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1.
Neurochem Res ; 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34665391

RESUMO

Subarachnoid hemorrhage (SAH), as one of the most severe hemorrhagic strokes, is closely related to neuronal damage. Neurogenesis is a promising therapy, however, reliable targets are currently lacking. Increasing evidence has indicated that CD24 is associated with the growth of hippocampal neurons and the regulation of neural stem/precursor cell proliferation. To investigate the potential effect of CD24 in astrocytes on neuron growth in the hippocampus, we used a Transwell co-culture system of hippocampal astrocytes and neurons, and oxyhemoglobin (OxyHb) was added to the culture medium to mimic SAH in vitro. A specific lentivirus was used to knock down CD24 expression in astrocytes, which was verified by western blot, quantitative real-time polymerase chain reaction, and immunofluorescent staining. Astrocyte activation, neurite elongation, neuronal apoptosis, and cell viability were also assessed. We first determined the augmented expression level of CD24 in hippocampal astrocytes after SAH. A similar result was observed in cultured astrocytes exposed to OxyHb, and a corresponding change in SHP2/ERK was also noticed. CD24 in astrocytes was then downregulated by the lentivirus, which led to the impairment of axons and dendrites on the co-cultured neurons. Aggravated neuronal apoptosis was induced by the CD24 downregulation in astrocytes, which might be a result of a lower level of brain derived neurotrophic factor (BDNF). In conclusion, the knock-down of CD24 in astrocytes suppressed hippocampal neuron growth, in which the SHP2-ERK signaling pathway and BNDF were possibly involved.

2.
Nanomaterials (Basel) ; 11(10)2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34685119

RESUMO

Recent investigations of fundamental electronic properties (especially the carrier transport mechanisms) of Si nanocrystal embedded in the amorphous SiC films are highly desired in order to further develop their applications in nano-electronic and optoelectronic devices. Here, Boron-doped Si nanocrystals embedded in the amorphous SiC films were prepared by thermal annealing of Boron-doped amorphous Si-rich SiC films with various Si/C ratios. Carrier transport properties in combination with microstructural characteristics were investigated via temperature dependence Hall effect measurements. It should be pointed out that Hall mobilities, carrier concentrations as well as conductivities in films were increased with Si/C ratio, which could be reached to the maximum of 7.2 cm2/V∙s, 4.6 × 1019 cm-3 and 87.5 S∙cm-1, respectively. Notably, different kinds of carrier transport behaviors, such as Mott variable-range hopping, multiple phonon hopping, percolation hopping and thermally activation conduction that play an important role in the transport process, were identified within different temperature ranges (10 K~400 K) in the films of different Si/C ratio. The changes from Mott variable-range hopping process to thermally activation conduction process with temperature were observed and discussed in detail.

3.
Clin Chim Acta ; 523: 267-272, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34653385

RESUMO

BACKGROUND AND AIMS: Hyperphenylalaninemia (HPA) is a common autosomal recessive disorder of phenylalanine metabolism, mainly caused by the deficiency of phenylalanine hydroxylase gene (PAH). A simple, fast, and accurate assay to achieve early diagnosis for children with HPA is required. MATERIALS AND METHODS: In the present study, we established a SNaPshot-based assay that allows the simultaneous genotyping of 96 hotspot variants in the PAH gene. First, 18 Chinese HPA patients were analyzed by next generation sequencing (NGS) and SNaPshot in parallel. Then, the SNaPshot assay was performed to analyze the mutational spectrum of the PAH in 4,276 individuals in Eastern China. RESULTS: A total of 36 variants in the PAH gene were successfully identified by NGS, while the SNaPshot assay identified 34 PAH variants in these patients. Thus, the SNaPshot assay achieved the sensitivity and specificity of 91.6% and 100.0%, respectively. Furthermore, the carrier rate was approximately 1 in 58 (1.73%) in 4,276 individuals, and c.728G > A was the most common variant. CONCLUSION: In summary, SNaPshot can accurately and rapidly detect PAH gene variants at a comparable performance and lower cost as compared with NGS. Our results suggest that SNaPshot may serve as a promising approach for a routine genetic test in clinical practice.

4.
Appl Opt ; 60(26): 8057-8068, 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34613068

RESUMO

As a common tracer in the atmosphere, airglow can be used as an important means to study the interaction between the lower atmosphere, near space, and ionosphere. In the near-Earth space, the high-altitude balloon can realize long time flight, which makes the airglow detection realize both high range resolution and time resolution. In this paper, a balloon-based multi-band airglow imager is designed, which can observe OI (557.7 nm), Na (589.3 nm), OI (630.0 nm), and OH (720-910 nm) with annular field of view (30° inner ring and 80° outer ring), and its resolution is 500 m at 250 km. The multi-band airglow imager designed in this paper is equipped in the payload cabin and raised to above 30 km for flat flying for more than 6 h. The experimental results show that the imager worked normally, and airglow images were photographed and stored; the optical system can stand the harsh environment in the near space. The multi-band airglow imager designed in this paper will take part in other near-space exploration tasks in the future and obtain corresponding results.

5.
Nat Nanotechnol ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34504324

RESUMO

Two-dimensional materials are promising candidates for future electronics due to unmatched device performance at atomic limit and low-temperature heterogeneous integration. To adopt these emerging materials in computing and optoelectronic systems, back end of line (BEOL) integration with mainstream technologies is needed. Here, we show the integration of large-area MoS2 thin-film transistors (TFTs) with nitride micro light-emitting diodes (LEDs) through a BEOL process and demonstrate high-resolution displays. The MoS2 transistors exhibit median mobility of 54 cm2 V-1s -1, 210 µA µm-1 drive current and excellent uniformity. The TFTs can drive micrometre-sized LEDs to 7.1 × 107 cd m-2 luminance under low voltage. Comprehensive analysis on driving capability, response time, power consumption and modulation scheme indicates that MoS2 TFTs are suitable for a range of display applications up to the high resolution and brightness limit. We further demonstrate prototypical 32 × 32 active-matrix displays at 1,270 pixels-per-inch resolution. Moreover, our process is fully monolithic, low-temperature, scalable and compatible with microelectronic processing.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34498942

RESUMO

AIMS: Metabolic disorders may play key roles in oxidative stress and neuronal apoptosis in response to early brain injury (EBI) after subarachnoid hemorrhage (SAH). Pyruvate dehydrogenase (PDH) is related to oxidative stress in EBI, and its activity obviously decreases after SAH. We discovered that only pyruvate dehydrogenase kinase 4 (PDK4) expression was obviously increased among the four PDK isozymes after SAH in preliminary experiments. Therefore, we attempted to investigate the effects and corresponding mechanisms of PDK4 on oxidative stress after SAH. RESULTS: First, we confirmed that PDK4 overexpression promoted PDH phosphorylation, inhibited PDH activity and changed cell metabolism after SAH. An siRNA targeting PDK4, a lentiviral PDK4 overexpression vector and dichloroacetic acid (DCA) were used to regulate the expression and activity of PDK4. The siRNA decreased PDH phosphorylation, promoted reactive oxygen species (ROS) production, activated the apoptosis signal-regulating kinase 1 (ASK1)/p38 pathway and induced neuronal apoptosis. The lentivirus further attenuated PDH activity, oxidative stress and neuronal apoptosis. DCA inhibited the activity of PDK4 but increased the expression of PDK4 due to a feedback mechanism. Inactivated PDK4 did not effectively suppress PDH activity, which increased ROS production, activated the ASK1/p38 pathway and led to neuronal apoptosis. INNOVATION: This study provides new insights into the potential antioxidant and antiapoptotic effects of the PDK4-PDH axis on EBI after SAH. CONCLUSIONS: The early overexpression of PDK4 after SAH may attenuate neuronal apoptosis by reducing oxidative stress via the ROS/ASK1/p38 pathway. PDK4 may be a new potential therapeutic target to ameliorate EBI after SAH.

7.
Front Bioeng Biotechnol ; 9: 756758, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568306

RESUMO

Based on the phase separation phenomenon in micro-droplets, polymer-lipid Janus particles were prepared on a microfluidic flow focusing chip. Phase separation of droplets was caused by solvent volatilization and Janus morphology was formed under the action of interfacial tension. Because phase change from solid to liquid of the lipid hemisphere could be triggered by physiological temperature, the lipid hemisphere could be used for rapid release of drugs. While the polymer we selected was pH sensitive that the polymer hemisphere could degrade under acidic conditions, making it possible to release drugs in a specific pH environment, such as tumor tissues. Janus particles with different structures were obtained by changing the experimental conditions. To widen the application range of the particles, fatty alcohol and fatty acid-based phase change materials were also employed to prepare the particles, such as 1-tetradecanol, 1-hexadecanol and lauric acid. The melting points of these substances are higher than the physiological temperature, which can be applied in fever triggered drug release or in thermotherapy. The introduction of poly (lactic-co-glycolic acid) enabled the formation of multicompartment particles with three distinct materials. With different degradation properties of each compartment, the particles generated in this work may find applications in programmed and sequential drug release triggered by multiple stimuli.

8.
Parasit Vectors ; 14(1): 498, 2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34565443

RESUMO

BACKGROUND: Trichinella spiralis (T. spiralis) is a parasite occurring worldwide that has been proven to have antitumour ability. However, studies on the antitumour effects of cross antigens between the tumour and T. spiralis or antibodies against cross antigens between tumours and T. spiralis are rare. METHODS: To study the role of cross antigens between osteosarcoma and T. spiralis, we first screened the cDNA expression library of T. spiralis muscle larvae to obtain the cross antigen gene tumour protein D52 (TPD52), and prepared fusion protein TPD52 and its antiserum. The anti-osteosarcoma effect of the anti-TPD52 antiserum was studied using cell proliferation and cytotoxicity assays as well as in vivo animal models; preliminary data on the mechanism were obtained using western blot and immunohistochemistry analyses. RESULTS: Our results indicated that TPD52 was mainly localized in the cytoplasm of MG-63 cells. Anti-TPD52 antiserum inhibited the proliferation of MG-63 cells and the growth of osteosarcoma in a dose-dependent manner. The tumour inhibition rate in the 100 µg treatment group was 61.95%. Enzyme-linked immunosorbent assay showed that injection of anti-TPD52 antiserum increased the serum levels of IFN-γ, TNF-α, and IL-12 in nude mice. Haematoxylin and eosin staining showed that anti-TPD52 antiserum did not cause significant pathological damage. Apoptosis of osteosarcoma cells was induced by anti-TPD52 antiserum in vivo and in vitro. CONCLUSIONS: Anti-TPD52 antiserum exerts an anti-osteosarcoma effect by inducing apoptosis without causing histopathological damage.

9.
Signal Transduct Target Ther ; 6(1): 329, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34471087

RESUMO

It's a challenge for detecting the therapeutic targets of a polypharmacological drug from variations in the responsed networks in the differentiated populations with complex diseases, as stable coronary heart disease. Here, in an adaptive, 31-center, randomized, double-blind trial involving 920 patients with moderate symptomatic stable angina treated by 14-day Danhong injection(DHI), a kind of polypharmacological drug with high quality control, or placebo (0.9% saline), with 76-day following-up, we firstly confirmed that DHI could increase the proportion of patients with clinically significant changes on angina-frequency assessed by Seattle Angina Questionnaire (ΔSAQ-AF ≥ 20) (12.78% at Day 30, 95% confidence interval [CI] 5.86-19.71%, P = 0.0003, 13.82% at Day 60, 95% CI 6.82-20.82%, P = 0.0001 and 8.95% at Day 90, 95% CI 2.06-15.85%, P = 0.01). We also found that there were no significant differences in new-onset major vascular events (P = 0.8502) and serious adverse events (P = 0.9105) between DHI and placebo. After performing the RNA sequencing in 62 selected patients, we developed a systemic modular approach to identify differentially expressed modules (DEMs) of DHI with the Zsummary value less than 0 compared with the control group, calculated by weighted gene co-expression network analysis (WGCNA), and sketched out the basic framework on a modular map with 25 functional modules targeted by DHI. Furthermore, the effective therapeutic module (ETM), defined as the highest correlation value with the phenotype alteration (ΔSAQ-AF, the change in SAQ-AF at Day 30 from baseline) calculated by WGCNA, was identified in the population with the best effect (ΔSAQ-AF ≥ 40), which is related to anticoagulation and regulation of cholesterol metabolism. We assessed the modular flexibility of this ETM using the global topological D value based on Euclidean distance, which is correlated with phenotype alteration (r2: 0.8204, P = 0.019) by linear regression. Our study identified the anti-angina therapeutic module in the effective population treated by the multi-target drug. Modular methods facilitate the discovery of network pharmacological mechanisms and the advancement of precision medicine. (ClinicalTrials.gov identifier: NCT01681316).

10.
Nutrients ; 13(9)2021 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-34578814

RESUMO

Dietary counselling has been identified as one of the nutritional strategies to alleviate cardiometabolic health conditions. Its effectiveness however may vary due to factors such as intensity level and provider while this has not been comprehensively studied. This systematic review and meta-analysis aimed to assess the effects of dietary counselling on the cardiometabolic health in middle-aged and older adults and the sub-group analyses with dietary counselling intensity and the provider were also assessed. Four databases including PubMed, CINAHL Plus with Full Text, Cochrane Library and EMBASE were systematically searched. Data from 22 randomised controlled trials (RCTs) were compiled and those from 9 RCTs were utilised for meta-analysis. Dietary counselling lowered total cholesterol (TC) and fasting blood sugar (FBS) but had no impact on triglycerides (TG) and low-density lipoprotein (LDL). Sub-group analysis revealed significant lowering effect of high intensity dietary counselling for TG (weighted mean difference (WMD): -0.24 mmol/L, 95% confidence intervals (CIs): -0.40 to -0.09), TC (WMD: -0.31 mmol/L, 95% CIs: -0.49 to -0.13), LDL (WMD: -0.39 mmol/L, 95% CIs: -0.61 to -0.16) and FBS (WMD: -0.69 mmol/L, 95% CIs: -0.99 to -0.40) while medium or low intensity dietary counselling did not show favouring effects. Counselling provider showed differential responses on cardiometabolic health between dietitian and all other groups. The findings from this systematic review and meta-analysis suggest that dietary counselling is a beneficial dietary strategy to improve cardiometabolic health in middle-aged and older adults with the emphasis on the counselling intensity.

11.
Spectrochim Acta A Mol Biomol Spectrosc ; 265: 120359, 2021 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-34530202

RESUMO

Owing to the attractive biological and pharmacological activities, sensitive and selective detection of curcumin is of great significance. Nanomaterials possessing unique optical properties exhibit potential applications in the fluorescent detection of curcumin. This review first discussed the detection strategies of fluorescent nanosensors. In the subsequent section, we highlighted the recent advances of different nanomaterials for fluorescent detection of curcumin, including semiconductor QDs, lanthanide upconversion nanoparticles, fluorescent metal nanoclusters, and carbon quantum dots. And we further provided the merits of fluorescent nanosensors for curcumin. Lastly, the challenges and further directions were presented.

12.
Cell Death Dis ; 12(10): 866, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556635

RESUMO

Tubules injury and immune cell activation are the common pathogenic mechanisms in acute kidney injury (AKI). However, the exact modes of immune cell activation following tubule damage are not fully understood. Here we uncovered that the release of cytoplasmic spliceosome associated protein 130 (SAP130) from the damaged tubular cells mediated necroinflammation by triggering macrophage activation via miRNA-219c(miR-219c)/Mincle-dependent mechanism in unilateral ureteral obstruction (UUO) and cisplatin-induced AKI mouse models, and in patients with acute tubule necrosis (ATN). In the AKI kidneys, we found that Mincle expression was tightly correlated to the necrotic tubular epithelial cells (TECs) with higher expression of SAP130, a damaged associated molecule pattern (DAMP), suggesting that SAP130 released from damaged tubular cells may trigger macrophage activation and necroinflammation. This was confirmed in vivo in which administration of SAP130-rich supernatant from dead TECs or recombinant SAP130 promoted Mincle expression and macrophage accumulation which became worsen with profound tubulointerstitial inflammation in LPS-primed Mincle WT mice but not in Mincle deficient mice. Further studies identified that Mincle was negatively regulated via miR-219c-3p in macrophages as miR-219c-3p bound Mincle 3'-UTR to inhibit Mincle translation. Besides, lentivirus-mediated renal miR-219c-3p overexpression blunted Mincle and proinflammatory cytokine expression as well as macrophage infiltration in the inflamed kidney of UUO mice. In conclusion, SAP130 is released by damaged tubules which elicit Mincle activation on macrophages and renal necroinflammation via the miR-219c-3p-dependent mechanism. Results from this study suggest that targeting miR-219c-3p/Mincle signaling may represent a novel therapy for AKI.

13.
J Transl Med ; 19(1): 379, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34488791

RESUMO

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


Assuntos
Neoplasias Colorretais , Fatores Reguladores de Interferon , Biomarcadores Tumorais , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Fatores Reguladores de Interferon/genética , Prognóstico , Microambiente Tumoral
14.
Appl Environ Microbiol ; : AEM0106521, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34524897

RESUMO

Recent omics studies have provided invaluable insights into the metabolic potential, adaptation and evolution of novel archaeal lineages from a variety of extreme environments. We have utilized a genome-resolved metagenomic approach to recover eight medium- to high-quality metagenome-assembled genomes (MAGs) that likely represent a new order ("Candidatus Sysuiplasmatales") within Thermoplasmata from mine tailings and acid mine drainage (AMD) sediments sampled from two copper mines in South China. 16S rRNA gene based analyses revealed a narrow habitat range for these uncultured archaea limiting to AMD and hot spring-related environments. Metabolic reconstruction indicated a facultatively anaerobic heterotrophic lifestyle. This may allow the archaea to adapt to oxygen fluctuations and is thus in marked contrast to the majority of lineages in the domain Archaea which typically show obligately anaerobic metabolisms. Notably, "Ca. Sysuiplasmatales" could conserve energy through degradation of fatty acids, amino acid metabolism and oxidation of reduced inorganic sulfur compounds (RISCs), suggesting that they may contribute to acid generation in the extreme mine environments. Unlike its closely related Methanomassiliicoccales and "Ca. Gimiplasmatales", "Ca. Sysuiplasmatales" lack the capacity to perform methanogenesis and carbon fixation. Ancestral state reconstruction indicated that "Ca. Sysuiplasmatales" and its closely related Methanomassiliicoccales, "Ca. Gimiplasmatales", and the SG8-5 and the RBG-16-68-12 orders originated from a facultatively anaerobic ancestor capable of carbon fixation via the bacterial-type H4F Wood-Ljungdahl pathway (WLP). Their metabolic divergence might be attributed to different evolutionary paths. Importance A wide array of archaea populate Earth's extreme environments thereby they may play important roles in mediating biogeochemical processes such as iron and sulfur cycling. However, our knowledge of archaeal biology and evolution is still limited considering the uncultured majority of archaeal diversity. For instance, most order-level lineages except Thermoplasmatales, Aciduliprofundales and Methanomassiliicoccales within Thermoplasmata do not have cultured representatives. Here, we report the discovery and genomic characterization of a novel order, namely "Ca. Sysuiplasmatales", within Thermoplasmata in the extremely acidic mine environments. "Ca. Sysuiplasmatales" are inferred to be facultatively anaerobic heterotrophs and likely contribute to acid generation through the oxidation of RISCs. The physiological divergence between "Ca. Sysuiplasmatales" and its closely related Thermoplasmata lineages may be attributed to different evolutionary paths. These results expand our knowledge of archaea in the extreme mine ecosystem.

15.
J Genet Genomics ; 48(6): 452-462, 2021 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-34353741

RESUMO

Airway smooth muscle (ASM) has developed a mechanical adaption mechanism by which it transduces force and responds to environmental forces, which is essential for periodic breathing. Cytoskeletal reorganization has been implicated in this process, but the regulatory mechanism remains to be determined. We here observe that ASM abundantly expresses cytoskeleton regulators Limk1 and Limk2, and their expression levels are further upregulated in chronic obstructive pulmonary disease (COPD) animals. By establishing mouse lines with deletions of Limk1 or Limk2, we analyse the length-sensitive contraction, F/G-actin dynamics, and F-actin pool of mutant ASM cells. As LIMK1 phosphorylation does not respond to the contractile stimulation, LIMK1-deficient ASM develops normal maximal force, while LIMK2 or LIMK1/LIMK2 deficient ASMs show approximately 30% inhibition. LIMK2 deletion causes a significant decrease in cofilin phosphorylation along with a reduced F/G-actin ratio. As LIMK2 functions independently of cross-bridge movement, this observation indicates that LIMK2 is necessary for F-actin dynamics and hence force transduction. Moreover, LIMK2-deficient ASMs display abolishes stretching-induced suppression of 5-hydroxytryptamine (5-HT) but not acetylcholine-evoks force, which is due to the differential contraction mechanisms adopted by the agonists. We propose that LIMK2-mediated cofilin phosphorylation is required for membrane cytoskeleton reorganization that is necessary for ASM mechanical adaption including the 5-HT-evoked length-sensitive effect.

16.
Sci Rep ; 11(1): 17111, 2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34429489

RESUMO

Interferon-gamma (IFN-γ) is a cytokine involved in the pathogenesis of Takayasu's arteritis (TAK). However, the source of IFN-γ in TAK patients is not fully clear. We aimed to investigate the source of IFN-γ in TAK. 60 TAK patients and 35 health controls were enrolled. The lymphocyte subsets of peripheral blood were detected by flow cytometry, cytokines were detected by Bio-plex. The correlation among lymphocyte subsets, cytokines and disease activity indexes was analyzed by person correlation. The level of serum IFN-γ in TAK patients was significantly increased (P < 0.05). The percentage of CD3+IFN-γ+ cells in peripheral blood CD3+ cells was significantly higher in TAK patients than that of healthy control group (P = 0.002). A higher proportion of CD3+CD8+IFN-γ+ cells/CD3+IFN-γ+ cells (40.23 ± 11.98% vs 35.12 ± 11.51%, P = 0.049), and a significantly lower CD3+CD4+IFN-γ+/ CD3+CD8+IFN-γ+ ratio (1.34 ± 0.62% vs 1.80 ± 1.33%, P = 0.027) were showed in the TAK group than that of control group. The CD3+CD8+IFN-γ+/CD3+IFN-γ+ ratio was positively correlated with CD3+IFN-γ+cells/ CD3+cells ratio (r = 0.430, P = 0.001), serum IFN-γ level (r = 0.318, P = 0.040) and IL-17 level (r = 0.326, P = 0.031). It was negatively correlated with CD3+CD4+IFN-γ+/CD3+IFN-γ+ ratio (r = - 0.845, P < 0.001). IFN-γ secreted by CD3+CD8 + T cells is an important source of serum IFN-γ in TAK patients.

17.
Diabetes ; 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376476

RESUMO

Foot process effacement is an important feature of early diabetic nephropathy (DN) which is closely related to the development of albuminuria. Under certain nephrotic conditions, the integrity and function of the glomerular slit diaphragm (SD) structure were impaired and replaced by the tight junction (TJ) structure, resulting in so-called SD-TJ transition, which could partially explain the effacement of foot processes at the molecular level. However, the mechanism underlying the SD-TJ transition has not been described in DN. Here, we demonstrated that impaired autophagic flux blocked p62 mediated degradation of ZO-1 (TJ protein) and promoted podocytes injury via activation of caspase 3 and caspase 8. Interestingly, the expression of VDR in podocytes was decreased under diabetic condition which impaired autophagic flux through down-regulating Atg3. Of note, we also found that VDR abundance was negatively associated with impaired autophagic flux and SD-TJ transition in the glomeruli from human renal biopsy samples with DN. Furthermore, VDR activation improved autophagic flux and attenuated SD-TJ transition in the glomeruli of diabetic animal models. In conclusion, our data provided the novel insight that VDR/Atg3 axis deficiency resulted in SD-TJ transition and foot processes effacement via blocking p62-mediated autophagy pathway in DN.

18.
Front Public Health ; 9: 710896, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34381753

RESUMO

This paper explores the impact of medical insurance on the possibility of household participation in the stock market and the portfolio share of equity, applying Probit, and Tobit models with the data from China Household Finance Survey (CHFS). The empirical results highlight that participating in medical insurance can significantly increase the possibility of households participating in the stock market and the portfolio share of equity, and have passed the robustness tests, including propensity score matching (PSM), altering estimation methods, replacing explained variables, and eliminating samples. Besides, heterogeneity analysis shows that the impact of medical insurance on household stock market participation is more significant in eastern region, urban areas, and households with higher income level. Further mechanism analysis implies that household participation in medical insurance mainly affects their stock market participation through preventive savings effect. It is necessary to improve the medical insurance system and encourage household participation in stock market so as to further promote financial development in China.


Assuntos
Características da Família , Seguro Saúde , China , Humanos , Renda , Inquéritos e Questionários
19.
J Transl Med ; 19(1): 347, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34389031

RESUMO

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


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Linhagem Celular Tumoral , Humanos , Ferro , Camundongos , Macrófagos Associados a Tumor
20.
J Transl Med ; 19(1): 355, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404433

RESUMO

BACKGROUND: Diabetic nephropathy (DN) is a leading cause of renal failure, whereas the effective and early diagnostic biomarkers are still lacking. METHODS: Fourteen cytokines and chemokines mRNA were detected in urinary extracellular vesicles (EVs) from the screening cohort including 4 healthy controls (HC), 4 diabetes mellitus (DM) and 4 biopsy-proven DN patients, and was validated in another 16 HC and 15 DM and 28 DN patients. Correlation analysis was performed between the candidate biomarkers and clinic parameters as well as kidney histological changes. The findings were also confirmed in DN rat model with single injection of STZ. RESULTS: The number of small EVs secreted in urine was increased in DN patients compared to DM patients and healthy controls, with expression of AQP1 (a marker of proximal tubules) and AQP2 (a marker of distal/collecting tubules). Small EVs derived CCL21 mRNA increased significantly in DN patients and correlated with level of proteinuria and eGFR. Interestingly, elevated CCL21 mRNA from urine small EVs was observed in DN patients with normal renal function and could discriminate early DN patients from DM more efficiently compared to eGFR and proteinuria. CCL21 also showed an accurate diagnostic ability in distinguishing incipient from overt DN. Histologically, CCL21 mRNA expression increased progressively with the deterioration of tubulointerstitial inflammation and showed the highest level in nodular sclerosis group (class III) in DN patients. Remarkable infiltration of CD3 positive T cells including both CD4 and CD8 positive T cell population were observed in DN patients with high-CCL21 expression. Besides, accumulation of CD3 positive T cells correlated with level of urinary small EVs derived CCL21 and co-localized with CCL21 in the tubulointerstitium in DN patients. Finally, the correlation of CCL21 expression in renal cortex and urinary small EVs was confirmed in STZ-induced DN rat model. CONCLUSIONS: Urinary small EVs derived CCL21 mRNA may serve as early biomarker for identifying DN linked with pathogenesis. CCL21 mRNA mediated T cell infiltration may constitute the key mechanism of chronic inflammation in DN.


Assuntos
Quimiocina CCL21 , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Vesículas Extracelulares , Animais , Aquaporina 2 , Biomarcadores , Quimiocina CCL21/genética , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/genética , Humanos , RNA Mensageiro/genética , Ratos
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