Indoleamine 2,3-dioxygenase 1 is essential for sustaining durable antibody responses

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Sex- or Gender-specific Differences in the Clinical Presentation,Outcome, and Treatment of SARS-CoV-2

This review describes the sex and gender differences in COVID-19 presentation, treatment, and outcomes. We discuss the differences between the sexes in susceptibility to infection, the role of sex chromosomes on the body's immunologic response and the influence of hormones on the body's response to the virus. Additionally, the sex differences in clinical and laboratory presentation, complications of infection and outcomes, as well as differences in response to treatment and prevention are reviewed.     

Can we increase the speed and efficacy of antidepressant treatments? Part II. Glutamatergic and RNA interference strategies

In the second part we focus on two treatment strategies that may overcome the main limitations of current antidepressant drugs. First, we review the experimental and clinical evidence supporting the use of glutamatergic drugs as fast-acting antidepressants. Secondly, we review the involvement of microRNAs (miRNAs) in the pathophysiology of major depressive disorder (MDD) and the use of small RNAs (e.g.., small interfering RNAs or siRNAs) to knockdown genes in monoaminergic and non-monoaminergic neurons and induce antidepressant-like responses in experimental animals.The development of glutamatergic agents is a promising venue for antidepressant drug development, given the antidepressant properties of the non-competitive NMDA receptor antagonist ketamine. Its unique properties appear to result from the activation of AMPA receptors by a metabolite [(2 S,6 S;2 R,6 R)-hydroxynorketamine (HNK)] and mTOR signaling. These effects increase synaptogenesis in prefrontal cortical pyramidal neurons and enhance serotonergic neurotransmission via descending inputs to the raphe nuclei. This view is supported by the cancellation of ketamine's antidepressant-like effects by inhibition of serotonin synthesis.We also review existing evidence supporting the involvement of miRNAs in MDD and the preclinical use of RNA interference (RNAi) strategies to target genes involved in antidepressant response. Many miRNAs have been associated to MDD, some of which e.g., miR-135 targets genes involved in antidepressant actions. Likewise, SSRI-conjugated siRNA evokes faster and/or more effective antidepressant-like responses. Intranasal application of sertraline-conjugated siRNAs directed to 5-HT_1A receptors and SERT evoked much faster changes of pre- and postsynaptic antidepressant markers than those produced by fluoxetine.     

Comparison of Gravity Flow Rates Between ENFit and Legacy Feeding Tubes

Background: Misconnections between enteral supplies and other access devices have led to significant morbidity and mortality. To reduce misconnections, a standard small‐bore connector has been developed (International Organization for Standards 80369‐8; ENFit). The full impact of transition to this connector is not known, however. Method: Working with major manufacturers and Food and Drug Administration, we obtained ENFit and comparative legacy tubes of variable sizes (low‐profile, 14F, 18F, 20F, and 24F balloon gastrostomies). Gravity enteral feeding was simulated with an empty bolus syringe attached to the feeding tube to be tested. The tube was clamped and filled to the 60‐mL mark with liquid (water, Jevity 1 Cal, Isosource HN, Isosource 1.5 Cal, Two Cal HN, and Nourish). The clamp was released, and time for formula to leave the syringe was recorded. Results: There was no difference in flow rate between the aggregate legacy and ENFit tubes for the low‐profile, 18F, and 20F sizes. The ENFit 14F tubes had a lower flow rate vs the legacy tubes, largely due to the low flow rates seen with the 1 ENFit tube. Similarly, 24F ENFit tubes with some formulas yielded lower flow rates as opposed to legacy. Conclusion: Overall, for the low‐profile, 18F, and 20F sizes, the ENFit tubes had similar flow rates when compared with the legacy tubes. For the 14F and 24F sizes, the flow rate of ENFit tubes was significantly lower, which could result in longer EN delivery for patients who are using these tubes to provide gravity feeding.     

长链非编码RNA与微小RNA相互作用对调控疾病的研究进展

非编码RNA(ncRNA)与基因调控密切相关,ncRNA主要包括微小RNA(miRNA)和长链非编码RNA(lncRNA)。lncRNA与miRNA之间存在着相互调控关系,两者间的相互作用参与了众多疾病的发生发展。本文主要综述其在癌症、心血管疾病、免疫系统和神经系统疾病中的作用及其作用机制。     

Non-coding RNAs as therapeutic targets for preventing myocardial ischemia-reperfusion injury

Introduction: New treatments are required to improve clinical outcomes in patients with acute myocardial infarction (AMI), for reduction of myocardial infarct (MI) size and preventing heart failure. Following AMI, acute ischemia/reperfusion injury (IRI) ensues, resulting in cardiomyocyte death and impaired cardiac function. Emerging studies have implicated a fundamental role for non-coding RNAs (microRNAs [miRNA], and more recently long non-coding RNAs [lncRNA]) in the setting of acute myocardial IRI.

Areas covered: In this article, we discuss the roles of miRNAs and lncRNAs as potential biomarkers and therapeutic targets for the detection and treatment of AMI, review their roles as mediators and effectors of cardioprotection, particularly in the settings of interventions such as ischemic pre- and post-conditioning (IPC & IPost) as well as remote ischemic conditioning (RIC), and highlight future strategies for targeting ncRNAs to reduce MI size and prevent heart failure following AMI.

Expert opinion: Investigating the roles of miRNAs and lncRNAs in the setting of AMI has provided new insights into the pathophysiology underlying acute myocardial IRI, and has identified novel biomarkers and therapeutic targets for detecting and treating AMI. Pharmacological and genetic manipulation of these ncRNAs has the therapeutic potential to improve clinical outcomes in AMI patients.     

Nano in nano: Biosynthesized gold and iron nanoclusters cargo neoplastic exosomes for cancer status biomarking

Timely detection is crucial for successful treatment of cancer. The current study describes a new approach that involves utilization of the tumor cell environment for bioimaging with in-situ biosynthesized nanoscale gold and iron probes and subsequent dissemination of Au-Fe nanoclusters from cargo exosomes within the circulatory system. We have isolated the Au-Fe cargo exosomes from the blood of the treated murine models after in situ biosyntheses from their respective pre-ionic solutions (HAuCl₄, FeCl₂), whereas Na₂SeO₃ supplementation added into Au lethal effect. The microarray data of various differentially expressed genes revealed the up-regulated tumor ablation and metal binding genes in SGC-7901 cell lines after treatment with Au-Fe-Se triplet ionic solution. The isolation of Au-Fe nanoclusters cargo exosomes (nano in nano) after secretion from deeply seated tumors may help in early diagnosis and reveal the tumor ablation status during and after the relevant treatment like radio-chemo therapies et al.     

Transcultural,transdiagnostic, and concurrent validity of a revised metacognitions about symptoms control scale

Anxiety and depression add to the burden of chronic fatigue syndrome (CFS), fibromyalgia (FM), and type 1 diabetes mellitus (T1DM). Metacognitions play a role in this distress. The metacognitions about symptoms control scale (MaSCS) measure metacognitive beliefs regarding symptoms but have weaknesses. The current study created a revised MaSCS (MaSCS‐R) in English, German, and Arabic versions using CFS, FM, and T1DM samples and examined the transcultural, transdiagnostic, and concurrent validity of metacognitions about symptom control. This study used data from 563 participants clinically diagnosed with CFS (n = 124; English), FM (n = 348; German), or T1DM (n = 91; Lebanese). CFS and FM data had been used in earlier published studies but were subjected to new analyses. CFS data were used to create the English version of the MaSCS‐R and FM and T1DM data for German and Arabic versions. Metacognitions about worry, anxiety, depression, and symptom severity were measured. The three MaSCS‐R versions, consisting of two factors (each with four items), had adequate psychometric properties, possessing configural and metric invariance. Metacognitive factors were associated with distress and symptom severity in all three samples. Metacognitions about symptom control have transcultural, transdiagnostic, and concurrent validity.