dysplasia of cerebellar vermis in the fetus, which has provided a basis for genetic counseling and prenatal diagnosis.


Assuntos
Anormalidades Múltiplas , Anormalidades do Olho , Doenças Renais Císticas , Anormalidades Múltiplas/genética , Cerebelo/anormalidades , Cerebelo/diagnóstico por imagem , Anormalidades do Olho/genética , Feminino , Feto , Humanos , Mutação , Fenótipo , Gravidez , Retina/anormalidades
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