Detection of iodixanol-induced allergic reaction signals in Chinese inpatients: a multi-center retrospective database study using prescription sequence symmetry analysis.

Objective: This study aimed to explore the signal detection method for allergic reactions induced by inpatient iodixanol injection. Methods: A database of 3,719,217 hospitalized patients from 20 large Chinese general hospitals was processed and analyzed using the prescription sequence symmetry analysis (PSSA) method. Results: 126,680 inpatients who used iodixanol and were concurrently treated with anti-allergic drugs were analyzed. In the medical records of these patients, only 32 had documented iodixanol allergies. Statistical analysis identified 22 drugs in 4 categories-calcium preparations, adrenergic/dopaminergic agents, glucocorticoids, and antihistamines-as marker drugs. With time intervals of 3, 7, and 28 days, the adjusted sequence ratios (aSRs) for all anti-allergics and the 4 categories were greater than 1. The 7-day aSRs were 2.12 (95% CI: 2.08-2.15), 1.70 (95% CI: 1.68-1.73), 3.85 (95% confidence interval [CI]: 3.75-2.30), 2.30 (95% CI: 2.26-2.35), and 1.95 (95% CI: 1.89-2.02), respectively. The proportions of adverse drug events indicated by each signal were as follows: all anti-allergics (2.92%-3%), calcium gluconate (0.19%-0.52%), adrenergic/dopaminergic agents (2.20%-3.37%), glucocorticoids (3.13%-3.76%), and antihistamines (1.05%-1.32%). Conclusion: This first multi-center Chinese inpatient database study detected iodixanol-induced allergy signals, revealing that reactions may be much higher than those in collected spontaneous reports. Iodixanol risk exposure was closer to actual pharmaceutical care findings. PSSA application with ≤7-day intervals appears better suited for monitoring late allergic reaction signals with these drugs.

Inflammation Is More Sensitive than Cell Proliferation in Response to Rapamycin Treatment in Polycystic Kidney Disease.

INTRODUCTION: It has been reported that rapamycin inhibited inflammation in renal interstitial diseases. We therefore hypothesized that rapamycin could attenuate inflammation in polycystic kidney disease (PKD). METHODS: Han:SPRD rats were treated with rapamycin by daily gavage from 4 weeks to 12 weeks of age at the dosage of 0.5 mg/kg/day (low dose) or 1 mg/kg/day (high dose). WT9-12 human PKD cells were treated with various concentrations of rapamycin. RESULTS: Two-kidney/total body weight ratio and cystic index in Cy/+ kidneys were significantly reduced with the treatment of low-dose rapamycin and further reduced by the treatment with high-dose rapamycin. However, the renal function of Cy/+ rats was equally improved by the treatment with either low-dose or high-dose rapamycin. The renal cell proliferation was significantly decreased in Cy/+ kidneys with the treatment of low-dose rapamycin and was further decreased with the treatment of high-dose rapamycin as examined by Ki67 staining. The phosphorylation of S6K in cystic kidneys was decreased by low-dose rapamycin and further decreased by high-dose rapamycin. Both low-dose and high-dose rapamycin treatment decreased macrophage infiltration and the expression of complement factor B (CFB), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor-alpha (TNF-α) to a similar level. The expression of CFB, MCP-1, and TNF-α and phosphorylation of S6K were inhibited in WT9-12 cells treated with 10 nm rapamycin at 24 h and 48 h, respectively. Moreover, the phosphorylation of Akt was not increased by 1 nm and 10 nm of rapamycin and enhanced by 1 µm rapamycin treatment. Interestingly, WT9-12 cell proliferation could be inhibited by 1 µm rapamycin. CONCLUSION: Low dose of rapamycin could inhibit inflammation and protect renal function in PKD. Inflammation is more sensitive than cell proliferation in response to rapamycin treatment in PKD.

In-depth exploration of the shared genetic signature and molecular mechanisms between end-stage renal disease and osteoporosis.

Background: Osteoporosis (OS) and fractures are common in patients with end-stage renal disease (ESRD) and maintenance dialysis patients. However, diagnosing osteoporosis in this population is challenging. The aim of this research is to explore the common genetic profile and potential molecular mechanisms of ESRD and OS. Methods and results: Download microarray data for ESRD and OS from the Gene Expression Omnibus (GEO) database. Weighted correlation network analysis (WGCNA) was used to identify co-expression modules associated with ESRD and OS. Random Forest (RF) and Lasso Regression were performed to identify candidate genes, and consensus clustering for hierarchical analysis. In addition, miRNAs shared in ESRD and OS were identified by differential analysis and their target genes were predicted by Tragetscan. Finally, we constructed a common miRNAs-mRNAs network with candidate genes and shared miRNAs. By WGCNA, two important modules of ESRD and one important module of OS were identified, and the functions of three major clusters were identified, including ribosome, RAS pathway, and MAPK pathway. Eight gene signatures obtained by using RF and Lasso machine learning methods with area under curve (AUC) values greater than 0.7 in ESRD and in OS confirmed their diagnostic performance. Consensus clustering successfully stratified ESRD patients, and C1 patients with more severe ESRD phenotype and OS phenotype were defined as "OS-prone group". Conclusion: Our work identifies biological processes and underlying mechanisms shared by ESRD and OS, and identifies new candidate genes that can be used as biomarkers or potential therapeutic targets, revealing molecular alterations in susceptibility to OS in ESRD patients.

TSPLASSO: A Two-stage Prior LASSO Algorithm for Gene Selection using Omics Data.

Feature selection has been extensively applied to identify cancer genes using omics data. Although substantial studies have been conducted to search for cancer genes, the available rich knowledge on various cancers is seldom used as prior information in feature selection. This paper proposes a two-stage prior LASSO (TSPLASSO) method, which represents an early attempt in designing feature selection algorithms using prior information. The first stage performs gene selection via linear regression with LASSO. Candidate genes that are correlated with known cancer genes are retained for subsequent analysis. The second stage establishes a logistic regression model with LASSO to realize final cancer gene selection and sample classification. The key advantages of TSPLASSO include the successive consideration of prior cancer genes and binary sample types as response variables in stages one and two, respectively. In addition, the TSPLASSO performs sample classification and variable selection simultaneously. Compared with six state-of-the-art algorithms, numerical simulations in six real-world datasets show that TSPLASSO can improve the accuracy of variable selection by 5%-400% in the three bulk sequencing datasets and the scRNA-seq dataset; and the performance is robust against data noise and variations of prior cancer genes. The TSPLASSO provides an efficient, stable and practical algorithm for exploring biomedcial and health informatics from omics data.

Application of CRISPR/Cas9-based genome editing in ecotoxicology.

Chemicals are widely used and released into the environment, and their degradation, accumulation, migration, and transformation processes in the environment can pose a threat to the ecosystem. The advancement in analytical methods with high-throughput screening of biomolecules has revolutionized the way toxicologists used to explore the effects of chemicals on organisms. CRISPR/Cas is a newly developed tool, widely used in the exploration of basic science and biologically engineered products given its high efficiency and low cost. For example, it can edit target genes efficiently, and save loss of the crop yield caused by environmental pollution as well as gain a better understanding of the toxicity mechanisms from various chemicals. This review briefly introduces the development history of CRISPR/Cas and summarizes the current application of CRISPR/Cas in ecotoxicology, including its application on improving crop yield and drug resistance towards agricultural pollution, antibiotic pollution and other threats. The benefits by applying the CRISPR/Cas9 system in conventional toxicity mechanism studies are fully demonstrated here together with its foreseeable expansions in other area of ecotoxicology. Finally, the prospects and disadvantages of CRISPR/Cas system in the field of ecotoxicology are also discussed.

Early oral nutritional supplement improves COVID-19 outcomes among hospitalized older patients during the Omicron wave.

OBJECTIVES: The effect of and optimal timing for initiating an oral nutritional supplement(ONS) in hospitalized older patients with the Omicron variant infection remain unclear. The aim of this study was to explore the associations between the ONS and clinical outcomes. METHODS: This study used a retrospective cohort design as primary analysis and a case-control design as sensitivity analysis. We collected data from patients with confirmed coronavirus disease 2019 (COVID-19) between April 2022 and June 2022 at Shanghai Fourth People's Hospital, one of the designated medical centers for COVID-19 in Shanghai, China. Patients were identified as ONS users or non-ONS users, with the former defined as early ONS (ONS initiated within 48 h from hospital admission), and late ONS (ONS initiated after 48 h) users. RESULTS: The study included 1181 hospitalized patients ≥60 y of age. The mean age of the cohort was 78 y, and most patients were women (57.7%). Mortalities after propensity-score matching were 1.2% and 4.3% in the ONS group and non-ONS groups, respectively (P = 0.032). Subgroup analysis results showed that median (IQR) hospital length of stay and the median (IQR) length from symptom onset to viral clearance were shorter for the early ONS than for the late ONS group (9 [6-13] d versus 14 [11 -18] d; P < 0.001, and 11 [8-17] d versus 17 [13-22] d; P < 0.001, respectively). The findings from the case-control analysis supported those from the primary analysis. CONCLUSIONS: Early ONS might have significantly lowered risk for in-hospital death, as well as reduce hospital length of stay and days of viral clearance in older patients with COVID-19 during the Omicron wave.

miR-21-5p in extracellular vesicles obtained from adipose tissue-derived stromal cells facilitates tubular epithelial cell repair in acute kidney injury.

BACKGROUND AIMS: Acute kidney injury (AKI) is often associated with poor patient outcomes. Extracellular vesicles (EVs) have a marked therapeutic effect on renal recovery. This study sought to explore the functional mechanism of EVs from adipose tissue-derived stromal cells (ADSCs) in tubular epithelial cell (TEC) repair in AKI. METHODS: ADSCs were cultured and EVs were isolated and identified. In vivo and in vitro AKI models were established using lipopolysaccharide (LPS). RESULTS: EVs increased human kidney 2 (HK-2) cell viability; decreased terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells and levels of kidney injury molecule 1, cleaved caspase-1, apoptosis-associated speck-like protein containing a CARD, gasdermin D-N, IL-18 and IL-1ß; and elevated pro-caspase-1. EVs carried miR-21-5p into LPS-induced HK-2 cells. Silencing miR-21-5p partly eliminated the ability of EVs to suppress HK-2 cell pyroptosis and inflammation. miR-21-5p targeted toll-like receptor 4 (TLR4) and inhibited TEC pyroptosis and inflammation after AKI by inhibiting TLR4. TLR4 overexpression blocked the inhibitory effects of EVs on TEC pyroptosis and inflammation. EVs suppressed the nuclear factor-κB/NOD-like receptor family pyrin domain-containing 3 (NF-κB/NLRP3) pathway via miR-21-5p/TLR4. Finally, AKI mouse models were established and in vivo assays verified that ADSC-EVs reduced TEC pyroptosis and inflammatory response and potentiated cell repair by mediating miR-21-5p in AKI mice. CONCLUSIONS: ADSC-EVs inhibited inflammation and TEC pyroptosis and promoted TEC repair in AKI by mediating miR-21-5p to target TLR4 and inhibiting the NF-κB/NLRP3 pathway.

A Biomimetic Metal-Organic Framework Nanosystem Modulates Immunosuppressive Tumor Microenvironment Metabolism to Amplify Immunotherapy.

In the immunosuppressive tumor microenvironment (iTME), lactate secretion by cancer cells facilitates cell escape via M1 to M2 macrophage polarization, and T cell exhaustion. Therefore, lactate is a promising tumor immunotherapy target. In this study, we constructed a biomimetic nanosystem to modulate iTME metabolism to amplify immunogenic cell death (ICD)-induced immunotherapy. Metal-organic frameworks were coated with platelet membranes (PM) for tumor site-specific delivery and rationally designed to carry lactate oxidase (Lox) which catalytically consumed lactate, while oxaliplatin (Oxa) induced ICD. Due to PM-mediated targeting, the biomimetic nanosystem selectively accumulated in tumors and inhibited tumor growth. Encouragingly, due to effective iTME modulation, enhanced cytotoxic T cell infiltration in tumors was observed. Also, tumor-associated macrophage (TAM) phenotypes were polarized from M2 to M1 types, and regulatory T cell (Treg) levels decreased in vivo. Increased CD8+ T to CD4+ T cell ratios in peripheral blood and spleen were also observed. Thus, our biomimetic nanosystem effectively modulated the iTME and inhibited tumor growth by consuming lactate and amplifying ICD-induced immunotherapy. We provide new avenues into cancer immunotherapy, with a specific emphasis on iTME modulation, which lays the foundation for translational biomimetic nanosystems in clinical settings.

Identification of CKD, bedridden history and cancer as higher-risk comorbidities and their impact on prognosis of hospitalized Omicron patients: a multi-centre cohort study.

To further describe the effect of the "fragile population" and their "higher-risk" comorbidities on prognosis among hospitalized Omicron patients, this observational cohort study enrolled hospitalized patients confirmed with SARS-CoV-2 during the 2022 Omicron wave in Shanghai, China. The primary outcome was progression to severe or critical cases. The secondary outcome was viral shedding time from the first positive SARS-CoV-2 detection. A total of 847 participants were enrolled, most of whom featured as advanced age (>70 years old: 30.34%), not fully vaccinated (55.84%), combined with at least 1 comorbidity (65.41%). Multivariate cox regression suggested age >70 years old (aHR[95%CI] 0.78[0.61-0.99]), chronic kidney disease (CKD) stage 4-5 (aHR[95%CI] 0.61[0.46-0.80]), heart conditions (aHR[95%CI] 0.76[0.60-0.97]) would elongate viral shedding time and fully/booster vaccination (aHR[95%CI] 1.4 [1.14-1.72]) would shorten this duration. Multivariate logistic regression suggested CKD stage 4-5 (aHR[95%CI] 3.21[1.45-7.27]), cancer (aHR[95%CI] 9.52[4.19-22.61]), and long-term bedridden status (aHR[95%CI] 4.94[2.36-10.44]) were the "higher" risk factor compared with the elderly, heart conditions, metabolic disorders, isolated hypertension, etc. for severity while female (aHR[95%CI] 0.34[0.16-0.68]) and fully/booster Vaccination (aHR[95%CI] 0.35[0.12-0.87]) could provide protection from illness progression. CKD stage 4-5, cancer and long-term bedridden history were "higher-risk" factors among hospitalized Omicron patients for severity progression while full vaccination could provide protection from illness progression.

Microneedle Patch Delivery of Methotrexate-Loaded Albumin Nanoparticles to Immune Cells Achieves a Potent Antipsoriatic Effect.

Introduction: Transdermal drug delivery provides a desirable alternative method of penetrating the skin for psoriasis treatment, by virtue of its ability to dampen the overactivation of immune cells and inflammation, while attenuating the detrimental effects of systemic administration. Lymph nodes (LNs), as a critical organ of the lymphatic and the acquired immune system, are suitable sites for drug homing to suppress the immune cells. Methods: In this context, we developed a microneedle (MN) patch that delivers nanodrugs locally to LNs for improving the antipsoriatic treatment. In this study, human serum albumin nanoparticles carrying methotrexate (HM) were synthesized and loaded into hyaluronic acid (HA)-based microneedles (HM/MN). Results: The patch showed an excellent ability to pierce the skin, which enhanced drug delivery. In a mouse model of psoriasis, the HM/MN patch significantly prevented the erythema with decreased skin thickness, thus inhibiting the progression of psoriasis. Further analysis for immune cells in LNs, the percent of dendritic cells (DC) and T cells reduced after the local treatment with HM/MN. Notably, the feasibility of targeted delivery of methotrexate to LNs using nanoparticles was verified by detecting increased accumulation of methotrexate in LNs. In addition, the HM/MN patch pronouncedly decreased the levels of tumor necrosis factor α and interleukin 6 in the skin. Conclusion: The results suggested the high efficacy of using the HM/MN patch to treat psoriasis, and provided new insight into the mechanism of the transdermal drug delivery system.

Regulation of mitophagy through HIF-1α/miR-140-5p/PARKIN axis in acute kidney injury.

Mitochondria homeostasis plays an important role in acute kidney injury (AKI). In this study, we aimed at identifying the mechanism of mitophagy regulation in AKI. Activation of mitophagy after ischemic kidney injury was visualized with increased expression of LC3, PINK1, PARKIN expression and with a subsequent decline in p62 levels. Immuohistochemistry staining showed higher LC3 levels in ischemic kidney injury mice. Further, differential expression of PARKIN targeting miRNAs revealed that miR-140-5p was significantly downregulated followed by ischemic kidney injury. miR-140-5p mimics suppressed PARKIN expressions and their mitochondrial translocation. Further, miR-140-5p mimics under hypoxia prevented mitophagosome formation. These effects on hypoxia-induced PARKIN expression and LC3/TOMM20 levels were reversed by antagomiR miR-140-5p treatment. Dual-luciferase reporter assay revealed that miR-140-5p had significant interaction with 3'UTR of PARKIN. Our findings show that HIF-1α is bound to miR-140-5p promoter and down regulates its expression and thereby promotes mitophagy process under hypoxic conditions. These results cumulatively show that HIF-1α regulates mitophagy during AKI through the regulation of miR-140-5p/PARKIN axis.

The influence of multidisciplinary team clinic on the prognosis of patients with chronic kidney disease.

Chronic kidney disease (CKD) seriously affects the quality of life and survival time of patients, and even affects social and national economic development. In China, how to effectively control the disease process of CKD outpatients has not been determined. A retrospective analysis was made to 100 patients with CKD. Fifty patients treated with traditional clinical treatment were in the control group, and the other fifty patients treated with multidisciplinary team (MDT) clinical treatment were in the MDT group. The prognosis of the two groups after treatment was compared, including glomerular filtration rate (GFR), number of renal replacement treatments, and mortality, to evaluate the actual effect of MDT clinic. CKD patients in the MDT group received the MDT clinic for 24 months. There was no significant difference between GFR and serum creatinine level before treatment, and the quality of life was significantly higher than before. In the control group, the GFR declined more dramatically, the serum creatinine level was higher, and the quality of life was lower than before (P < 0.05). The frequency of renal replacement therapy and mortality in the MDT group were significantly lower than those in the control group (P < 0.05). MDT clinic can effectively improve the prognosis of patients with CKD, delay kidney disease progression, and reduce mortality.

The Effect of Sodium Thiosulfate on Coronary Artery Calcification in Hemodialysis Patients.

This study aimed to effectively control the disease process of hemodialysis outpatients. Hemodialysis secondary hyperparathyroidism patients were randomly divided into the control group and treatment group. The control group was treated with routine treatment, and the treatment group was treated with sodium thiosulfate based on the control group. The changes of serum calcium, phosphorus, whole parathyroid hormone, calcium-phosphorus product and coronary artery calcification (CAC) score, as well as the relief of clinical symptoms, postoperative complications and recurrence in the preoperative and postoperative periods were observed. The levels of C-reactive protein and CAC scores were significantly decreased in the treatment group after treatment. While there was no significant difference in blood calcium, blood phosphorus, PTH, calcium-phosphorus product, and CAC score in the control group after treatment. And after treatment, the proportion of skin pruritus, myasthenia, bone pain, insomnia, restless legs syndrome, and other symptoms in the treatment group was significantly decreased compared with those before treatment, but there was no significant change in the control group before and after treatment. Sodium thiosulfate can reduce the high level of CAC in hemodialysis patients obviously.

The Advances of Neutrophil-Derived Effective Drug Delivery Systems: A Key Review of Managing Tumors and Inflammation.

The chimeric trait of recruitment by inflammatory signals endows neutrophils with the functionality of migrating to inflamed tissues, which can be utilized to tailor novel drug delivery systems. In this review, we introduce a mechanism of neutrophil-derived drug delivery systems recruited into inflamed sites and provide insight into tumors and inflammation therapy. In particular, the advantages of neutrophils-their endogenous-derived neutrophil membrane, exosomes as drug carriers for augmented targeting, prolonged circulation, and improved biostability-were concluded. Subsequently, the latest application in the treatment of tumors and inflammation was elaborated upon, followed by a discussion of the future prospects to neutrophil-derived delivery systems. This promising system will provide new therapeutic avenues for the treatment of inflammation and tumors.

SYDE1 Acts as an Oncogene in Glioma and has Diagnostic and Prognostic Values.

Objectives: Gliomas remain one of serious public health problems worldwide which demand further and deeper investigation. The aim of this study was to explore the association between synapse defective protein 1 homolog 1 (SYDE1) and gliomas via public database analysis and in vitro validation to determine the potential diagnostic and prognostic values. Methods and Results: Compared with healthy brain tissues, there was a significant increase in SYDE1 expression in glioma tissues. Additionally, SYDE1 exhibited higher expression levels in glioma patients with unfavorable clinicopathological factors. In vitro knockdown of SYDE1 in glioma cell lines A172 inhibited their migrative and invasive ability but not the proliferative ability. GO and KEGG pathway analysis of the top 100 genes coexpressed with SYDE1 showed enrichments of tumor-associated terms. Further bioinformatic analysis revealed that the SNHG16/hsa-miR-520e/SYDE1 axis might be involved in glioma development. Conclusions: SYDE1 is expressed at higher levels in gliomas than in healthy brains, and can promote metastasis and invasion but not proliferation of gliomas. Furthermore, SYDE1 has values in the diagnosis and prognosis prediction of gliomas.

The predict value of serum/urocystatin C on acute kidney injury in elderly patients with sepsis.

OBJECTIVE: To evaluate the predict value of serum/urocystatin C in acute kidney injury (AKI) in elderly patients with sepsis. METHODS: A retrospective study was performed and 80 senile patients with sepsis in ** hospital of China was included. According to the diagnosis of AKI, all patients were divided into non-AKI group and AKI group. The clinical characteristics, laboratory and physiological indicators of the two groups were compared. The receiver operating characteristic curve (ROC) was used to analyze the accuracy of the variables, including serum cystatin C, urocystatin C, and serum creatinine, to predict the occurrence of AKI in patients with sepsis. RESULTS: Of the 80 elderly patients with sepsis in China, 29 patients had AKI. Compared with the non-AKI group, patients in the AKI group had higher APACHE II scores, higher SOFA scores, higher procalcitonin, and lower mean arterial pressure (P < 0.05). The levels of serum cystatin C, urocystatin C, and serum creatinine in the AKI group were significantly higher than those in the non-AKI group (P < 0.05), while the difference in intensive care unit (ICU) mortality rate between the two groups was not significantly different (P > 0.05). The ROC curve showed that the area under the curve of serum cystatin C was 0.893, the area under the curve of urocystatin C was 0.898, and the area under the curve of serum creatinine was 0.652. CONCLUSION: Serum cystatin and urocystatin could be used to predict the occurrence of AKI in elderly patients with sepsis.

Statistical and network analysis of 1212 COVID-19 patients in Henan, China.

BACKGROUND: COVID-19 is spreading quickly all over the world. Publicly released data for 1212 COVID-19 patients in Henan of China were analyzed in this paper. METHODS: Various statistical and network analysis methods were employed. RESULTS: We found that COVID-19 patients show gender (55% vs 45%) and age (81% aged between 21 and 60) preferences; possible causes were explored. The estimated average, mode and median incubation periods are 7.4, 4 and 7 days. Incubation periods of 92% of patients were no more than 14 days. The epidemic in Henan has undergone three stages and has shown high correlations with the numbers of patients recently returned from Wuhan. Network analysis revealed that 208 cases were clustering infected, and various People's Hospitals are the main force in treating COVID-19. CONCLUSIONS: The incubation period was statistically estimated, and the proposed state transition diagram can explore the epidemic stages of emerging infectious disease. We suggest that although the quarantine measures are gradually working, strong measures still might be needed for a period of time, since ∼7.45% of patients may have very long incubation periods. Migrant workers or college students are at high risk. State transition diagrams can help us to recognize the time-phased nature of the epidemic. Our investigations have implications for the prevention and control of COVID-19 in other regions of the world.

MiR-424 is over-expressed and attenuates ischemia-reperfusion kidney injury via p53 and death receptor 6 pathway.

BACKGROUND: Ischemic reperfusion injury of kidney is major cause for renal failure, however the involved pathogenesis remains unclear creating an void for its effective treatment. Here we studied involvement of microRNA-424 in renal injury. METHODS: For the study, p53 or HIF-1α mice were used, ischemic renal injury was induced using clamping of renal pedicles bilateraly. Proximal kidney tubular cells were used for in vitro studies. Hoechst 33342 analysis was done for apoptosis. Blood urea nitrogen (BUN) and serum creatinine was done for renal function, Hematoxylin-eosin tissue damage and Terminal transferase-dUTP nick-end labeling assay for apoptosis. RT-PCR was done for miRNA and ChIP assay to identify the binding of p53 to miR-424. TargetScan and miRanda data base were scanned to find targets of miR-424. Protein expression was done by western blot analysis. RESULTS: We discovered that, miR-424 was over-expressed in ischemic renal injury mice and in hypoxia exposed renal cells. In cells, miR-424 suppressed the expression levels of death receptor 6 (DR6) and halted the apoptosis mediated by hypoxia. Blocking of miR-424 halted the inhibition of DR6 and caused apoptosis and activation of caspase. In mice, miR-424 mimic inhibited expression of DR6 and attenuated ischemic renal injury. We established that, up-regulation of miR-424 in ischemic reperfusion injury was p53 dependent, also inhibition of p53 caused repression of miR-424 levels in hypoxia induced cells in vitro. The p53 knockout mice showed attenuation in levels of miR-424 confirming role of p53 behind up-regulation of miR-424 in vivo. CONCLUSION: The study confirmed p53/miR-424/DR6 as a protective cascade during ischemic-reperfusion injury.

Micro RNA-155 inhibitor as a potential therapeutic strategy for the treatment of acute kidney injury (AKI): a nanomedicine perspective.

In this study, we have prepared miR-155 inhibitor-loaded liposome vesicles for the effective treatment of acute kidney injury. The efficacy of liposomal miR-155 inhibitor in the expression of miR-155, mortality in animals, the expression of TNF-α-IL6, and the expression of SOCS1-STAT1 were evaluated. The loading of miR-155 inhibitor into liposomes conferred the much needed colloidal stability and efficient delivery to the renal tissues. The study clearly shows that miR-I-LV significantly decreases the expression of miR-155 in kidneys compared to LPS. Administration of miR-I-LV remarkably reduced the pathological concerns of the kidneys with a marked decrease in inflammatory cell infiltration. Scrambled miR-155 did not have any effect on the expression of these markers; however miR-I-LV showed a remarkable ability to decrease the expression of TNF-α and IL-6 in kidney tissues indicating an ability to treat acute kidney infections. Overall, administration of miR-155 inhibitor effectively alleviated LPS-induced kidney injury by significantly suppressing TNF-α and IL-6 in kidney tissue and by remarkably increasing the expression of mRNA of SOCS1 and STAT1. The present results suggest that miR-155 inhibitor could be used in an effective targeting strategy for the treatment of acute kidney injury (AKI).

Resveratrol attenuates skeletal muscle atrophy induced by chronic kidney disease via MuRF1 signaling pathway.

Skeletal muscle atrophy is an important clinical characteristic of chronic kidney disease (CKD); however, at present, the therapeutic approaches to muscle atrophy induced by CKD are still at an early stage of development. Resveratrol is used to attenuate muscle atrophy in other experimental models, but the effects on a CKD model are largely unknown. Here, we showed that resveratrol prevented an increase in MuRF1 expression and attenuated muscle atrophy in vivo model of CKD. We also found that phosphorylation of NF-κB was inhibited at the same time. Dexamethasone-induced MuRF1 upregulation was significantly attenuated in C2C12 myotubes by resveratrol in vitro, but this effect on C2C12 myotubes was abrogated by a knockdown of NF-κB, suggesting that the beneficial effect of resveratrol was NF-κB dependent. Our findings provide novel information about the ability of resveratrol to prevent or treat muscle atrophy induced by CKD.