Immunomodulatory role for MicroRNAs: Regulation of PD-1/PD-L1 and CTLA-4 immune checkpoints expression.
- 作者列表："Skafi N","Fayyad-Kazan M","Badran B
:The development and progression of different pathologies including, cancer, are associated with suppressed immune responses. This restrained immune activity could be associated with the activation of different immune checkpoint pathways that mediate immunosuppressive functions. Therapeutic Protocols based on abolishing the activity of immune check points provided a promising potential for treating cancer. Among the distinct known immune checkpoints, PD-1/PD-L1 and CTLA-4, are the most studied and have been the focus for development of different blocking agents. Monoclonal antibodies that can block PD-1, PD-L1 or CTLA4 have been approved for treatment of different cancers. MicroRNAs (miRNAs), short non-coding regulatory RNA molecules, could repress mRNA expression at a post-transcriptional level. Many miRNAs have been reported to modulate the expression of CTLA-4 and PD-1/PD-L1, either directly or indirectly, in multiple pathological cases, mainly cancer. In this review, after a brief introduction about T cell activation and immune checkpoints, the miRNAs regulating the expression of CTLA-4 and PD-1/PD-L1 are discussed with highlights on their role in cancer. Many of these miRNAs could serve as novel treatments in different types of cancer as detailed throughout the review.
: 包括癌症在内的不同病理的发展和进展与抑制的免疫应答有关。这种受抑制的免疫活性可能与介导免疫抑制功能的不同免疫检查点途径的激活有关。基于消除免疫检查点活性的治疗方案提供了治疗癌症的有希望的潜力。在不同的已知免疫检查点中，PD-1/PD-L1和CTLA-4是研究最多的，并且是开发不同阻断剂的焦点。可阻断PD-1、PD-L1或CTLA4的单克隆抗体已被批准用于治疗不同的癌症。微小RNA (mirna)，短非编码调节RNA分子，可以在转录后水平抑制mRNA表达。已经报道了许多mirna在多种病理情况 (主要是癌症) 中直接或间接调节CTLA-4和PD-1/PD-L1的表达。在这篇综述中，在简要介绍了T细胞活化和免疫检查点之后，讨论了调控CTLA-4和PD-1/PD-L1表达的mirna，并重点介绍了它们在癌症中的作用。这些mirna中的许多可以作为不同类型癌症的新治疗，如在整个综述中详细描述的。
METHODS::More than 10 years after the Centers for Disease Control and Prevention recommended routine HIV testing for patients in emergency departments (ED) and other clinical settings, as many as three out of four patients may not be offered testing, and those who are offered testing frequently decline. The current study examines how participant characteristics, including demographics and reported substance use, influence the efficacy of a video-based intervention designed to increase HIV testing among ED patients who initially declined tests offered by hospital staff. Data from three separate trials in a high volume New York City ED were merged to determine whether patients (N = 560) were more likely to test post-intervention if: (1) they resembled people who appeared onscreen in terms of gender or race; or (2) they reported problem substance use. Chi Square and logistic regression analyses indicated demographic concordance did not significantly increase likelihood of accepting an HIV test. However, participants who reported problem substance use (n = 231) were significantly more likely to test for HIV in comparison to participants who reported either no problem substance use (n = 190) or no substance use at all (n = 125) (x2 = 6.830, p < 0.05). Specifically, 36.4% of patients who reported problem substance use tested for HIV post-intervention compared to 30.5% of patients who did not report problem substance use and 28.8% of participants who did not report substance use at all. This may be an important finding because substance use, including heavy alcohol or cannabis use, can lead to behaviors that increase HIV risk, such as sex with multiple partners or decreased condom use.
METHODS::HIV self-testing has the potential to improve test access and uptake, but concerns remain regarding counselling and support during and after HIV self-testing. We investigated an oral HIV self-testing strategy together with a mobile phone/tablet application to see if and how it provided counselling and support, and how it might impact test access. This ethnographic study was nested within an ongoing observational cohort study in Cape Town, South Africa. Qualitative data was collected from study participants and study staff using 33 semi-structured interviews, one focus group discussion, and observation notes. The app provided information and guidance while also addressing privacy concerns. The flexibility and support provided by the strategy gave participants more control in choosing whom they included during testing. Accessibility concerns included smartphone access and usability issues for older and rural users. The adaptable access and support of this strategy could aid in expanding test access in South Africa.
METHODS:BACKGROUND:Several Kell-system antibodies are known to cause direct agglutination. Also, some specificities, such as anti-Ku, have been reported to react only via the indirect antiglobulin test (IAT). METHODS:Herein, we describe the case of a 61-year-old alloimmunized white woman who presented to an outside hospital with a gastrointestinal (GI) bleed and a "possible anti-Ku" was reported with 3+ reactivity at PEG-IAT and at Ficin-IAT; in addition to an unidentified cold antibody. Subsequently, when the patient presented to a second outside hospital, an anti-Ku that caused 3+ to 4+ reactions at saline-immediate spin (IS) was identified. The reactivity was evaluated with 0.01-M dithiothreitol (DTT) treatment of the plasma. RESULTS:It was determined that the strong agglutination with saline-IS was caused by immunoglobulin (Ig)M anti-Ku. CONCLUSION:To our knowledge, this is the first reported case of an IgM anti-Ku.