Ferroptosis-related genes, a novel therapeutic target for focal segmental glomerulosclerosis.

Recent studies have suggested that ferroptosis participates in various renal diseases. However, its effect on focal segmental glomerulosclerosis remains unclear. This study analyzed the GSE125779 and GSE121211 datasets to identify the differentially expressed genes (DEGs) in renal tubular samples with and without FSGS. The Cytoscape was used to construct the protein-protein interaction network. Moreover, the ferroptosis-related genes (FRGs) were obtained from the ferroptosis database, while ferroptosis-related DEGs were obtained by intersection with DEGs. The target genes were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The GSE108112 dataset was used to verify the expression of target FRGs. Besides, we built the mRNA-miRNA network regarding FRGs using the NetworkAnalyst database, and circRNAs corresponding to key miRNAs were predicted in the ENCORI database. In this study, 16 ferroptosis-related DEGs were identified between FSGS and healthy subjects, while five co-expressed genes were obtained by three topological algorithms in Cytoscape. These included the most concerned Hub genes JUN, HIF1A, ALB, DUSP1 and ATF3. The KEGG enrichment analysis indicated that FRGs were associated with mitophagy, renal cell carcinoma, and metabolic pathways. Simultaneously, the co-expressed hub genes were analyzed to construct the mRNA-miRNA interaction network and important miRNAs such as hsa-mir-155-5p, hsa-mir-1-3p, and hsa-mir-124-3p were obtained. Finally, 75 drugs targeting 54 important circRNAs and FRGs were predicted. This study identified the Hub FRGs and transcriptomic molecules from FSGS in renal tubules, thus providing novel diagnostic and therapeutic targets for FSGS.

Common Key Genes in Differentiating Parathyroid Adenoma From Thyroid Adenoma.

Recent studies have demonstrated the close relationship between parathyroid adenoma (PA) and thyroid follicular adenoma (FTA). However, the underlying pathogenesis remains unknown. This study focused on exploring common pathogenic genes, as well as the pathogenesis of these two diseases, through bioinformatics methods. This work obtained PA and FTA datasets from the Integrated Gene Expression Database to identify the common differentially expressed genes (DEGs) of two diseases. The functions of the genes were investigated by GO and KEGG enrichment. The program CytoHubba was used to select the hub genes, while receiver operating characteristic curves were plotted to evaluate the predictive significance of the hub genes. The DGIbd database was used to identify gene-targeted drugs. This work detected a total of 77 DEGs. Enrichment analysis demonstrated that DEGs had activities of 3',5'-cyclic AMP, and nucleotide phosphodiesterases and were associated with cell proliferation. NOS1, VWF, TGFBR2, CAV1, and MAPK1 were identified as hub genes after verification. The area under the curve of PA and FTA was>0.7, and the hub genes participated in the Relaxin Signaling Pathway, focal adhesion, and other pathways. The construction of the mRNA-miRNA interaction network yielded 11 important miRNAs, while gene-targeting drug prediction identified four targeted drugs with possible effects. This bioinformatics study demonstrated that cell proliferation and tumor suppression and the hub genes co-occurring in PA and FTA, have important effects on the occurrence and progression of two diseases, which make them potential diagnostic biomarkers and therapeutic targets.

Identification of monocyte-associated biomarkers in systemic lupus erythematosus and their pan-cancer analysis.

Immune dysregulation is not only a pathogenic mechanism in systemic lupus erythematosus (SLE) but also a potential cause of the link between SLE and cancer. The current understanding of SLE monocyte-associated biomarkers is limited, and the precise mechanism behind the link between SLE and cancer is uncertain. By using WGCNA and immune infiltration to analyze the GSE72326 dataset, we determined the most pertinent modules for monocytes and discovered eight candidate hub genes from them. The limma software was used to find genes that were differently expressed in SLE. The genes that overlapped between the two were chosen using a Venn diagram as the essential genes related to monocytes in SLE, and the essential genes were verified by several datasets. Correlation analysis and GSEA analysis were used to examine the probable immunological pathways connected to key genes. We examined the expression of hub genes in cancer and their interaction with monocytes using the GEPIA and TIMER databases to understand the significance of essential genes in tumorigenesis. In addition, we performed transcription factor identification. We discovered three biomarkers (IFI30, BLVRA, and RIN2) that are mostly involved in interferon-related signaling pathways and are associated with monocyte-mediated immune responses in SLE. The three important genes are also strongly expressed in a number of malignancies and have a relationship with monocytes. As a result, IFI30, BLVRA, and RIN2 may act as SLE-associated biomarkers of monocytes and as a bridge between SLE and tumors. We proposed that interferon-related signaling pathways might function as possible mediators of cancer risk in SLE.

All-trans retinoic acid inhibits oxidative stress via ACE2/Ang (1-7)/MasR pathway in renal tubular epithelial cells stimulated with high glucose.

The aim of this study was to investigate the effects of all-trans retinoic acid (atRA) on oxidative stress in renal tubular epithelial cells induced by high glucose (HG) and its potential mechanism. We investigated the effects of atRA in HG-induced renal epithelial cell line HK-2. Seven groups were designed for this experiment: negative control, mannitol, high-glucose (HG), HG combined with a low concentration of atRA, HG combined with a middle concentration of atRA, HG combined with a high concentration of atRA, and HG combined with captopril. After 48 h of incubation, oxidative stress factor expression in the supernatant was detected by enzyme-linked immunosorbent assay. Reactive oxygen species and cell apoptosis expression were assessed by flow cytometry. NADPH oxidase, fibrosis factor, and angiotensin-converting enzyme 2/angiotensin (1-7)/mas receptor (ACE2/Ang (1-7)/MasR) pathway-related protein expressions were determined by western blot analysis. The expressions of oxidative stress factors, NADPH oxidase components, and fibrosis factors were significantly higher after HG treatment. Apoptosis of HK2 cells in the HG group was also significantly higher. AtRA could reverse the above abnormal changes in a concentration-dependent manner. HG significantly promoted the expression of ACE, Ang II, and Ang II type 1 receptor (AT1R), whereas it inhibited the expression of ACE2, Ang (1-7), and MasR. With the elevation of concentration, atRA could gradually suppress the expression of ACE, Ang II, and AT1R, but facilitate ACE2, Ang (1-7), and MasR. These results were statistically significant. AtRA could significantly inhibit oxidative stress and apoptosis of renal tubular epithelial cells induced by HG. The mechanism may inhibit the ACE/Ang II/AT1R pathway and/or activate ACE2/Ang (1-7)/MasR pathway.

Risk Factors of Acute Kidney Injury in ECMO Patients: A Systematic Review and Meta-Analysis.

PURPOSE: Acute kidney injury (AKI) is one of the most common complications in patients receiving extracorporeal membrane oxygenation (ECMO), but there is no systematic analysis regarding its risk factors. This meta-analysis aims to determine the risk factors of AKI in adult patients with ECMO treatment. METHODS: Two authors independently carried out a systemic literature search using PubMed, Web of Science, and Embase until April 20, 2020 (inclusive) to enroll 12 studies reporting the necessary clinical characteristics. The Gender (male), age, APACHE II score, SOFA score, cancer, diabetes mellitus (DM), intra-aortic balloon pump (IABP), postcardiotomy, and ECMO supporting duration were pooled for further analysis by STATA. RESULTS: Adult patients receiving ECMO who develop AKI and severe AKI incidents are usually older or have a higher APACHE II scores; in addition, severe AKI is related to higher SOFA scores, DM, and longer duration of ECMO support. CONCLUSIONS: Patients with these clinical characteristics should be paid more attention during ECMO. There remains a need for additional studies to validate these conclusions and to detect additional AKI risk factors for ECMO patients.

Acute Kidney Injury During Extracorporeal Membrane Oxygenation: VA ECMO Versus VV ECMO.

PURPOSE: Acute kidney injury (AKI) has been reported to be one of the most common complications in patients receiving extracorporeal membrane oxygenation (ECMO), yet variations in AKI between different types of ECMO remain unclear. This meta-analysis systematically compares AKI/severe AKI in adult patients requiring different types of ECMO. METHODS: Two authors independently performed a literature search using PubMed, Web of Science, and Embase, encompassing publications up until April 20, 2020 (inclusive). The number of AKI patients, including patients who required/did not require renal replacement therapy (RRT), and deceased patients with AKI/severe AKI, who received different types of ECMO were collated and analyzed using STATA. RESULTS: The results indicated that there were no significant differences in the risk of AKI/severe AKI among different types of ECMO. However, the presence of AKI and severe AKI during veno-arterial (VA) ECMO was more strongly associated with mortality. CONCLUSIONS: Although mortality rates related to AKI/severe AKI during VV ECMO are high, the occurrence of AKI/severe AKI during VA ECMO should be given greater attention, as these instances are considered strong indicators of patient deterioration and even death. Additional studies are needed to corroborate these findings.

Polymeric RNAi Constructs Tailored with Appreciable Transcellular Trafficking Functions for Potential Suppression of Parathyroid Hormone Production.

Polymeric small interfering RNA (siRNA) conjugate was elaborated to sequentially circumvent the predefined biological barriers encountered in the journey of transcellular delivery of siRNA into cytosol. Herein, classic ring-opening polymerization was employed for synthesis of well-defined poly(amino acid) derivatives possessing an array of carboxyl groups in an attempt to resemble the structural characteristics of hyaluronan. Furthermore, the hyaluronan-like synthetic was conjugated with a multiple of siRNA through a glutathione (GSH)-responsive disulfide linkage. The siRNA conjugate appeared to utilize the hyaluronan-specific receptors of CD44 for cell internalization, indicating similar functionalities to our hyaluronan-mimicking synthetic. Furthermore, the carboxyl groups of hyaluronan-like synthetics were designed to be selectively detached in subcellular acidic endosomes/lysosomes and transform into the cytomembrane-disruptive flanking ethylenediamine moieties, which appeared to be crucial in facilitating translocation of siRNA payloads from entrapment and degradation in lysosomes toward the cytosol. Eventually, active siRNA could be smoothly released from the synthetic due to the GSH cleavage disulfide linkage (disulfide), consequently accounting for potent RNA knockdown activities (>90%) toward cancerous cells. In addition, appreciable knockdown of parathyroid hormone was also achieved from our proposed siRNA conjugates in parathyroid cells. Hence, the elaborated siRNA conjugate showed tremendous potential in treatment of hyperparathyroidism, and could be developed further for systemic RNA interference (RNAi) therapeutics. Moreover, this study could also be the first example of a synthetic mimic to hyaluronan acquiring its functionalities, which could have important implications for further development of biomimic materials in pursuit of biomedical applications.

Acute Kidney Injury in Adult Patients With Hepatocellular Carcinoma After TACE or Hepatectomy Treatment.

Background: Acute kidney injury (AKI) is one of the most common complications in patients with cancer, yet the specific reasons, mechanisms, and the influence of AKI are not clear in hepatocellular carcinoma (HCC) after treatment. This meta-analysis aimed to find out the risk factors and the impact on mortality of AKI in adult patients with HCC after treatment using available published data. Methods: We performed a systemic literature search using PubMed, Web of Science, and Embase, encompassing publications up until November 30, 2021 (inclusive), with 17 cohort studies involving 11,865 patients that fulfilled the prespecified criteria for inclusion in the meta-analysis. The number of AKI/non-AKI patients identified by risk factors, the number of AKI/non-AKI-related deaths, the incidence rates, the mortality rates, and the irreversible rates of AKI were derived and analyzed using STATA. Results: Age, diabetes mellitus (DM), and the number of transarterial chemoembolization (TACE) sessions are risk factors for AKI in patients with HCC after TACE. On the other hand, male gender, age, DM, major resection of the liver, and operation-related transfusion are risk factors for AKI in patients with HCC after hepatectomy. The risk of mortality in those with renal failure due to AKI was up to 4.74 times higher than in those without AKI in a short-term observation period after TACE treatment. Conclusions: Attention should be paid to the risk of AKI in HCC patients with DM. The occurrence of AKI during TACE treatment is especially dangerous and should be considered a strong red flag, obviously with regard to the extremely high risk of death in a short period. Furthermore, studies are needed to detect more associations of AKI in patients with HCC.