COVID-19 is associated with neuropsychiatric complications, the most frequent one being anxiety. Multiple biological and psychosocial factors contribute to anxiety in COVID-19. Among the biological factors, stress, genetics, gender, immune system, resilience, anosmia, hypogeusia, and central nervous system infection with SARS-CoV-2 are key. Anxiety is a complication of COVID-19 that may exacerbate the infection course, and the infection may exacerbate anxiety. We present the mechanisms of anxiety in symptomatic or asymptomatic COVID-19. We discuss the presentation of anxiety in patients without or with prior psychiatric illness, and with co-morbidities. Timely diagnosis and management of anxiety in COVID-19 patients is important. Given the frequent complication of COVID-19 with Acute Respiratory Distress Syndrome and Intensive Care Unit stay, anxiety may be a long-term complication. We review the diagnostic tools for anxiety in COVID-19, and summarise pharmacologic and non-pharmacologic treatments. We provide recommendations for diagnosis, treatment, prevention and follow up of anxiety in COVID-19.Key pointsPatients with COVID-19 (symptomatic or asymptomatic) exhibit a high frequency of neuropsychiatric complications with highest percentage attributed to anxiety.Multiple biological and psychosocial risk factors for anxiety exist in COVID-19-ill individuals. Biological risk factors include stress, resilience, genetics, gender, age, immune system, direct infection of the central nervous system (CNS) with SARS-CoV-2, comorbid psychiatric and general medical illnesses, ARDS and ICU stay. Anosmia and hypogeusia are COVID-19-specific anxiety risk factors. Knowledge of the anxiety risk factors is essential to focus on timely interventions, because anxiety may be a complication of and exacerbate the COVID-19 course.An inverse correlation exists between resilience and anxiety because of COVID-19, and therefore efforts should be made to increase resilience in COVID-19 patients.In COVID-19, important anxiety mechanism is neuroinflammation resulting from activation of the immune system and an ensuing cytokine storm.The general approach to management of anxiety in COVID-19 should be compassionate, similar to that during trauma or disaster, with efforts focussed on instilling a sense of hope and resilience.In selecting pharmacological treatment of anxiety, the stress response and immune system effects should be key. Medications with cardio-respiratory adverse effects should be avoided in patients with respiratory problems.Anxiety is a disorder that will require for long-term follow up at least one month after COVID-19.

Presentation and management of anxiety in individuals with acute symptomatic or asymptomatic COVID-19 infection, and in the post-COVID-19 recovery phase.

Objective Bladder cancer (BC) is the most common malignancy in the urinary system and is prone to recurrence and metastasis. Pyroptosis is a kind of cell necrosis that is triggered by the gasdermin protein family. lncRNAs are noncoding RNAs that are more than 200 nucleotides long. Both pyroptosis and lncRNAs are associated with tumor development and progression. This study is aimed at exploring and establishing a prognostic signature of BC based on pyroptosis-related lncRNAs. Methods In this study, The Cancer Genome Atlas (TCGA) database provided us with the RNA sequencing transcriptome data of bladder cancer patients, and we identified differentially expressed pyroptosis-related lncRNAs in bladder cancer. Then, the prognostic significance of these lncRNAs was assessed using univariate Cox regression analysis and LASSO regression analysis. Subsequently, 4 pyroptosis-related lncRNAs, namely, AL121652.1, AL161729.4, AC007128.1, and AC124312.3, were identified by multivariate Cox regression analysis, thus constructing the prognostic risk model. Then, we compared the levels of immune infiltration, differences in cell function, immune checkpoints, and m6A-related gene expression levels between the high- and low-risk groups. Result Patients were divided into low-risk or high-risk groups based on the median risk score. Kaplan–Meier survival analysis indicated that the overall survival of bladder cancer patients in the low-risk group was substantially superior to that in the high-risk group (p < 0.001). The receiver operating characteristic (ROC) curve further confirmed the credibility of our model. Moreover, gene set enrichment analysis (GSEA) indicated that these were different signal pathways significantly enriched between the two groups. Immune infiltration, immune checkpoint, and N6-methyladenosine-related gene analysis also reflected that there were notable differences between the two groups. Conclusion Therefore, this prognostic risk model is based on the level of pyroptotic lncRNAs, which is conducive to individualized assessment of the risk of patients and provides a reference for clinical treatment. This will also help provide insights into the prognosis and treatment of bladder cancer.

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Prognosis Risk Model Based on Pyroptosis-Related lncRNAs for Bladder Cancer

Introduction Cuproptosis is a novel identified regulated cell death (RCD), which is correlated with the development, treatment response and prognosis of cancer. However, the potential role of cuproptosis-related genes (CRGs) in the tumor microenvironment (TME) of gastric cancer (GC) remains unknown. Methods Transcriptome profiling, somatic mutation, somatic copy number alteration and clinical data of GC samples were downloaded from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) database to describe the alterations of CRGs from genetic and transcriptional fields. Differential, survival and univariate cox regression analyses of CRGs were carried out to investigate the role of CRGs in GC. Cuproptosis molecular subtypes were identified by using consensus unsupervised clustering analysis based on the expression profiles of CRGs, and further analyzed by GO and KEGG gene set variation analyses (GSVA). Genes in distinct molecular subtypes were also analyzed by GO and KEGG gene enrichment analyses (GSEA). Differentially expressed genes (DEGs) were screened out from distinct molecular subtypes and further analyzed by GO enrichment analysis and univariate cox regression analysis. Consensus clustering analysis of prognostic DEGs was performed to identify genomic subtypes. Next, patients were randomly categorized into the training and testing group at a ratio of 1:1. CRG Risk scoring system was constructed through logistic least absolute shrinkage and selection operator (LASSO) cox regression analysis, univariate and multivariate cox analyses in the training group and validated in the testing and combined groups. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to evaluate the expression of key Risk scoring genes. Sensitivity and specificity of Risk scoring system were examined by using receiver operating characteristic (ROC) curves. pRRophetic package in R was used to investigate the therapeutic effects of drugs in high- and low- risk score group. Finally, the nomogram scoring system was developed to predict patients’ survival through incorporating the clinicopathological features and CRG Risk score. Results Most CRGs were up-regulated in tumor tissues and showed a relatively high mutation frequency. Survival and univariate cox regression analysis revealed that LIAS and FDX1 were significantly associated with GC patients’ survival. After consensus unsupervised clustering analysis, GC patients were classified into two cuproptosis molecular subtypes, which were significantly associated with clinical features (gender, age, grade and TNM stage), prognosis, metabolic related pathways and immune cell infiltration in TME of GC. GO enrichment analyses of 84 DEGs, obtained from distinct molecular subtypes, revealed that DEGs primarily enriched in the regulation of metabolism and intracellular/extracellular structure in GC. Univariate cox regression analysis of 84 DEGs further screened out 32 prognostic DEGs. According to the expression profiles of 32 prognostic DEGs, patients were re-classified into two gene subtypes, which were significantly associated with patients’ age, grade, T and N stage, and survival of patients. Nest, the Risk score system was constructed with moderate sensitivity and specificity. A high CRG Risk score, characterized by decreased microsatellite instability-high (MSI-H), tumor mutation burden (TMB) and cancer stem cell (CSC) index, and high stromal and immune score in TME, indicated poor survival. Four of five key Risk scoring genes expression were dysregulated in tumor compared with normal samples. Moreover, CRG Risk score was greatly related with sensitivity of multiple drugs. Finally, we established a highly accurate nomogram for promoting the clinical applicability of the CRG Risk scoring system. Discussion Our comprehensive analysis of CRGs in GC demonstrated their potential roles in TME, clinicopathological features, and prognosis. These findings may improve our understanding of CRGs in GC and provide new perceptions for doctors to predict prognosis and develop more effective and personalized therapy strategies.

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Identification of cuproptosis-related subtypes, construction of a prognosis model, and tumor microenvironment landscape in gastric cancer

Simple Summary It is urgent to identify new biomarkers for diagnosis, prognostication, and therapeutic targets of acute myeloid leukemia (AML) so as to develop more effective surveillance and treatment programs. Ferroptosis is a crucial, iron-dependent regulated cell death driven by excessive accumulation of lipid hydroperoxides. Accumulating evidence has proven that dysregulated ferroptosis is implicated in tumor progression and is becoming an emerging therapeutic target for the treatment of AML. However, the effect of circRNAs on ferroptosis and the development of AML remain unclear. In this study, we provide the first line of evidence that circZBTB46 is an important oncogenic circRNA as well as a diagnostic or prognostic biomarker for AML. CircZBTB46 exerts a critical role in promoting the expression of SCD to protect AML cells from ferroptotic cell death. Importantly, our findings may offer a potential therapeutic target, circZBTB46, to broaden treatment options for human AML, especially concerning the use of combined treatment with ferroptosis inducers. Abstract Circular RNAs (circRNAs) have been shown to be closely linked to the tumorigenesis and treatment response of hematological malignancies. However, the biological functions and clinical implications of circRNAs in acute myeloid leukemia (AML) remain largely unknown. CircRNA microarray datasets were analyzed to screen differentially expressed circRNAs in AML patients. It was found that circZBTB46 was significantly upregulated in AML patients and AML cells. Moreover, the expression of circZBTB46 was associated with the stages of AML patients and showed high sensitivity and specificity for diagnosing AML. Silencing of circZBTB46 inhibited AML cell proliferation and induced cell cycle arrest. Importantly, the depletion of circZBTB46 notably increased ferroptosis and enhanced RSL3-induced ferroptosis in AML cells. Mechanistically, circZBTB46 upregulated the expression of stearoyl-CoA desaturase 1 (SCD) possibly by acting as a miRNA sponge. Finally, the circZBTB46 knockdown repressed the tumor growth of AML in vivo. In conclusion, circZBTB46 protects AML cells from ferroptosis and promotes the proliferation by upregulating SCD, thus suggesting that circZBTB46 may be a potential therapeutic target for AML.

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CircZBTB46 Protects Acute Myeloid Leukemia Cells from Ferroptotic Cell Death by Upregulating SCD

Target identification is essential for developing novel therapeutic strategies in diseases. Thioredoxin-interacting protein (TXNIP), also known as thioredoxin-binding protein-2, is a member of the α-arrestin protein family and is regulated by several cellular stress factors. TXNIP overexpression coupled with thioredoxin inhibits its antioxidant functions, thereby increasing oxidative stress. TXNIP is directly involved in inflammatory activation by interacting with Nod-like receptor protein 3 inflammasome. Bone metabolic disorders are associated with aging, oxidative stress, and inflammation. They are characterized by an imbalance between bone formation involving osteoblasts and bone resorption by osteoclasts, and by chondrocyte destruction. The role of TXNIP in bone metabolic diseases has been extensively investigated. Here, we discuss the roles of TXNIP in the regulatory mechanisms of transcription and protein levels and summarize its involvement in bone metabolic disorders such as osteoporosis, osteoarthritis, and rheumatoid arthritis. TXNIP is expressed in osteoblasts, osteoclasts, and chondrocytes and affects the differentiation and functioning of skeletal cells through both redox-dependent and -independent regulatory mechanisms. Therefore, TXNIP is a potential regulatory and functional factor in bone metabolism and a possible new target for the treatment of bone metabolism-related diseases.

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Thioredoxin-interacting protein: A new therapeutic target in bone metabolism disorders?

Background Every year, nearly 170,000 people die from bladder cancer worldwide. A major problem after transurethral resection of bladder tumor is that 40%–80% of the tumors recur. Ferroptosis is a type of regulatory necrosis mediated by iron-catalyzed, excessive oxidation of polyunsaturated fatty acids. Increasing the sensitivity of tumor cells to ferroptosis is a potential treatment option for cancer. Establishing a diagnostic and prognostic model based on ferroptosis-related genes may provide guidance for the precise treatment of bladder cancer. Methods We downloaded mRNA data in Bladder Cancer from The Cancer Genome Atlas (TCGA) and analyzed differentially expressed genes (DEGs) based on and extract ferroptosis-related genes. We identified relevant pathways and annotate the functions of ferroptosis-related DEGs using Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis (KEGG) and Gene Ontology functions (GO). On the website of Search Tool for Retrieving Interacting Genes database (STRING), we downloaded the protein-protein interactions of DEGs, which were drawn by the Cytoscape software. Then the Cox regression analysis were performed so that the prognostic value of ferroptosis-related genes and survival time are combined to identify survival- and ferroptosis-related genes and establish a prognostic formula. Survival analysis and receiver operating characteristic curve (ROC) validation were then performed. Finally, risk curves and nomograms were generated for both groups to predict survival. Results Eight ferroptosis-related genes with prognostic value (ISCU, NFE2L2, MAFG, ZEB1, VDAC2, TXNIP, SCD, JDP2) were identified. With clinical data, we established a prognostic model to provide promising diagnostic and prognostic information of bladder cancer based on the eight ferroptosis-related genes. Conclusion This study found that the ferroptosis-related genes is associated with bladder cancer, which may serve as new target for the treatment of bladder cancer.

Biological Functions and Prognostic Value of Ferroptosis-Related Genes in Bladder Cancer

SARS-CoV-2 is one of the beta-coronaviruses with the spike protein. It invades host cells by binding to angiotensin converting enzyme 2 (ACE2). This newly discovered virus can result in excessive inflammation and immune pathological damage, as shown by a decreased number of peripheral lymphocytes, increased levels of cytokines, and damages of lung, heart, liver, kidney, and other organs. Effective therapeutic modalities such as new antiviral drugs and vaccines against this emerging virus need to be thoroughly studied and developed. However, so far the only recognized but mild progress in this area is the screening of old drugs for new uses. Therefore, rapid and accurate laboratory SARS-CoV-2 testing approaches are the important basis of identification and blockage of COVID-19 transmission. For COVID-19 patients with different clinical classifications (mild, common, severe, and critically severe), dynamic monitoring of functional indicators of susceptible and vital organs is an important strategy for evaluating therapeutic efficacy and prognosis. In this review, we summarized SARS-CoV-2 laboratory diagnostic schemes, pathophysiological indices of tissues and organs of COVID-19 patients, and laboratory diagnostic strategies for distinct disease stages. Further, we discussed the importance of hierarchical management and dynamic observation in SARS-CoV-2 laboratory diagnostics. We then summed up the advance in SARS-CoV-2 testing technology and described the prospect of intelligent medicine in the prevention of infectious disease outbreaks.

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Cheng Wang

Papers

Biological Functions and Prognostic Value of Ferroptosis-Related Genes in Bladder Cancer

COVID-19: advance in laboratory diagnostic strategy and technology.