Chronic kidney disease (CKD) is a progressive damage of kidneys that can no longer serve the blood-filtering function, and is a life-threatening condition. Skeletal muscle wasting is a common ...complication of CKD. Yet the relationship between kidney and skeletal muscle in CKD remains unclear. Exosomes, a type of small membrane-bound vesicles released from cells to the extracellular environment, have increasingly received attention due to their potential as mediators of crosstalk between kidneys and different organs, including skeletal muscle. This mini-review summarizes the recent findings that point to the role of exosomes in the cross-talk between kidney and skeletal muscle in CKD. Understanding of the contents and the mechanism of exosome release may prone exosomes be the potential therapeutic targets for CKD.
Background The impact of atmospheric fine particulate matter (PM2.5) and ozone (O3) on the mortality of circulatory system diseases cannot be ignored. However, whether the interaction between PM2.5 ...and O3 can affect population health is rarely reported and requires study. ObjectiveTo investigate the individual and interactive impacts of atmospheric PM2.5 and O3 on the mortality of circulatory system diseases in the population of Ningxia region. Methods The data of 119647 deaths due to circulatory system diseases, daily average concentrations of atmospheric pollutants, and meteorological data in Ningxia from 2013 to 2020 were retrieved. PM2.5 was divided into low, medium, and high concentrations according to the primary and secondary national limits (35 and 75 μg·m−3) of the Ambient air quality standards. Similarly, O3 was divided into low, medium, and high concentrations according to the national limits (100 and 160 μg·m−3). Using a generalized additive mixed model based on quasi Poisson distribution, the impacts of atmospheric PM2.5 and O3 as well as their interaction on the mortality of circulatory system diseases were analyzed using the population data of Ningxia region. Results During the target period, males and the ≥ 65 year group accounted for larger proportions of deaths due to circulatory system diseases (55.47% and 79.87% respectively). The daily average concentration of PM2.5 (40.25 μg·m−3) exceeded the national primary limit. In the single pollution model, the highest cumulative lag effects for mortality from circulatory system diseases were PM2.5 exposure over previous 1 d (lag01) and O3 exposure for previous 2 d (lag02), and their excess risk (ER) values were 1.03% (95%CI: 0.67%, 1.40%) and 1.02% (95%CI: 0.57%, 1.50%), respectively. The results of concentration stratification analysis showed that the most significant risks of death from circulatory system diseases ER (95%CI): 1.12% (0.32%, 1.92%) and 0.95% (0.13%, 1.79%) respectively were found at medium PM2.5 and O3 concentrations. The interaction analysis revealed that under, a synergistic effect on the risk of death from circulatory system diseases was identified (relative excess risk due to interaction=3.08%, attributable proportion of interaction=2.90%, synergy index=1.89) when considering the coexistence of PM2.5 and O3 above the primary limit. As the concentrations of PM2.5 and O3 increased, the synergistic effect increased the risk of death from circulatory system diseases in the general population, men, women, and the ≥ 65 years group. Conclusion Both atmospheric PM2.5 and O3 can increase the risk of death from circulatory system diseases, and the two pollutants have a synergistic effect on the risk of death from circulatory system diseases.
Endovascular thrombectomy (EVT) improves long-term outcomes and decreases mortality in ischemic stroke patients. However, a significant proportion of patients do not benefit from EVT recanalization, ...a phenomenon known as futile recanalization or reperfusion without functional independence (RFI). In this study, we aim to identify the major stroke risk factors and patient characteristics associated with RFI.
This is a retrospective cohort study of 297 consecutive patients with ischemic stroke who received EVT at three academic stroke centers in China from March 2019 to March 2022. Patient age, sex, modified Rankin Scale (mRS), National Institute of Health Stroke Scale (NIHSS), Alberta stroke program early CT score (ASPECTS), time to treatment, risk factors and comorbidities associated with cerebrovascular diseases were collected, and potential associations with futile recanalization were assessed. RFI was successful reperfusion defined as modified thrombolysis in cerebral infarction (mTICI) ≥ 2b without functional independence at 90 days (mRS ≥ 3).
Of the 297 initial patients assessed, 231 were included in the final analyses after the application of the inclusion and exclusion criteria. Patients were divided by those who had RFI (
= 124) versus no RFI (
= 107). Older age (OR 1.041, 95% CI 1.004 to 1.073;
= 0.010), chronic kidney disease (OR 4.399, 0.904-21.412;
= 0.067), and higher 24-h NIHSS (OR 1.284, 1.201-1.373;
< 0.001) were independent predictors of RFI. Conversely, an mTICI score of 3 was associated with a reduced likelihood of RFI (OR 0.402, 0.178-0.909;
= 0.029).
In conclusion, increased age, higher 24-h NIHSS and lack of an mTICI score of 3 were independently associated with RFI and have potential prognostic values in predicting patients that are less likely to respond to EVT recanalization therapy.
Right internal jugular vein (IJV) is a preferred access route for tunneled (cuffed) dialysis catheters (TDCs), and both right external jugular vein (EJV) and left IJV are alternative routes for ...patients in case the right IJV isn't available for TDC placement. This retrospective study aimed to determine if a disparity exists between the two alternative routes in hemodialysis patients in terms of outcomes of TDCs.
49 hemodialysis patients who required TDCs through right EJV (n = 21) or left IJV (n = 28) as long-term vascular access were included in this study. The primary end point was cumulative catheter patency. Secondary end points include primary catheter patency, proportion of patients that never required urokinase and incidence of catheter-related bloodstream infections (CRBSI).
A total of 20,870 catheter-days were evaluated and the median was 384 (interquartile range, 262-605) catheter-days. Fewer catheters were removed in the right EJV group than in the left IJV group (P = 0.007). Mean cumulative catheter patency was higher in the right EJV group compared with the left IJV group (P = 0.031). There was no significant difference between the two groups in the incidence of CRBSI, primary catheter patency or proportion of patients that never required urokinase use. Total indwell time of antecedent catheters was identified as an independent risk factor for cumulative catheter patency by Cox regression hazards test with an HR of 2.212 (95% CI, 1.363-3.588; p = 0.001).
Right EJV might be superior to left IJV as an alternative insertion route for TDC placement in hemodialysis patients whose right IJVs are unavailable.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Diabetes has been listed as one of the three major diseases that endanger human health. Accurately injecting insulin (Ins) depending on the level of blood glucose (LBG) is the standard treatment, ...especially controlling LBG in the long‐term by a single injection. Herein, the pH‐responsive hexa‐histidine metal assembly (HmA) encapsulated with enzymes (GOx and CAT) and Ins (HmA@GCI) is engineered as the vehicle for glucose‐mediated insulin delivery. HmA not only shows high proteins loading efficiency, but also well retained proteins activity and protect proteins from protease damage. Within HmA, the biocatalytic activities of enzymes and the efficiency of the cascade reaction between GOx and CAT are enhanced, leading to a super response to the change of LBG with insulin release and efficient clearance of harmful byproducts of GOx (H2O2). In the treatment of diabetic mice, HmA@GCI reduces LBG to normal in half an hour and maintains for more than 5 days by a single subcutaneous injection, and nearly 24 days with four consecutive injections. During the test period, no symptoms of hypoglycemia and toxicity to tissues and organs are observed. These results indicate that HmA@GCI is a safe and long‐acting hypoglycemic agent with prospective clinical application.
In this work, HmA@GOx@CAT@Ins (HmA@GCI) nanoparticles are prepared under mild conditions. The nanoparticles have high proteins loading capacity and protect proteins from protease. More importantly, HmA@GCI can improve enzyme activity and enhance the efficiency of cascade reaction, and have long‐term hypoglycemic effect in vivo, providing a safe and long‐acting hypoglycemic agent with prospective clinical application.
Melanocortin therapy by using adrenocorticotropic hormone (ACTH) or non-steroidogenic melanocortin peptides attenuates proteinuria and glomerular injury in experimental glomerular diseases and ...induces remission of nephrotic syndrome in patients with diverse glomerulopathies, even those resistant to steroids. The underlying mechanism remains elusive, but the role of melanocortin 1 receptor (MC1R) has been implicated and was examined here. Four patients with congenital red hair color and nephrotic syndrome caused by idiopathic membranous nephropathy or focal segmental glomerulosclerosis were confirmed by gene sequencing to bear dominant-negative MC1R mutations. Despite prior corticosteroid resistance, all patients responded to ACTH monotherapy and ultimately achieved clinical remission, inferring a steroidogenic-independent and MC1R-dispensable anti-proteinuric effect of melanocortin signaling. In confirmatory animal studies, the protective effect of Nle(4), D-Phe(7)-α-melanocyte stimulating hormone (NDP-MSH), a potent non-steroidogenic pan-melanocortin receptor agonist, on the lipopolysaccharide elicited podocytopathy was completely preserved in MC1R-null mice, marked by reduced albuminuria and diminished histologic signs of podocyte injury. Moreover, in complementary in vitro studies, NDP-MSH attenuated the lipopolysaccharide elicited apoptosis, hypermotility and impairment of filtration barrier function equally in primary podocytes derived from MC1R-null and wild-type mice. Collectively, our findings suggest that melanocortin therapy confers a proteinuria reducing and podoprotective effect in proteinuric glomerulopathies via MC1R-independent mechanisms.
As a natural polymer, leather and its associated industries are known to be the leading economic sector in many countries. However, the huge amounts of leather waste generated from the leather ...industry causes severe environmental pollution. Herein, cow leather (CL) powders were prepared using a homemade machine and used as a low-cost adsorbent for the effective removal of reactive dyes from wastewater. The as-prepared CL powders exhibited dot-like, rod-like, and fiber-like morphologies. A Fourier transform infrared analysis and an x-ray diffraction analysis demonstrated that the CL powders retained the main structure of the protein contained in it. In addition, an improvement in thermal stability was also observed for the CL powders. Dye adsorption experiments indicate that the CL powders showed the highly effective removal of C.I. Reactive Red 120 (RR120), C.I. Reactive Yellow 127 (RY127), and C.I. Reactive Blue 222 (RB222) with the adsorption capacity of 167.0, 178.9, and 129.6 mg·g
, respectively. The Langmuir, pseudo-second order, and intraparticle diffusion models could well depict the adsorption equilibrium and kinetics of CL powders toward the investigated reactive dyes. The as-prepared CL powders can be used as a potential adsorbent in the treatment of dye contaminated wastewater. Future studies will mainly focus on the application of the adsorbed CL powders for the pigment printing of textile materials.
Cannabinoid receptors are components of the endocannabinoid system that affect various physiological functions. We aim to investigate the effect of cannabinoid receptor modulation on kidney disease.
...PubMed, Web of Science databases, and EMBASE were searched. Articles selection, data extraction and quality assessment were independently performed by two investigators. The SYRCLE's RoB tool was used to assess the risk of study bias, and pooled SMD using a random-effect model and 95% CIs were calculated. Subgroup analyses were conducted in preselected subgroups, and publication bias was evaluated. We compared the effects of CB1 and CB2 antagonists and/or knockout and agonists and/or genetic regulation on renal function, blood glucose levels, body weight, and pathological damage-related indicators in different models of chronic and acute kidney injury.
The blockade or knockout of CB1 could significantly reduce blood urea nitrogen SMD,- 1.67 (95% CI - 2.27 to - 1.07), serum creatinine SMD, - 1.88 (95% CI - 2.91 to - 0.85), and albuminuria SMD, - 1.60 (95% CI - 2.16 to - 1.04) in renal dysfunction animals compared with the control group. The activation of CB2 group could significantly reduce serum creatinine SMD, - 0.97 (95% CI - 1.83 to - 0.11) and albuminuria SMD, - 2.43 (95% CI - 4.63 to - 0.23) in renal dysfunction animals compared with the control group.
The results suggest that targeting cannabinoid receptors, particularly CB1 antagonists and CB2 agonists, can improve kidney function and reduce inflammatory responses, exerting a renal protective effect and maintaining therapeutic potential in various types of kidney disease.
Groundwater is an important source for drinking, agricultural, and industrial purposes in the Linfen basin of the Eastern Chinese Loess Plateau (ECLP). To ensure the safety of drinking water, this ...study was carried out to assess the quality using the water quality index (WQI) and potential health risks of groundwater using the human health risk assessment model (HHRA). The WQI approach showed that 90% of the samples were suitable for drinking, and Pb, TH, F−, SO42−, and TDS were the most significant parameters affecting groundwater quality. The non-carcinogenic health risk results indicated that 20% and 80% of the samples surpassed the permissible limit for adult females and children. Additionally, all groundwater samples could present a carcinogenic health risk to males, females, and children. The pollution from F−, Pb, and Cr6+ was the most serious for non-carcinogenic health risk. Cd contributed more than Cr6+ and As to carcinogenic health risks. Residents living in the central of the study area faced higher health risks than humans in other areas. The research results can provide a decision-making basis for the scientific management of the regional groundwater environment and the protection of drinking water safety and public health.
Background: Epithelial-mesenchymal transition (EMT) is recognized to play an important role in diabetic nephropathy (DN). Objective: To analyze the roles of glycogen synthase kinase 3β (GSK-3β), ...β-catenin and Snail signaling in high glucose (HG)-induced mouse podocytes EMT. Methods: Differentiated podocytes were divided into: the normal glucose group (NG: glucose 5.6mM), the HG groups (12.5HG: 12.5mM; 25HG: 25mM; and 50HG: 50mM of glucose), and the osmotic control group (NG+M: glucose 5.6mM and mannitol 44.4mM). GSK-3β, β-catenin and Snail were assessed using semi-quantitative RT-PCR, western blot and immunofluorescence. β-catenin and Snail pathways were assessed after down-regulating GSK-3β expression using an inhibitor (LiCl) or a small-interfering RNA (siRNA). Results: HG increased GSK-3β, β-catenin and Snail expressions, and promoted EMT, as shown by decreased nephrin expression (epithelial marker), and increased α-SMA expression (mesenchymal marker). GSK-3β inhibitor and GSK-3β siRNA decreased β-catenin and Snail expressions, and reversed HG-induced EMT. Immunofluorescence showed that GSK-3β and β-catenin did not completely overlap; β-catenin was transferred to the nucleus in the 25HG group. VDR seems to be involved in HG-induced β-catenin nuclear translocation. Conclusion: Down-regulating GSK-3β expression decreased β-catenin and Snail expression and reversed HG-induced podocytes EMT. Thus, modulating GSK-3β might be a target to slow or prevent DN.
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