Immune checkpoint inhibitors and acute kidney injury

As a new type of anti-tumor immunotherapy, immune checkpoint inhibitors (ICIs) have improved the prognosis of multiple malignancies. However, renal complications are becoming more frequent. Nephrotoxicity often manifests as acute kidney injury (AKI), and the most common histopathological type is acute tubulointerstitial nephritis (ATIN). Based on previous studies of the incidence and potential risk factors for nephrotoxicity, in this review, we describe the mechanism of AKI after ICIs treatment, summarize the incidence, risk factors, and outcomes of AKI, and discuss the diagnosis and management of immune checkpoint inhibitors-associated acute kidney injury (ICI-AKI). In addition, we review the current status of ICIs rechallenge and the therapeutic strategies of ICIs applied in kidney transplant recipients. Finally, we emphasize the importance of collaboration between nephrologists and oncologists to guide the treatment of ICIs and the management of renal complications

TFRC upregulation promotes ferroptosis in CVB3 infection via nucleus recruitment of Sp1

Abstract CVB3 is a single positive-strand enterovirus, and a common pathogen in myocarditis etiology. Although a number of antiviral candidates are under development, specific targeted therapy is not available for CVB3. Ferroptosis is a new type of regulatory cell death discovered in recent years. In this study, our team provided the first evidence that ferroptosis existed in CVB3 infection in vivo and in vitro by iron overload, and massive accumulation of lipid peroxides. Mechanistically, we construct a classical model of HeLa cells following a time-course infection (6, 12, 24, 36, 48 h) with CVB3 (MOI = 10). We demonstrated that the TFRC gene plays an important role in promoting ferroptosis in CVB3 infection and downregulation of TFRC attenuated the ferroptosis. Interestingly, we observed that TFRC was nuclear translocation induced by the CVB3, which was predominantly localized in the cell membrane, but redistributed to the nucleus during CVB3 infection. Moreover, we found that the transcription factor Sp1 was an essential factor that could bind to the TFRC promoter and upregulate the TFRC transcription. Collectively, these results suggest that the Sp1/TFRC/Fe axis may provide a new target for the development of therapies against CVB3 infection

The RCC 1 family protein SAB 1 negatively regulates ABI 5 through multidimensional mechanisms during postgermination in Arabidopsis

Abscisic acid-insensitive 5 (ABI5) is an essential and conserved plant basic leucine zipper transcription factor whose level controls seed germination and postgerminative development. It has been demonstrated that activity of ABI5 is transcriptionally and post-translationally regulated. However, transcriptional regulation of ABI5 is not fully understood. Here, we identified SAB1 (Sensitive to ABA 1) as a novel negative regulator of ABI5 that simultaneously regulates its stability, promoter binding activity and histone methylationmediated gene silencing of ABI5. SAB1 encodes a Regulator of Chromatin Condensation 1 (RCC1) family protein and is expressed in an opposite pattern to that of ABI5 during early seedling growth in response to abscisic acid (ABA). SAB1 mutation results in enhanced ABA sensitivity and acts upstream of ABI5. SAB1 physically interacts with ABI5 at phosphoamino acid Ser-145, and reduces the phosphorylation of ABI5 and the protein stability. SAB1 reduces ABI5 binding activity to its own promoter, leading to reduced transcriptional level of ABI5. SAB1 inactivates ABI5 transcription by increasing the level of histone H3K27me2 in the ABI5 promoter. Our findings have identified SAB1 as a crucial new component of ABA signaling which modulates early development of plant by precisely controlling ABI5 activity through multiple mechanisms

Dietary Addition of Antioxidant Complex Packs and Functional Amino Acids Can Improve the Digestion, Absorption, and Immunity of Huanjiang Minipigs

To study the effect of functional amino acids and the antioxidant function compound package on Huanjiang minipigs and to lay a foundation for the formulation of green and efficient feed for Huanjiang minipigs, we added functional amino acids and the antioxidant function compound package to piglet feed for 28 days. After feeding, we detected the growth performance, biochemical indexes, inflammatory indexes, and intestinal disaccharidase of piglets. It was found that functional amino acids and the antioxidant compound package had certain effects on the growth performance and biochemical indexes of piglets and could reduce the level of IL-6 and increase the level of LZM and SIgA of piglets, and the levels of lactase and maltase in the intestine also increased significantly. The results showed that the compound package of functional amino acids and antioxidation could improve the growth performance and immunity of piglets and promote the digestion and absorption of nutrients in piglets

Fatty Acid Synthase Mutations Predict Favorable Immune Checkpoint Inhibitor Outcome and Response in Melanoma and Non-Small Cell Lung Cancer Patients

Fatty acid synthase (FASN) acts as the central member in fatty acid synthesis and metabolism processes, which regulate oncogenic signals and tumor immunogenicity. To date, no studies have reported the connection of FASN mutations with ICI efficacy. In this study, from 631 melanoma and 109 NSCLC patients who received ICI treatments, we retrospectively curated multiomics profiles and ICI treatment data. We also explored the potential molecular biological mechanisms behind FASN alterations. In melanoma patients, FASN mutations were observed to associate with a preferable immunotherapeutic prognosis and response rate (both p p FASN mutations. This work confirms the clinical immunotherapy implications of FASN mutation-mediated fatty acid metabolism and provides a possible indicator for immunotherapy prognosis prediction

N6-methyladenosine methylation in kidney injury

Abstract Multiple mechanisms are involved in kidney damage, among which the role of epigenetic modifications in the occurrence and development of kidney diseases is constantly being revealed. However, N6-methyladenosine (M6A), a well-known post-transcriptional modification, has been regarded as the most prevalent epigenetic modifications in higher eukaryotic, which is involved in various biological processes of cells such as maintaining the stability of mRNA. The role of M6A modification in the mechanism of kidney damage has attracted widespread attention. In this review, we mainly summarize the role of M6A modification in the progression of kidney diseases from the following aspects: the regulatory pattern of N6-methyladenosine, the critical roles of N6-methyladenosine in chronic kidney disease, acute kidney injury and renal cell carcinoma, and then reveal its potential significance in the diagnosis and treatment of various kidney diseases. A better understanding of this field will be helpful for future research and clinical treatment of kidney diseases

<i>HSPG2</i> Mutation Association with Immune Checkpoint Inhibitor Outcome in Melanoma and Non-Small Cell Lung Cancer

Immune checkpoint inhibitors (ICIs) markedly promote the survival outcome of advanced melanoma and non-small cell lung cancer (NSCLC). Clinically, favorable ICI treatment efficacy is noticed only in a smaller proportion of patients. Heparan sulfate proteoglycan 2 (HSPG2) frequently mutates in both tumors. Herein, we aim to investigate the immunotherapeutic and immunological roles of HSPG2 mutations in melanoma and NSCLC. A total of 631 melanoma samples and 109 NSCLC samples with both somatic mutational profiles and clinical immunotherapy data were curated. In addition, by using The Cancer Genome Atlas data, genomic and immunological traits behind HSPG2 mutations were elucidated. Melanoma patients with HSPG2 mutations had a markedly extended ICI outcome than other patients. An association between HSPG2 mutations and the improved outcome was further confirmed in NSCLC. In addition, an elevated ICI response rate was presented in HSPG2-mutated NSCLC patients (81.8% vs. 29.7%, p = 0.002). Subsequent analyses revealed that HSPG2-mutated patients had a favorable abundance of response immunocytes, an inferior abundance of suppression immunocytes, enhanced mutational burden, and interferon response-relevant signaling pathways. We uncovered that HSPG2 mutations were predictive of a better ICI response and associated with preferable immunogenicity, which may be considered as a genomic determinant to customize biotherapy strategies

Table_1_Positive effect of Balint group on burnout and self-efficacy of head nurses in China: a randomized controlled trial.XLSX

BackgroundBurnout is common among nurses and can lead to negative outcomes of medical care. This study aimed to explore the effectiveness of Balint groups to reduce burnout in head nurses in a Chinese hospital.MethodsThis was a randomized controlled trial with a pre- and post-test. A total of 80 head nurses were randomly assigned to either a Balint group (n = 40) or a control group (n = 40). Participants participated in Balint group for a period of 3 months. Participants in both groups completed the Maslach Burnout Inventory-Human Services Survey and the General Self-Efficacy Scale at the beginning and end of the study. Balint group members also completed the Group Climate Questionnaire-Short Form.ResultsIn the Balint group, 33 participants attended all Balint groups, while the 40 participants in the control group had no intervention. Analysis of variance with repeated measures demonstrated a statistically significant difference on the Maslach Burnout Inventory subscale of sense of personal achievement (F = 9.598, p = 0.003) between the Balint and control groups. However, there were no significant differences between the groups on the subscales of emotional exhaustion (F = 0.110, p = 0.740) and depersonalization (F = 0.75, p = 0.387), and the General Self-Efficacy Scale (F = 0.709, p = 0.403).ConclusionsBalint groups helped reduce burnout among head nurses in terms of personal achievement.</p