Cisplatin (CP)-induced nephrotoxicity is widely accepted as a model for acute kidney injury (AKI). Although cisplatin-induced chronic kidney disease (CKD) in rodent has been reported, the role of ...phosphate in the cisplatin-induced CKD progression is not described. In this study, we gave a single peritoneal injection of CP followed by high (2%) phosphate diet for 20 weeks. High dose CP (20 mg/Kg) led to high mortality; whereas a lower dose (10 mg/Kg) resulted in a full spectrum of AKI with tubular necrosis, azotemia, and 0% mortality 7 days after CP injection. After consuming a high phosphate diet, mice developed CKD characterized by low creatinine clearance, interstitial fibrosis, hyperphosphatemia, high plasma PTH and FGF23, low plasma 1,25(OH)2 Vitamin D3 and αKlotho, and classic uremic cardiovasculopathy. The CP model was robust in demonstrating the effect of aging, sexual dimorphism, and dietary phosphate on AKI and also AKI-to-CKD progression. Finally, we used the CP-high phosphate model to examine previously validated methods of genetically manipulated high αKlotho and therapy using exogenous soluble αKlotho protein supplementation. In this CP CKD model, αKlotho mitigated CKD progression, improved mineral homeostasis, and ameliorated cardiovascular disease. Taken together, CP and high phosphate nephrotoxicity is a reproducible and technically very simple model for the study of AKI, AKI-to-CKD progression, extrarenal complications of CKD, and for evaluation of therapeutic efficacy.
A high phosphate diet accelerates cisplatin–induced acute kidney injury (AKI) progression to chronic kidney disease (CKD). Aging, male gender, and Klotho deficiency exacerbate and Klotho administration mitigates CKD progression, mineral disorders, and cardiovasculopathy. This is a technically simple model to study AKI-to-CKD transition, complications of CKD, and potential therapies.
Dihydroartemisinin (DHA) has been found to inhibit the expression of von Willebrand factor (VWF), a marker of endothelial cell injury, but its mechanism in cerebral ischemia/reperfusion (I/R) injury ...remains obscure. In this study, I/R model was constructed through middle cerebral artery occlusion (MCAO) in rats, followed by DHA administration. The effect of DHA on rat cerebral I/R injury was investigated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin and eosin staining, TUNEL staining, and Western blot. Brain microvascular endothelial cells (BMVECs) isolated from newborn rats were exposed to oxygen–glucose deprivation/reoxygenation (OGD/R), and then treated with DHA. The results showed that MCAO treatment induced infarction, nerve cell apoptosis, and brain tissue impairment in rats, which was mitigated by DHA. OGD/R inhibited viability and accelerated apoptosis of BMVECs, which was alleviated by DHA. I/R procedures or OGD/R up-regulated expressions of VWF, ATG7, Beclin1, and LC3-II/LC3-I ratio, while down-regulating Occludin, Claudin-5, ZO-1, P62, SIRT1, and FOXO1 expressions
and
; however, these effects of I/R procedures or OGD/R were offset by DHA. VWF overexpression reversed the above effects of DHA on OGD/R-induced BMVECs. In summary, DHA ameliorates cerebral I/R injury in rats by reducing VWF level and activating autophagy-mediated SIRT1/FOXO1 signaling pathway.
Abstract
Background
Ischemia–reperfusion injury (IRI)-induced acute kidney injury (AKI) can repair itself completely. However, most moderate and severe patients undergoing IRI-AKI progress to chronic ...kidney disease due to incomplete repair. The present study is aimed to investigate the role of bone marrow mesenchymal stem cell-derived exosomes (MSC-Exo) with indoleamine 2,3-dioxygenase (IDO) overexpression on incomplete repair in mice after IRI.
Methods
IRI mice was established by clamping the unilateral renal pedicles and challenged with MSC-Exo. Blood biochemical indexes and inflammation factors contents were measured by ELISA assay. Histopathological examinations were monitored by HE, Masson, Immunohistochemical and TUNEL staining. Immunofluorescence, flow cytometry and immunoblotting were used to detect the polarization of macrophages, respectively.
Results
As compared to sham operation mice, IRI mice showed high contents of serum BUN and Scr, and more severe damaged kidney tissues on days 1 and 3, which all gradually declined over time, showing the lowest level on day 7 after injury. Once treated with MSCs-Exo that could directly transfer to kidney tubular cells, the restoration of kidney functions significantly accelerated by contrast to IRI mice, and the promotive effects were more obvious in IDO-overexpressed MSCs-Exo (MSCs-Exo-IDO)-treated IRI mice. Furthermore, MSCs-Exo-IDO administration also accelerated renal tubular cells proliferation, restrained tubular cells apoptosis, fibrosis and inflammation factor secretions during self-repair process compared to IRI mice, whose effects were higher than MSCs-Exo-NC-challenged IRI mice and IDO overexpressing plasmid-injected IRI mice. Mechanistically, MSCs-Exo-NC and MSCs-Exo-IDO exposure promoted the polarization from M1 macrophage to M2 macrophage, leading to more anti-inflammatory factors production, and subsequently altered the inflammatory microenvironment of renal tubular cells, which facilitated the self-repair process in mice after IRI.
Conclusion
MSCs-derived exosome accelerated renal self-repair in IRI mice by activating M2 macrophages polarization, which effects were amplified by IDO overexpression in MSCs. Potentially, genetically modified MSCs-Exo is an effective approach to improve renal self-repair in IRI-AKI mice.
Increasing evidence suggests that macrophage polarization is involved in the recovery from ischemia-reperfusion (I/R)-induced acute kidney injury (AKI), implying that the regulation of macrophage ...polarization homeostasis might mediate AKI recovery. Trib1 is a key regulator of macrophage differentiation, but its role in AKI remains unclear. Here, we aimed to investigate the role of Trib1 and its link with the macrophage phenotype in the process of adaptive recovery from I/R-induced renal injury. Lentiviral vector-mediated RNA interference (RNAi) was used to knock down Trib1 expression
and
, and a mouse model of moderate AKI was established by the induction of I/R injury. Renal function measurements and inflammatory factors were determined by the corresponding kits. Histomorphology was assessed by hematoxylin-eosin, Masson and PAS staining. Western blot and flow cytometry were employed for the analysis of signal transduction, cell apoptosis and macrophage phenotypes. Trib1 knockdown inhibited cell viability of tubular epithelial cells (TECs) by inhibiting proliferation and enhancing apoptosis
. I/R-induced AKI significantly impaired renal function in mice via increasing the levels of BUN, Scr, NGAL and renal tubular damage, leading to renal fibrosis from days 1 to 3. Through the adaptive self-repair mechanism, renal dysfunction recovered over time and returned to almost normal levels on day 28 after I/R intervention. However, Trib1 depletion worsened renal damage on day 3 and blunted the adaptive repair process of the renal tissue. Mechanistically, Trib1 inhibition suppressed renal tubular cell proliferation under adaptive self-repair conditions by affecting the expression of the proliferation-related proteins cyclin D1, cyclin B, p21, and p27, the apoptosis-related proteins Bcl-2 and Bax, and the fibrosis-related proteins collagen I and III. Furthermore, the M1/M2 macrophage ratio increased in the first 3 days and decreased from day 7 to day 28, consistent with changes in the expression of inflammatory factors, including TNFα, IL-6, IL-12, IL-10, and IL-13. Trib1 inhibition blocked macrophage polarization during adaptive recovery from I/R-induced moderate AKI. Our results show that Trib1 plays a role in kidney recovery and regeneration via the regulation of renal tubular cell proliferation by affecting macrophage polarization. Thus, Trib1 might be a viable therapeutic target to improve renal adaptive repair following I/R injury.
Depression and anxiety are common comorbidities in cardiovascular clinic outpatients. Timely identification and intervention of these mental and psychological disorders can contribute to correct ...diagnosis, better prognosis, less medical expenses, and improved quality of life. The convenience of online doctor-patient communication platforms has increasingly attracted patients to online consultations. However, online health care and offline health care are very different. Research on how to identify psychological disorders in patients who engage in an online cardiology consultation is lacking. This study aimed to explore the feasibility of using a self-rating scale to assess mental illness among patients who consult with a cardiologist online and to compare the differences in anxiety and depression between online and offline patients. From June 2022 to July 2022, we conducted follow-up visits with 10,173 patients on the Haodf platform. We conducted detailed consultations with 286 patients who visited the same cardiologist in the outpatient department. We used the self-rated Generalized Anxiety Disorder (GAD-7) and Patient Health Questionnaire (PHQ-9) scales to assess anxiety and depression, respectively. We analyzed the influencing factors related to the degree of coordination of online patients. We also compared the prevalence of anxiety or depression between online and offline patients and analyzed the factors related to anxiety or depression. Of the 10,173 online consultation patients, only 186 (1.8%) responded effectively. The response rate of the offline consultation patients was 96.5% (276/286). Frequent online communication and watching live video broadcasts were significantly related to effective responses from online patients (P<.001). The prevalence of anxiety (70/160, 43.7% vs 69/266, 25.8%; P<.001) or depression (78/160, 48.7% vs 74/266, 27.7%; P<.001) in online consultation patients was significantly higher than that in offline patients. In bivariate analyses, the factors related to anxiety included female sex, unemployment, no confirmed cardiovascular disease, and the online consultation mode, while smokers and those who underwent COVID-19 quarantine were less likely to present with anxiety. The factors related to depression included female sex, divorced or separated individuals, and the online consultation mode. COVID-19 quarantine was related with a lower likelihood of depression. BMI was negatively correlated with depression. In multiple ordered logistic regression analysis, women were more likely than men to present with anxiety (odds ratio OR 2.181, 95% CI 1.365-3.486; P=.001). Women (OR 1.664, 95% CI 1.082-2.559; P=.02) and online patients (OR 2.631, 95% CI 1.305-5.304; P=.007) were more likely to have depression. Online patients had more anxiety or depression than offline patients. Anxiety was more prevalent in women, the unemployed, and those without confirmed cardiovascular disease. Women and divorced or separated individuals were more prone to depression. Increasing the frequency of doctor-patient communication and participating in video interactions can help improve patient cooperation.
•SPI gel can be prepared by probiotic fermentation.•Acidifications lead to gelation of SPI.•Excessive fermentation reduces of porosity of the gel.
Soy protein isolate (SPI) was used to prepare gels ...through probiotic fermentation. The effects of fermentation time (0–20 h) on the physicochemical properties of resulting gel were evaluated. The effect of probiotic fermentation on physicochemical properties of gel was found to highly depend on the fermentation time. The probiotic fermentation decreased the pH value below pH 4.75 and this process also induced SPI to form a gel upon 10 h. The formation of gel was indicated by the increase of particle size, viscosity and storage modulus, and appearance of a new peak in molecular weight distribution. The formation of porous and gel-like microstructure, due to the aggregation of SPI molecules, also occurred after 10 h of fermentation. Water holding capacity of SPI-based gel reached the highest value at 15 h fermentation and decreased with further fermentation. The probiotic fermentation caused an increase of band intensity of amide-A in FTIR spectra. It also caused a decrease of surface hydrophobicity and fluorescence intensity in intrinsic tryptophan fluorescence spectra. The subunits of SPI remained intact and were not affected by probiotic fermentation.
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Cisplatin-induced acute kidney injury (CIAKI) is a common complication in patients receiving cisplatin-based chemotherapy. But the effective therapies for CIAKI are not available. Retinoic acid (RA), ...the main derivative of vitamin A, has the potential to reduce inflammation and fibrosis in renal injury. However, the effect and mechanism of RA on CIAKI are still unclear. The aim of this study is to investigate whether RA can alleviate CIAKI through activation of autophagy. In this study, we evaluated the effect of RA, RA’s effect on autophagy and apoptosis after cisplatin-induced injury on renal tubular epithelial cells (RTECs) by LDH assay, immunoblotting and TUNEL staining. Then we established Atg5
flox/flox
:Cagg-Cre mice in which Cagg-Cre is tamoxifen inducible, and Atg5 is conditional deleted after tamoxifen injection. The effect of RA and RA’s effect on autophagy on CIAKI model were evaluated by biochemical assessment, hematoxylin and eosin (HE) staining, and immunoblotting in the control and autophagy deficient mice.
In vitro
, RA protected RTECs against cisplatin-induced injury, activated autophagy, and inhibited cisplatin-induced apoptosis.
In vivo
, RA attenuated cisplatin-induced tubular damage, shown by improved renal function, decreased renal cast formation, decreased NGAL expression, and activated autophagy in the control mice. Furthermore, the nephrotoxicity of cisplatin was aggravated, and the protective effect of RA was attenuated in autophagy deficient mice, indicating that RA works in an autophagy-dependent manner on CIAKI. RA activates autophagy and alleviates CIAKI
in vivo
and
in vitro
.Thus RA may be a renoprotective adjuvant for cisplatin-based chemotherapy.
Abstract
Objective
To investigate the correlation between serum level of homocysteine (Hcy) and ulcerative colitis (UC) and evaluate its diagnostic performance by pooling the open published data.
...Methods
The case–control or cohort studies relevant to serum level of Hcy and UC, published in Pubmed, Medline, EMBASE, China Wanfang and CNKI databases, were systematically screened by using the text word of “homocysteine,” “hcy,” “UC,” “inflammatory bowel disease.” The standard mean difference (SMD) was pooled through random effect model. The diagnostic sensitivity, specificity and area under the receiver operating characteristic (AUC) curve of serum Hcy for UC were also calculated.
Results
Eighteen relevant case–control studies were identified by electronic searching the related databases. The pooled results indicated that the serum levels of Hcy were statical different between UC and healthy controls with SMD = 0.95 (95% CI: 0.87–1.04). The serum levels of Hcy were 14.30 ± 3.08 (range: 10.10–21.73) and 10.09 ± 1.57 (range: 6.80–12.47) μmol/L for UC and healthy controls, respectively, of the included 18 studies. Using serum Hcy as biomarker for UC identification, the diagnostic sensitivity, specificity and AUC were 94.44% (95% CI: 72.71–99.86%), 72.22% (46.52–90.31%) and 0.88 (95% CI: 0.77–0.99,
P
< 0.05), respectively. Significant publication bias was identified in the present work.
Conclusion
Based on the present publications, serum Hcy was elevated in UC cases and can be applied as serological marker for UC diagnosis. However, due to significant publication bias, the diagnostic performance should be further validated by well-designed prospective diagnostic studies.
Microelectromechanical system (MEMS) pressure sensors based on silicon are widely used and offer the benefits of miniaturization and high precision. However, they cannot easily withstand high ...temperatures exceeding 150 °C because of intrinsic material limits. Herein, we proposed and executed a systematic and full-process study of SiC-based MEMS pressure sensors that operate stably from -50 to 300 °C. First, to explore the nonlinear piezoresistive effect, the temperature coefficient of resistance (TCR) values of 4H-SiC piezoresistors were obtained from -50 to 500 °C. A conductivity variation model based on scattering theory was established to reveal the nonlinear variation mechanism. Then, a piezoresistive pressure sensor based on 4H-SiC was designed and fabricated. The sensor shows good output sensitivity (3.38 mV/V/MPa), accuracy (0.56% FS) and low temperature coefficient of sensitivity (TCS) (-0.067% FS/°C) in the range of -50 to 300 °C. In addition, the survivability of the sensor chip in extreme environments was demonstrated by its anti-corrosion capability in H
SO
and NaOH solutions and its radiation tolerance under 5 W X-rays. Accordingly, the sensor developed in this work has high potential to measure pressure in high-temperature and extreme environments such as are faced in geothermal energy extraction, deep well drilling, aeroengines and gas turbines.
The deployment of low earth orbits is seen as a promising way of enlarging data capacities as well as high data rates. Catering to these interests, optical communication presents possible ways of ...larger bandwidth than microwave communication. The current generation of mainstream communication systems are classified as coherent systems and incoherent systems, and in particular, coherent systems have received more attention owing to their high receiving sensitivity. This study investigates a digital coherent transceiver, based on binary phase-shift keying technology. As coherent demodulation will be affected by considering the Doppler shift effect in digital demodulation, Doppler shift of ± GHz can be compensated by adopting a two-stage frequency offset compensation. Moreover, by leveraging a fast filtering algorithm a considerable amount of resource consumption is saved in its engineering implementation, and its sensitivity can be significantly enhanced
via
a high-speed parallel error-correction codec based on low-density parity-check technology.
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