Bottom-up analysis of emergent properties of N-acetylcysteine as an adjuvant therapy for COVID-19

N-acetylcysteine (NAC) is an abundantly available antioxidant with a wide range of antidotal properties currently best studied for its use in treating acetaminophen overdose. It has a robustly established safety profile with easily tolerated side effects and presents the Food and Drug Administration's approval for use in treating acetaminophen overdose patients. It has been proven efficacious in off-label uses, such as in respiratory diseases, heart disease, cancer, human immunodeficiency virus infection, and seasonal influenza. Clinical trials have recently shown that NAC's capacity to replenish glutathione stores may significantly improve coronavirus disease 2019 (COVID-19) outcomes, especially in high risk individuals. Interestingly, individuals with glucose 6-phosphate dehydrogenase deficiency have been shown to experience even greater benefit. The same study has concluded that NAC's ability to mitigate the impact of the cytokine storm and prevent elevation of liver enzymes, C-reactive protein, and ferritin is associated with higher success rates weaning from the ventilator and return to normal function in COVID-19 patients. Considering the background knowledge of biochemistry, current uses of NAC in clinical practice, and newly acquired evidence on its potential efficacy against COVID-19, it is worthwhile to investigate further whether this agent can be used as a treatment or adjuvant for COVID-19.     

HIV-1包膜蛋白2G12和2F5中和表位的改造对假病毒形成及中和活性的影响

目的 研究HIV-1膜蛋白(Env)特定中和表位的改造对功能性假病毒形成及中和活性的影响.方法 采用环形诱变及Dpn I筛选的方法对Env进行定点突变,将2G12和2F5两个中和表位整合入不含该表位的BC亚型的Env上,比较改造对假病毒的形成情况及对2G12和2F5单抗的中和活性的影响.结果 对5株假病毒(BC02、BE03、BC04、BC05和BC12)的Env特定中和表位进行改造,其中BC04和BCl2的2G12表位改造后,不能形成假病毒,BC02、BC03和BC05增加2G12和2F5两个表位后,仍能够形成假病毒,且假病毒滴度较改造前无明显变化,改造后的BC03假病毒较改造前对单抗2G12和2175的中和活性均有所提高,而改造后的BE02和BC05假病毒较改造前对单抗2F5的中和活性增强,而对单抗2G12的中和活性无变化.结论 2G12中和表位部分位点的改造影响假病毒的形成,中和表位的增加能够提高单抗2G12的中和活性,为免疫原的优化提供了新思路.     

Dangerous liaisons: complement,coagulation, and kallikrein/kinin cross-talk act as a linchpin in the events leading to thromboinflammation

Innate immunity is fundamental to our defense against microorganisms. Physiologically, the intravascular innate immune system acts as a purging system that identifies and removes foreign substances leading to thromboinflammatory responses, tissue remodeling, and repair. It is also a key contributor to the adverse effects observed in many diseases and therapies involving biomaterials and therapeutic cells/organs. The intravascular innate immune system consists of the cascade systems of the blood (the complement, contact, coagulation, and fibrinolytic systems), the blood cells (polymorphonuclear cells, monocytes, platelets), and the endothelial cell lining of the vessels. Activation of the intravascular innate immune system in vivo leads to thromboinflammation that can be activated by several of the system's pathways and that initiates repair after tissue damage and leads to adverse reactions in several disorders and treatment modalities. In this review, we summarize the current knowledge in the field and discuss the obstacles that exist in order to study the cross-talk between the components of the intravascular innate immune system. These include the use of purified in vitro systems, animal models and various types of anticoagulants. In order to avoid some of these obstacles we have developed specialized human whole blood models that allow investigation of the cross-talk between the various cascade systems and the blood cells. We in particular stress that platelets are involved in these interactions and that the lectin pathway of the complement system is an emerging part of innate immunity that interacts with the contact/coagulation system. Understanding the resulting thromboinflammation will allow development of new therapeutic modalities.     

Association between CD226 polymorphism and soluble levels in rheumatoid arthritis: Relationship with clinical activity

Objective: To study the relation between CD226 rs763361 gene polymorphism and CD226 serum level and to evaluate their role in susceptibility and disease activity of RA in a cohort of Egyptian individuals.

Methods: The serum level of CD226 was measured using a suitable ELISA kit and the CD226 rs763361 gene polymorphism was typed by PCR-RFLP for 112 RA patients and 100 healthy controls.

Results: Significant association with RA was found with CD226 T allele (OR (95%CI) = 1.6 (1.04–2.4), P = 0.032), and higher CD226 serum level (P = 0.001). Higher CD226 levels were associated with higher ESR values (P = 0.035), positive CRP (0.048), increased number of tender joints (P = 0.045), and higher DAS score (P = 0.035). Serum CD226 is an independent risk factor for the prediction of RA (P = 0.001). No correlations were found between the serum level of CD226 and different CD226 genotypes and also between them and RA activity grades.

Conclusion: The CD226 T allele may be susceptibility risk factors for the development of RA and the higher serum level of CD226 may be involved in the pathogenesis of RA in Egyptian patients. The serum level of CD226 and not CD226 genotypes could be considered as an independent risk factor for the prediction of RA within healthy individuals and also for RA disease activity.     

Morphological analysis of degeneration and regeneration of syncytiotrophoblast in first trimester placental villi during organ culture

We have recently shown using dansyl-L-lysine exclusion studies that the release of human chorionic gonadotrophin (HCG) in conjunction with L- lactate dehydrogenase (LDH) from first trimester villi during organ culture is symptomatic of syncytiotrophoblast degeneration. The purpose of this study was to examine chorionic villi at the ultrastructural level in order to determine events occurring during organ culture. The tissue was sampled after 0, 24, 48 and 120 h in culture and processed for electron microscopy. In addition to confirming the previously recorded syncytial degeneration, the electron micrographs showed clearly the generation of a new syncytiotrophoblast layer. The new layer, derived from differentiating cytotrophoblast cells, was largely formed by 48 h and was maintained for at least 120 h in culture. This study demonstrates a model which provides an opportunity to study the differentiation of cytotrophoblast cells whilst they retain their anatomical relationships within the villous structure.      

勃脉力A注射液对体外循环心脏手术患者肝功能的影响

目的 探讨勃脉力A注射液对体外循环心脏手术患者肝功能的影响.方法 选择术前肝功能正常、无肝炎病史的行体外循环心脏手术患者60名,随机分为勃脉力A组(P组)和林格液组(R组).所有患者均在术前、术后2h、1d、3d、7d分别采肘正中静脉血和挠动脉血:静脉血分离血清后应用自动血生化分析仪检测血清中天冬氨酸转氨酶和丙氨酸氨基转移酶,以了解患者的肝脏功能改变;抽取动脉血查乳酸浓度.术中及术后密切观察患者血压、心率、中心静脉压、尿量等,观察并记录患者拔管及停留ICU时间.结果 与R组相比较,在术后各时间点P组ALT、AST及乳酸浓度均显著降低(P﹤0.05),并且拔除气管导管时间和停留ICU时间均有所缩短.结论 勃脉力A注射液能够显著降低体外循环术中乳酸浓度,并能改善患者肝功能,非常适用于体外循环手术.     

Comparing Two Approaches to Acquiring HIV-Risk Data from Puerto Rican Women with Severe Mental Illness

Renewed interest has been expressed by researchers in mixed-method assessment that employs both quantitative and qualitative techniques in an expansive style that utilizes a variety of tactics to address research questions. Participants consisted of Puerto Rican women with severe mental illness living in Cuyahoga County, Ohio. The women were shadowed over a 2-year period to observe and verify behaviors that were self-reported using standardized instruments in semi-structured interviews. Concurrent criterion-related validity was employed to determine the extent of the correlation between responses obtained from the two approaches. Forty-four percent of the women were diagnosed with major depression and the mean overall GAF score was 58.5 ± 14.5. A comparison of the data collected using the different methodologies revealed that inconsistent and contradictory responses are not uncommon. The mixed-method design provided a more complete way of obtaining HIV-risk behavior data. Researchers and clinicians could benefit from mixed methods research that can provide greater opportunities to obtain data of a sensitive nature.