Interstitial inflammation is an important mechanism of pathological damage in renal injury caused by hyperuricemia. Protease-activated receptor-2 (PAR2) is a class of targets that act upstream of the ...PI3K/AKT/NF-κB pathway and is involved in various inflammatory diseases. We induced a hyperuricemia model in rats by adenine and ethambutol gavage in an in vivo experiment. We demonstrated that PAR2 and PI3K/AKT/NF-κB pathway expression were significantly upregulated in renal tissues, with massive inflammatory cell infiltration in the renal interstitium and renal tissue injury. Treating hyperuricemic rats with AZ3451, a selective metabotropic antagonist of PAR2, we demonstrated that PAR2 antagonism inhibited the PI3K/AKT/NF-κB pathway and attenuated tubular dilation and tubulointerstitial inflammatory cell infiltration. The phospholipid metabolism profiles provided a perfect separation between the normal and hyperuricemic rats. In addition, we also found that AZ3451 can affect phospholipid metabolism. Our work suggests that PAR2 may mediate hyperuricemia-mediated renal injury by activating the PI3K/AKT/NF-κB pathway. The PAR2 antagonist AZ3451 may be a promising therapeutic strategy for hyperuricemia-induced inflammatory responses.
Purpose. An arteriovenous fistula (AVF) is the preferred vascular access mode for maintenance hemodialysis, and access stenosis and thrombosis are the primary causes of AVF dysfunction. This study is ...aimed at exploring the molecular mechanisms underlying AVF development and the roles of the heme oxygenase 1/peroxisome proliferator-activated receptor gamma (HO-1/PPAR-γ) pathway in AVF. Method. AVF model mice were established, and the vascular tissues from the arteriovenous anastomosis site were sent for mRNA sequencing. Differentially expressed mRNAs (DEmRNAs) were screened and subjected to functional analysis. Thereafter, the mice with HO-1 knockdown and coprotoporphyrin IX chloride (COPP) pretreatment were used to investigate the roles of the HO-1/PPAR-γ pathway in AVF. Results. By sequencing, 2514 DEmRNAs, including 1323 upregulated and 1191 downregulated genes, were identified. These DEmRNAs were significantly enriched in the PPAR signaling pathway, AMPK signaling pathway, glucagon signaling pathway, IL-17 signaling pathway, and Toll-like receptor signaling pathway. High expression of HO-1 and PPAR-γ reduced endothelial damage and intimal hyperplasia during AVF maturation. After AVF was established, the levels of transforming growth factor-β (TGF-β), interleukin-1β (IL-1β), interleukin-18 (IL-18), and reactive oxygen species (ROS) were significantly increased (P<0.05), and HO-1 normal expression and COPP pretreatment evidently decreased their levels in AVF (P<0.05). Additionally, AVF significantly upregulated HO-1 and PPAR-γ and downregulated MMP9, and COPP pretreatment and HO-1 normal expression further upregulated and downregulated their expression. Conclusion. The HO-1/PPAR-γ pathway may suppress intimal hyperplasia induced by AVF and protect the intima of blood vessels by regulating MMP9 and ROS, thus mitigating AVF dysfunction.
RNA, like DNA and proteins, has been discovered to undergo dynamic and reversible chemical alterations, increasing the diversity and functional complexity of the molecule. N-6-methyladenosine (m
6
A) ...RNA methylation serves as a bridge between transcription and translation and is critical for many diseases’ progression. There is a complex interrelationship between m
6
A modifications and other epigenetic modifications. Their crosstalk significantly affects transcriptional outputs, translation, recruitment of chromatin modifiers, as well as the deployment of the m
6
A methyltransferase complex at target sites. This article outlines the potential function of m
6
A RNA methylation in epigenetics and summarizes its interactions with histone modifications.
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•A sensitive electrochemiluminescence biosensor for miRNA-21 had been proposed.•Homogeneous strategy reduced the steric hindrance from the electrode surface.•Hybridization chain ...reaction amplification had been applied to improve the sensitivity.•Separation and enrichment of magnetic beads reduced the background signal and enhanced the sensitivity.
MicroRNA-21(miRNA-21) can act as a novel biomarker in early stage of acute kidney injury (AKI). The development of simple but sensitive miRNA-21 detection technology is helpful for prevention and treatment of AKI. In this work, based on the cascaded signal amplifications of the target-induced hybridization chain reaction (HCR) and magnetic assisted enrichment, a highly sensitive homogeneous electrochemiluminescence (ECL) biosensor for miRNA-21 detection had been developed. Firstly, capture probe H1 (CPH1) had been modified on magnetic beads (MBs) which could capture target (miRNA-21) and trigger HCR amplification to produce long strand dsDNA in the homogeneous solution. Ru(phen)32+ could be embedded into the grooves of dsDNA and played the role of luminous tag, which could be separated by magnetic easily to realize the enrichment. Then the enriched products had been dissolved in the buffer solution and the ECL signal could be detected easily. The ECL intensity had a linear correlation with the logarithm of miRNA-21 concentration in the range of 1.0 fM-1.0 nM, the detection limit was 0.14 fM. The method developed in this work showed well sensitivity, specificity, which had been applied to detect miRNA-21 in urine of AKI patients with satisfied results.
The great selectivity and trans-cleavage activity of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas13a had been coupled with high amplification efficiency of hybridization ...chain reaction (HCR) and magnetic-assisted enrichment, high sensitivity of electrochemiluminescence (ECL) detection to develop an ultra-sensitive biosensor for microRNA-21 (miRNA-21). The CRISPR/Cas13a was used to recognize target RNA with high specificity and performed the trans-cleavage activity. An initiation strand was generated to bind to the probe on the surface of nanomagnetic beads and then trigged HCR to produce long double-strand DNAs (dsDNAs) to realize signal amplification. Ru(phen)
3
2+
can be inserted in the groove of the dsDNAs and acts as the ECL indicator, which can be separated through magnetic enrichment and allowed the platform to reduce the signal background. Under the optimized conditions, there is a good linear correlation between the ECL intensity and the logarithm of miRNA-21 concentration in the range 1 fM–10 nM; the limit of detection (LOD) was 0.53 fM. The proposed system was applied to detect miRNA-21 from the urine of acute kidney injury (AKI) patients with good results.
Graphical Abstract
Observing the effects of high-volume hemofiltration (HVHF) treatment on the monocytes apoptosis, antigen presentation, and secretion function, this study investigated the mechanism of HVHF effect on ...immunity homeostasis in multiple organ dysfunction syndrome (MODS) in an animal model.
Lipopolysaccharides were administered in 12 Beagle dogs in order to induce MODS. Six dogs were randomly assigned to receive HVHF treatment for 12 hours (HVHF group) and the rest did not receive any treatment (the MODS group). The expression of DLA-DR, apoptosis, and cytokine levels were measured at 7 time points: normal condition (T1), after operation (T2), and zero, 3, 6, 9, and 12 hours after endotoxin injection (T3 to T7, respectively).
Apoptosis of CD14+ mononuclear cell increased in early and late stages gradually in the MODS group and began to decline gradually after the HVHF treatment. There was a significant difference between the two groups at time points T2 to T7 (P < .01). After HVHF, the impaired expression of dog leukocyte antigen-DR showed an improvement trend in the HVHF group, which was significant better at T5 and T7 than that in the MODS group (P < .05). Interleukin-4 secretion increased significantly with HVHF and was significantly higher at time points T4 to T7 as compared with the MODS group (P < .01). Conclusions. High-volume hemofiltration can alleviate the mononuclear cell apoptosis, improve antigen-presenting function and secretion function, inhibit the release of inflammatory factors, and maintain immune homeostasis, and consequently alleviate symptoms of MODS effectively.
Cerebral autoregulation is the intrinsic ability of the brain to maintain adequate cerebral perfusion in the presence of blood pressure changes. A large number of methods to assess the quality of ...cerebral autoregulation have been proposed over the last 30 years. However, no single method has been universally accepted as a gold standard. Therefore, the choice of which method to employ to quantify cerebral autoregulation remains a matter of personal choice. Nevertheless, given the concept that cerebral autoregulation represents the dynamic relationship between blood pressure (stimulus or input) and cerebral blood flow (response or output), transfer function analysis became the most popular approach adopted in studies based on spontaneous fluctuations of blood pressure. Despite its sound theoretical background, the literature shows considerable variation in implementation of transfer function analysis in practice, which has limited comparisons between studies and hindered progress towards clinical application. Therefore, the purpose of the present white paper is to improve standardisation of parameters and settings adopted for application of transfer function analysis in studies of dynamic cerebral autoregulation. The development of these recommendations was initiated by (but not confined to) the Cerebral Autoregulation Research Network (CARNet – www.car-net.org).
Abstract Objective To compare the prevalence, the clinical manifestations, familial aggregation and heritability of Kashin–Beck disease (KBD) and Sayiwak disease (SD) in China. Methods 10,823 people ...from 1361 families in 14 villages in Linyou County, Shaanxi Province, were examined for KBD, and 2264 people from 552 families in Sayiwak village, Kashi city, Xinjiang, were examined for SD. The investigation included documentation of individual information and clinical manifestations. Patients were subject to radiographic imaging of the right hand. t -Tests and chi-square tests were used to examine correlations of the diseases with age and gender in each of the two groups. Analysis of familial aggregation was conducted with the chi-square distribution analysis of goodness of fit using the SAS8.0 program. The Li–Mantel–Gart method was employed for the segregation analysis. The Falconer regression method11 was employed to estimate heritability ( h2 ). Results The prevalence of KBD in Linyou County was 10.90%, and of SD in Sayiwak village was 0.57%. Of the 21 clinical signs examined, KBD cases exhibited 19 signs (90.48%) and SD cases exhibited 18 signs (85.71%), which indicate similarities between the two diseases. However, different clinical signs were evident between the KBD and SD cases, with different impairment rates among joints of limbs in KBD and similar rates in SD. A comparison of radiological features of limb arthropathy between the two diseases showed differences in several characteristics between the two diseases. In addition, measurements of stature and sitting height showed significant differences in bone development between the two diseases. For KBD cases, the values of h2 in the first-degree and the second-degree relatives were 41.76% and 37.20% ( P < 0.05). The CI of h2 was 31.17–52.38 and 19.86–54.55, with a segregation ratio of P = 0.12, SE( P ) = 0.014, 95%CI 0.09–0.15, less than 0.25( χ2 = 42.36, df = 1, P < 0.001). For SD cases, the values of h2 were 155.61%, 273.63% and 236.83%. The 95% CIs of h2 were 133.20–178.12, 229.83–317.42 and 145.83–327.81, respectively, with a segregation ratio of P = 0.34, SE( P ) = 0.059, and CIs between 0.22 and 0.45( χ2 = 4.9817, df = 1, P > 0.05). Conclusion The results indicate both similarities and differences in the clinical manifestations of KBD and SD. However, environmental factors appear to play a major role in KBD, while hereditability is a major factor in SD.
•Population and income in China and US have influence on CO2 change.•Sectors CO2 emission has impact on human development index, economic growth, Health Life Expectancy (HLE).•Sector CO2 emissions ...are predicted to increase by 2030 in most of the countries.•Health Life Expectancy showed strong relationship with sector CO2 emissions.
This study explored the drivers of carbon dioxide (CO2) emission (million metric tons) in the top 10 emitting countries (China, United States, India, Russian Federation, Japan, Germany, South Korea, Iran, Canada, and Saudi Arabia). The logarithmic mean Divisia index (LMDI) method was used to analyse the drive of CO2 emission change pertinent to population (thousand people), per capita income, energy intensity (metric ton energy/$GDP) and carbon intensity effects (metric ton CO2/ton energy) from 1991 to 2014. Further, analysis was carried out for the impact of CO2 emitted by different sectors (Agriculture, Energy, Fugitive, Industrial, Manufacturing, Transportation and Waste), the corresponding Human Development Index (HDI) and economic growth (EG%) using the panel model. This was done along with predictions for the total CO2 emissions over the next 16 years. The general results showed that the CO2 emission change has a significant effect by population and income, especially in China and the United states. Also, there is a strong relationship between human development index, economic growth, as well as Healthy Life Expectancy (HLE) with sector CO2 emission for most of the investigated countries. The forecast of sectors CO2 emission for the year 2030, showed an increase of CO2 for all the countries, which requires a policy plan aimed at decreasing their CO2 emission for a safer environment.
Thyroid nodules are very common all over the world, and China is no exception. Ultrasound plays an important role in determining the risk stratification of thyroid nodules, which is critical for ...clinical management of thyroid nodules. For the past few years, many versions of TIRADS (Thyroid Imaging Reporting and Data System) have been put forward by several institutions with the aim to identify whether nodules require fine-needle biopsy or ultrasound follow-up. However, no version of TIRADS has been widely adopted worldwide till date. In China, as many as ten versions of TIRADS have been used in different hospitals nationwide, causing a lot of confusion. With the support of the Superficial Organ and Vascular Ultrasound Group of the Society of Ultrasound in Medicine of the Chinese Medical Association, the Chinese-TIRADS that is in line with China’s national conditions and medical status was established based on literature review, expert consensus, and multicenter data provided by the Chinese Artificial Intelligence Alliance for Thyroid and Breast Ultrasound.
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