Effects of Oxygen Therapy on Patients with a Chronic Wound: A Systematic Review and Meta-analysis.

OBJECTIVE: To synthesize the effects of oxygen-based therapy on patients with a chronic wound. DATA SOURCES: The authors searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials for relevant randomized controlled trials from database inception. Investigators measured risk of bias using the Cochrane Collaboration's Risk of Bias tool. STUDY SELECTION: The included randomized controlled trials focused on the effects (short- or long-term wound healing, amputation rate, percentage of reduction in ulcer size, and poststudy transcutaneous oxygen measurement [TcPO2]) of oxygen-based therapy (including hyperbaric oxygen therapy, topical oxygen therapy, and continuous diffusion of oxygen) on patients with a chronic wound. DATA EXTRACTION: Researchers extracted information regarding participant characteristics and primary and secondary outcomes from the included studies. DATA SYNTHESIS: Pooled effects of 31 included studies showed that patients treated with oxygen had better short-term wound healing (risk ratio [RR], 1.544; 95% CI, 1.199 to 1.987), a higher percentage reduction in the ulcer area (standardized mean difference [SMD], 0.999; 95% CI, 0.439 to 1. 599), lower amputation rates (RR, 0.529; 95% CI, 0.325 to 0.862), shorter wound healing time (SMD, -0.705; 95% CI, -0.908 to -0.501), and higher poststudy TcPO2 (SMD, 2.128; 95% CI, 0.978 to 3.278) than those in the control group. For long-term wound healing, there was no statistically significant difference (RR, 1.227; 95% CI, 0.976 to 1.542). CONCLUSIONS: Oxygen-based therapy improves short-term parameters of wound healing in patients with chronic wounds.

Bioequivalue of two mycophenolate sodium enteric-coated tablets and the drug monitoring based on limited sampling strategy: A single-center, randomized, open-label, three-period, reference-replicated, crossover study.

OBJECTIVE: A mycophenolate sodium enteric-coated tablet has shown a satisfying anti-rejection effect in patients receiving solid organ transplantation. The current study evaluated the bioequivalence between the test (Ruiyirong®) vs. reference (Myfortic®) formulations by exploring equations for predicting their area under the concentration-time curve (AUC) using a limited sampling strategy in healthy subjects. METHODS: Forty-eight healthy Chinese subjects were randomized into three administration sequences (test-reference-reference, reference-reference-test, and reference-test-reference) to receive the Ruiyirong or Myfortic treatment on days 1, 8, and 15. RESULTS: The 90% confidential interval (CI) of the geometric mean ratios (test/reference) of maximum plasma concentration (Cmax), the AUC from time 0 to the last timepoint (AUC0-t), and the AUC from 0 to infinity (AUC0-∞) was 92.90%-110.57%, 96.91%- 101.80%, and 96.71%-101.84%, respectively. All these values fell into the bioequivalence criteria of 80.00%-125.00% (based on the criteria of the Food and Drug Administration). The adverse events were 10.4% in Ruiyirong test group and 14.6% in Myfortic reference group. Eight equations for estimating the AUC of the Ruiyirong test and Myfortic reference formulations were evaluated; most of them worked well with the R-value >0.8. Among the four chosen equations, the intragroup verification exhibited a high agreement with the R-value ranging from 0.857 to 0.971 and with the low predictive error (PE > 5% with absolute PE > 15%). Meanwhile, the intergroup verification indicated a high inter-agreement with the R-value ranging from 0.896 to 0.974 (all P < 0.001). CONCLUSION: The Ruiyirong test vs. Myfortic reference formulations meet the bioequivalent criteria and are well tolerated. The further linear regression analysis explores eight equations predicting the AUC value and the chosen four equations for the Ruiyirong test and Mayfortic reference formulations are interchangeable.

Analysis of risk factors and establishment of a risk prediction model for post-transplant diabetes mellitus after kidney transplantation.

Introduction: Post-transplant diabetes mellitus (PTDM) is a known side effect in transplant recipients administered immunosuppressant drugs, such as tacrolimus. This study aimed to investigate the risk factors related to PTDM, and establish a risk prediction model for PTDM. In addition, we explored the effect of PTDM on the graft survival rate of kidney transplantation recipients. Methods: Patients with pre-diabetes mellitus before kidney transplant were excluded, and 495 kidney transplant recipients were included in our study, who were assigned to the non-PTDM and PTDM groups. The cumulative incidence was calculated at 3 months, 6 months, 1 year, 2 years, and 3 years post-transplantation. Laboratory tests were performed and the tacrolimus concentration, clinical prognosis, and adverse reactions were analyzed. Furthermore, binary logistic regression analysis was used to identify the independent risk factors of PTDM. Results: Age ≥ 45 years (adjusted odds ratio [aOR] 2.25, 95% confidence interval [CI] 1.14-3.92; P = 0.015), body mass index (BMI) > 25 kg/m2 (aOR 3.12, 95% CI 2.29-5.43, P < 0.001), tacrolimus concentration > 10 ng/mL during the first 3 months post-transplantation (aOR 2.46, 95%CI 1.41-7.38; P < 0.001), transient hyperglycemia (aOR 4.53, 95% CI 1.86-8.03; P < 0.001), delayed graft function (DGF) (aOR 1.31, 95% CI 1.05-2.39; P = 0.019) and acute rejection (aOR 2.16, 95% CI 1.79-4.69; P = 0.005) were identified as independent risk factors of PTDM. The PTDM risk prediction model was developed by including the above six risk factors, and the area under the receiver operating characteristic curve was 0.916 (95% CI 0.862-0.954, P < 0.001). Furthermore, the cumulative graft survival rate was significantly higher in the non- PTDM group than in the PTDM group. Conclusions: Risk factors related to PTDM were age ≥ 45 years, BMI > 25 kg/m2, tacrolimus concentration > 10 ng/mL during the first 3 months post-transplantation, transient hyperglycemia, DGF and acute rejection.

Tacrolimus Concentration Is Effectively Predicted Using Combined Clinical and Genetic Factors in the Perioperative Period of Kidney Transplantation and Associated with Acute Rejection.

Background: Tacrolimus has unpredictable pharmacokinetic (PK) characteristics, which are partially attributed to CYP3A5 polymorphism. The potential effects of clinical factors in the postoperative period of transplantation on tacrolimus PK and those of early tacrolimus PK variability on clinical outcomes are yet to be clarified. Methods: We examined the genetic and clinical factors affecting early tacrolimus PK variability in 256 kidney transplant recipients. The relationships among tacrolimus exposure, graft function delay (DGF), and acute rejection (AR) were further explored. Findings. The CYP3A5 genotype were strongly associated with tacrolimus concentration/dose ratio (C 0/D). Additionally, ABCB1 (rs1045642 and rs2032582) and ABCC2 (rs3740066) were found to have potential independent effects on early tacrolimus C 0/D in multivariate analysis. Red blood counts and albumin level were the most significant clinical factors associated with tacrolimus C 0/D. Wuzhi capsule also exerted an effect on tacrolimus PK. A model combined with pharmacogenetic and clinical factors explained 43.4% tacrolimus PK variability compared with 16.3% on the basis of CYP3A5 genotype only. Notably, increasing tacrolimus concentrations in the early postoperative stage were associated with AR, but not DGF. Conclusions: Combined analysis of genotype and specific clinical factors is important for the formulation of precise tacrolimus dose regimens in the early stage after kidney transplantation.

Retrospective Analysis of the Risk Factors of Perioperative Bacterial Infection and Correlation with Clinical Prognosis in Kidney Transplant Recipients.

Background: Infection remains a leading cause of morbidity and mortality in kidney transplant patients. This study aimed to investigate the risk factors of bacterial infection during the perioperative period of transplantation and the effects of infection on long-term clinical outcomes. Methods: In total, 295 kidney transplantation recipients were included in this retrospective study and assigned to two groups: non-infected and infected. The tacrolimus concentration, pharmacogenomics, laboratory parameters, and clinical outcomes of both groups were evaluated. Results: A relatively low incidence of urinary tract infection was observed in our cohort, and lung was identified as the most frequent site of infection. Gram-negative bacteria, such as Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae, were the most common infecting strains in kidney transplant recipients. Patients with diabetes showed greater susceptibility to infection. Compared with the non-infected group, tacrolimus concentration was significantly lower on day 7 and 14 in the infected group. White blood cell count, neutrophil count, and C-reactive protein (CRP) in the infected group were markedly higher post-transplantation, while albumin levels were lower relative to the non-infected group. ABCB1 (rs2032582) genotype showed clear associations with infection. Furthermore, the incidence of delayed graft function (DGF) and early acute rejection (AR) before infection was significantly greater in the infected group. Finally, early post-transplant infection was associated with a marked increase in the incidence of AR, post-transplant diabetes mellitus (PTDM), and secondary infection. Conclusion: Pre-diabetes, longer duration of catheterization, lower albumin, higher CRP, tacrolimus concentration on the day 7 and 14, early AR before infection, and DGF were closely related to postoperative infection in kidney transplantation recipients. Moreover, bacterial infection during the perioperative period was closely associated with AR, PTDM and secondary infection.

Effect of primary and secondary Fasciola gigantica infection on specific IgG responses, hepatic enzyme levels and weight gain in buffaloes.

Buffaloes, as highly susceptible definitive hosts of Fasciola gigantica, suffer from a high infection rate of fasciolosis, which causes enormous economic losses. Repeat infection is responsible for this high rate; thus, elucidating the protective immunity mechanism in repeat infection is decisive in fasciolosis prevention. Herein, a secondary experimental infection model was established to preliminarily reveal the protective immunity that occurs in repeat infection. In brief, animals were assigned to three groups: group A (uninfected control), group B (primary infection) and group C (secondary infection). Buffaloes were autopsied 20 weeks post-infection for measurements of the recovered flukes and hepatic examination. In addition, the detection of specific antibody (IgG) responses to F. gigantica excretory-secretory product (FgESP) throughout the whole period and weight gain throughout the first 4 months as a percentage (%) of the starting weight were also determined. The serum hepatic enzyme gamma glutathione transferase (GGT) levels were monitored to assess hepatic damage throughout the study period. Infection establishment was compared between group B and group C. Similar specific IgG patterns were observed between group B and group C, and hepatic damage was more severe in group C than group B. Significant differences in weight gain as a percentage of the start weight were observed between group A and group B at the 3rd and 4th months postprimary infection, while significant differences were not observed between group A and group C or group B and group C. Our results suggest that challenge infection cannot induce resistance against F. gigantica in buffaloes, which is consistent with the protective immunity against Fasciola hepatica reinfection observed in sheep and goats.

The Effects of Oral Sodium Bicarbonate on Renal Function and Cardiovascular Risk in Patients with Chronic Kidney Disease: A Systematic Review and Meta-Analysis.

OBJECTIVE: Oral sodium bicarbonate is often used to correct acid-base disturbance in patients with chronic kidney disease (CKD). However, there is little evidence on patient-level benign outcomes to support the practice. METHODS: We conducted a systematic review and meta-analysis to examine the efficacy and safety of oral sodium bicarbonate in CKD patients. A total of 1853 patients with chronic metabolic acidosis or those with low-normal serum bicarbonate (22-24 mEq/L) were performed to compare the efficacy and safety of oral sodium bicarbonate in patients with CKD. RESULTS: There was a significant increase in serum bicarbonate level (MD 2.37 mEq/L; 95% CI, 1.03 to 3.72) and slowed the decline in estimated glomerular filtration rate (eGFR) (MD -4.44 mL/min per 1.73 m2, 95% CI, -4.92 to -3.96) compared with the control groups. The sodium bicarbonate lowered T50-time, an indicator of vascular calcification (MD -20.74 min; 95% CI, -49.55 to 8.08); however, there was no significant difference between the two groups. In addition, oral sodium bicarbonate dramatically reduced systolic blood pressure (MD -2.97 mmHg; 95% CI, -5.04 to -0.90) and diastolic blood pressure (MD -1.26 mmHg; 95% CI, -2.33 to -0.19). There were no statistically significant body weight, urine pH and mean mid-arm muscle circumference. CONCLUSION: Treatment of metabolic acidosis with sodium bicarbonate may slow the decline rate of kidney function and potentially significantly improve vascular endothelial function in patients with CKD. PROSPERO REGISTRATION NUMBER: CRD42020207185.

Genetic Polymorphisms Affecting Tacrolimus Metabolism and the Relationship to Post-Transplant Outcomes in Kidney Transplant Recipients.

BACKGROUND: Tacrolimus is a key drug in kidney transplantation with a narrow therapeutic index. However, whether tacrolimus exposure variability affects clinical outcomes and adverse reactions remains unknown. OBJECTIVE: Our study investigated the factors that influence tacrolimus exposure in kidney transplantation recipients and the relationship between tacrolimus concentration and clinical outcomes and adverse reactions. SETTINGS AND METHODS: We examined the effect of tacrolimus concentration on clinical outcomes and adverse reactions in 201 kidney transplantation recipients, and identified clinical and pharmacogenetic factors that explain tacrolimus exposure. RESULTS: The CYP3A5 genotype was clearly associated with dose-adjusted trough blood tacrolimus concentrations (C0/D), whereas no significant difference was observed in patients with the CYP3A4*1B, CYP3A4*22, ABCB1, ABCC2, POR*28 or PXR alleles. Clinical factors such as red blood cell count, hemoglobin, and albumin were the most useful influence factors affecting tacrolimus C0/D. Besides, Wuzhi capsule increased tacrolimus C0/D in kidney transplantation recipients. Furthermore, higher tacrolimus concentrations were associated with higher diarrhea and post-transplant diabetes mellitus (PTDM) risk but not with acute rejection and chronic allograft kidney dysfunction. CONCLUSION: Clinical factors, medication, and CYP-enzyme polymorphisms accounted for tacrolimus concentration variability in kidney transplantation recipients. Furthermore, higher tacrolimus concentrations were associated with higher diarrhea and PTDM risk.

The roles of NFE2L1 in adipocytes: Structural and mechanistic insight from cell and mouse models.

Adipocytes play pivotal roles in maintaining energy homeostasis by storing lipids in adipose tissue (AT), regulating the flux of lipids between AT and the circulation in response to the body's energy requirements and secreting a variety of hormones, cytokines and other factors. Proper AT development and function ensure overall metabolic health. Nuclear factor erythroid 2-related factor 1 (NFE2L1, also known as NRF1) belongs to the CNC-bZIP family and plays critical roles in regulating a wide range of essential cellular functions and varies stress responses in many cells and tissues. Human and rodent Nfe2l1 genes can be transcribed into multiple splice variants resulting in various protein isoforms, which may be further modified by a variety of post-translational mechanisms. While the long isoforms of NFE2L1 have been established as master regulators of cellular adaptive antioxidant response and proteasome homeostasis, the exact tissue distribution and physiological function of NFE2L1 isoforms, the short isoforms in particular, are still under intense investigation. With regard to key roles of NFE2L1 in adipocytes, emerging data indicates that deficiency of Nfe2l1 results in aberrant adipogenesis and impaired AT functioning. Intriguingly, a single nucleotide polymorphism (SNP) of the human NFE2L1 gene is associated with obesity. In this review, we summarize the most significant findings regarding the specific roles of the multiple isoforms of NFE2L1 in AT formation and function. We highlight that NFE2L1 plays a fundamental regulatory role in the expression of multiple genes that are crucial to AT metabolism and function and thus could be an important target to improve disease states involving aberrant adipose plasticity and lipid homeostasis.

CL316243 treatment mitigates the inflammation in white adipose tissues of juvenile adipocyte-specific Nfe2l1 knockout mice.

Nuclear factor-erythroid 2-related factor 1 (NFE2L1) is a key transcription factor that regulates cellular adaptive responses to various stresses. Our previous studies revealed that adult adipocyte-specific Nfe2l1-knockout [Nfe2l1(f)-KO] mice show adipocyte hypertrophy and severe adipose inflammation, which can be worsened by rosiglitazone, a peroxisome proliferator-activated receptor γ agonist. To further assess the crucial roles of NFE2L1 in adipocytes, we investigated the effect of CL316243, a ß3 adrenergic agonist that promotes lipolysis via a post-translational mechanism, on adipose inflammation in juvenile Nfe2l1(f)-KO mice. In contrast to adult mice, 4-week-old juvenile Nfe2l1(f)-KO mice displayed a normal fat distribution but reduced fasting plasma glycerol levels and elevated adipocyte hypertrophy and macrophage infiltration in inguinal and gonadal WAT. In addition, Nfe2l1(f)-KO mice had decreased expression of multiple lipolytic genes and reduced lipolytic activity in WAT. While 7 days of CL316243 treatment showed no significant effect on adipose inflammation in Nfe2l1-Floxed control mice, the same treatment dramatically alleviated macrophage infiltration and mRNA expression of inflammation and pyroptosis-related genes in WAT of Nfe2l1(f)-KO mice. Together with previous findings in adult mice, the current study highlights that NFE2L1 plays a fundamental regulatory role in lipolytic gene expression and thus might be an important target to improve adipose plasticity and lipid homeostasis.

Rifampicin impairs adipogenesis by suppressing NRF2-ARE activity in mice fed a high-fat diet.

Prolonged treatment with rifampicin (RFP), a first-line antibacterial agent used in the treatment of drug-sensitive tuberculosis, may cause various side effects, including metabolic disorders. The nuclear factor (erythroid-derived 2)-like 2 (NFE2L2, also known as NRF2) plays an essential regulatory role in cellular adaptive responses to stresses via the antioxidant response element (ARE). Our previous studies discovered that NRF2 regulates the expression of CCAAT-enhancer-binding protein ß (Cebpb) and peroxisome proliferator-activated receptor gamma (Pparg) in the process of adipogenesis. Here, we found that prolonged RFP treatment in adult male mice fed a high-fat diet developed insulin resistance, but reduced fat accumulation and decreased expression of multiple adipogenic genes in white adipose tissues. In 3 T3-L1 preadipocytes, RFP reduced the induction of Cebpb, Pparg and Cebpa at mRNA and protein levels in the early and/or later stage of hormonal cocktail-induced adipogenesis. Mechanistic investigations demonstrated that RFP inhibits NRF2-ARE luciferase reporter activity and expression of NRF2 downstream genes under normal culture condition and in the early stage of adipogenesis in 3 T3-L1 preadipocytes, suggesting that RFP can disturb adipogenic differentiation via NRF2-ARE interference. Taken together, we demonstrate a potential mechanism that RFP impairs adipose function by which RFP likely inhibits NRF2-ARE pathway and thereby interrupts its downstream adipogenic transcription network.

Diagnostic Accuracy of Donor-derived Cell-free DNA in Renal-allograft Rejection: A Meta-analysis.

BACKGROUND: Donor-derived cell-free DNA (dd-cfDNA) is a potential noninvasive molecular marker of graft rejection after kidney transplant, whose diagnostic accuracy remains controversial. METHODS: We performed a systematic review and metaanalysis to evaluate the diagnostic accuracy of dd-cfDNA. Relevant literature was searched from online databases, and the data on the diagnostic accuracy of discriminating main rejection episodes (MRE) and antibody-mediated rejection (AMR) were merged, respectively. RESULTS: Nine studies were included in the metaanalysis, of which 6 were focused on the diagnostic accuracy of dd-cfDNA for MRE, whose pooled sensitivity, specificity, area under the receiver operating characteristics curve, diagnostic odds ratio, overall positive likelihood ratio, and negative likelihood ratio with 95% confidence intervals were 0.70 (0.57-0.81), 0.78 (0.70-0.84), 0.81 (0.77-0.84), 8.18 (5.11-13.09), 3.15 (2.47-4.02), and 0.39 (0.27-0.55), respectively. Five tests were focused on discriminating AMR, whose pooled indicators were 0.84 (0.75-0.90), 0.80 (0.74-0.84), 0.89 (0.86-0.91), 20.48 (10.76-38.99), 4.13(3.21-5.33), and 0.20(0.12-0.33), respectively. CONCLUSIONS: Donor-derived cell-free DNA can be a helpful marker for the diagnosis of AMR among those recipients suspected of renal dysfunction. Its diagnostic accuracy on the MRE remains uncertain, which requires further prospective, large-scale, multicenter, and common population research.

Reconstruction of a Transplant Recipient's External Iliac Artery Using Donor's Inferior Vena Cava in Renal Transplantation: 2 Case Reports.

Iliac atherosclerosis is common in renal transplant recipients. In severe cases, it affects intraoperative renal arterial anastomosis and increases the risk of postanastomosis complications. At present, safe and efficient vascular replacement methods are relatively limited. In the 2 renal transplant cases at our center, described here, the donors' iliac arteries were unavailable. We therefore attempted to replace the recipients' diseased external iliac artery with the donors' inferior vena cava and then performed an end-to-side grafting with the attachment in arterial reconstruction. One patient received a single kidney transplantation, while the other received a dual kidney transplantation. Antiplatelet/anticoagulation drug application was avoided, and both patients were observed for more than 6 months. Stable renal graft function was achieved without any vascular complications. During this study, all procedures were in compliance with the Helsinki Congress and the Declaration of Istanbul. For end-stage renal disease patients with severe iliac atherosclerosis who are waiting for kidney transplantation, a donor's vena cava graft could potentially be a promising replacement option to restore external iliac artery patency and reconstruct renal blood flow, without the necessity of harvesting a recipient's autologous vessels or looking for costly artificial ones.

Identification of Kidney Transplant Recipients with Coronavirus Disease 2019.

Coronavirus disease 2019 (COVID-19) is a novel and lethal infectious disease, posing a threat to global health security. The number of cases has increased rapidly, but no data concerning kidney transplant (KTx) recipients infected with COVID-19 are available. To present the epidemiological, clinical, and therapeutic characteristics of KTx recipients infected with COVID-19, we report on a case series of five patients who were confirmed as having COVID-19 through nucleic acid testing (NAT) from January 1, 2020 to February 28, 2020. The most common symptoms on admission to hospital were fever (five patients, 100%), cough (five patients, 100%), myalgia or fatigue (three patients, 60%), and sputum production (three patients, 60%); serum creatinine or urea nitrogen levels were slightly higher than those before symptom onset. Four patients received a reduced dose of maintenance immunosuppressive therapy during hospitalization. As of March 4, 2020 NAT was negative for COVID-19 in three patients twice in succession, and their computed tomography scans showed improved images. Although greater patient numbers and long-term follow-up data are needed, our series demonstrates that mild COVID-19 infection in KTx recipients can be managed using symptomatic support therapy combined with adjusted maintenance immunosuppressive therapy.

Nrf2 in adipocytes.

White adipocytes play a key role in maintaining whole body energy homeostasis by forming white adipose tissue (WAT). The impairment of WAT formation or WAT dysfunction is clearly associated with severe metabolic disorders. Mature adipocytes are derived from differentiated preadipocytes and are pivotal in energy storage and metabolism. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a member of a family of CNC-bZIP proteins which exert their transcriptional control on genes harboring antioxidant response elements (ARE) in partnership with small musculoaponeurotic fibrosarcoma proteins. The activation of Nrf2-ARE coordinated by specific repressor Kelch-like ECH-associated protein 1 (Keap1) regulates networks of genes controlling diverse homeostatic processes involving adaptive antioxidant response and detoxification among many other adaptive responses. Interestingly, accumulating evidence indicates that Nrf2 may act as a transcription factor in regulating the formation and function of adipose tissues, including adipogenesis, lipid metabolism and insulin sensitivity. In this mini-review, an overview on the distinct roles of Nrf2 in adipocytes is provided. While highlighting the regulatory role of Nrf2 in adipogenesis, recent key findings on Nrf2 in insulin signal transduction and energy metabolism of adipocytes are also summarized.

Long isoforms of NRF1 negatively regulate adipogenesis via suppression of PPARγ expression.

Nuclear factor erythroid 2-related factor 1 (NRF1), a ubiquitously expressed CNC-bZIP transcription factor, plays a critical role in white adipocyte (WAC) biology, whereas the underlying mechanisms remain unknown. The mouse Nrf1 gene is transcribed in a number of alternatively spliced forms, resulting in two long protein isoforms (L-NRF1) containing 741 and 742 amino acids (aa) and multiple short isoforms (S-NRF1). Our previous study found that adipocyte-specific knockout of Nrf1 [Nrf1(f)-KO] in mice disturbs the expression of lipolytic genes in adipocytes, leading to adipocyte hypertrophy followed by inflammation, pyroptosis and insulin resistance. In the present study, we found that the stromal vascular fraction (SVF) cells isolated from white adipose tissues (WAT) of Nrf1(f)-KO mice display augmented adipogenesis showing elevated mRNA and protein expression of adipogenic markers and lipid accumulation. In 3T3-L1 cells, stable knockdown (KD) of all or long isoforms of Nrf1 (termed as A-Nrf1-KD and L-Nrf1-KD, respectively) using lentiviral shRNAs resulted in enhanced and accelerated adipogenic differentiation. Conversely, overexpression of L-NRF1-741, but not any of the S-NRF1, substantially attenuated adipogenesis in 3T3-L1 cells. These findings indicate that L-NRF1 might serve as a critical negative regulator of adipogenesis. Mechanistic investigation revealed that L-NRF1 may negatively regulates the transcription of peroxisome proliferator-activated receptor γ (PPARγ), in particular the master regulator of adipogenesis PPARγ2. Taken all together, the findings in the present study provide further evidence for a novel role of NRF1 beyond its participation in cellular antioxidant response and suggest that L-NRF1 is a negative regulator of PPARγ2 expression and thereby can suppress adipogenesis.

CircNR3C1 inhibits proliferation of bladder cancer cells by sponging miR-27a-3p and downregulating cyclin D1 expression.

Accumulating evidences suggest that circular RNAs play vital roles in human cancers. Previously, we found that circHIPK3 suppressed invasion of bladder cancer cells via sponging miR-558 and downregulating heparanase expression. In this study, we discovered that a circular RNA derived from NR3C1 (circNR3C1) was downregulated in bladder cancer tissues and cell lines according to RNA-Seq data and qRT-PCR analysis. Functionally, we found that overexpression of circNR3C1 could significantly inhibit cell cycle progression and proliferation of bladder cancer cells in vitro, as well as suppress tumor growth in vivo. Mechanistically, we demonstrated that circNR3C1 possessed four targeting sites of miR-27a-3p and could effectively sponge miR-27a-3p to suppress the expression of cyclin D1. Furthermore, we revealed that miR-27a-3p functioned as an oncogene through interacting with 5'UTR of cyclin D1 to enhance its expression, which led to promote cell cycle progression and proliferation in bladder cancer cells. Conclusively, our findings further confirm the hypothesis that circRNAs function as "microRNA sponges", and our data suggest that circNR3C1 and miR-27a-3p would be potential therapeutic targets for bladder cancer treatment.