Crosstalk between Platelets and the Immune System: Old Systems with New Discoveries

Platelets are small anucleate cells circulating in the blood. It has been recognized for more than 100 years that platelet adhesion and aggregation at the site of vascular injury are critical events in hemostasis and thrombosis; however, recent studies demonstrated that, in addition to these classic roles, platelets also have important functions in inflammation and the immune response. Platelets contain many proinflammatory molecules and cytokines (e.g., P-selectin, CD40L, IL-1β, etc.), which support leukocyte trafficking, modulate immunoglobulin class switch, and germinal center formation. Platelets express several functional Toll-like receptors (TLRs), such as TLR-2, TLR-4, and TLR-9, which may potentially link innate immunity with thrombosis. Interestingly, platelets also contain multiple anti-inflammatory molecules and cytokines (e.g., transforming growth factor-β and thrombospondin-1). Emerging evidence also suggests that platelets are involved in lymphatic vessel development by directly interacting with lymphatic endothelial cells through C-type lectin-like receptor 2. Besides the active contributions of platelets to the immune system, platelets are passively targeted in several immune-mediated diseases, such as autoimmune thrombocytopenia, infection-associated thrombocytopenia, and fetal and neonatal alloimmune thrombocytopenia. These data suggest that platelets are important immune cells and may contribute to innate and adaptive immunity under both physiological and pathological conditions

A nomogram for prediction of deep venous thrombosis risk in elderly femoral intertrochanteric fracture patients: A dual-center retrospective study

ObjectiveDeep venous thrombosis (DVT) of the lower extremity is a common perioperative complication of femoral intertrochanteric fracture. This study aimed to identify the risk factors of lower extremity deep vein thrombosis (DVT) in elderly femoral intertrochanteric fracture patients and establish a nomogram model.MethodsFrom August 2014 to June 2021, a total of 1,652 femoral intertrochanteric fracture patients over the age of 65 were enrolled in our study. We distinguished independent risk factors by univariate and multivariate Cox analyses. A nomogram model was then built, and the discriminative and calibration of the model was evaluated through receiver operating characteristics (ROC) and calibration plots.ResultsA total of 378 patients developed DVT (292 in the training group, 86 in the validation group) while the remaining patients did not. According to the univariate and multivariate Cox analyses results, age (OR = 1.07, 95% CI: 1.04–1.10), fibrinogen (OR = 2.09, 95% CI: 1.68–2.60), D-dimer (OR = 1.33, 95% CI: 1.27–1.40), time from injury to admission (OR = 1.78, 95% CI: 1.55–2.05), functional status (OR = 4.21, 95% CI: 2.86–6.20), and diabetes (OR = 1.65, 95% CI: 1.10–2.48) were identified as independent risk factors of DVT. The ROC values for DVT of the training and validation group were 0.862 and 0.912, and the P-value of the Hosmer-Lemeshow calibration test was 0.767.ConclusionThis nomogram model can be used to predict the probability of preoperative DVT in elderly patients with femoral intertrochanteric fracture and guide physician in perioperative thrombosis management

Plant Food Delphinidin-3-Glucoside Significantly Inhibits Platelet Activation and Thrombosis: Novel Protective Roles against Cardiovascular Diseases

Delphinidin-3-glucoside (Dp-3-g) is one of the predominant bioactive compounds of anthocyanins in many plant foods. Although several anthocyanin compounds have been reported to be protective against cardiovascular diseases (CVDs), the direct effect of anthocyanins on platelets, the key players in atherothrombosis, has not been studied. The roles of Dp-3-g in platelet function are completely unknown. The present study investigated the effects of Dp-3-g on platelet activation and several thrombosis models in vitro and in vivo. We found that Dp-3-g significantly inhibited human and murine platelet aggregation in both platelet-rich plasma and purified platelets. It also markedly reduced thrombus growth in human and murine blood in perfusion chambers at both low and high shear rates. Using intravital microscopy, we observed that Dp-3-g decreased platelet deposition, destabilized thrombi, and prolonged the time required for vessel occlusion. Dp-3-g also significantly inhibited thrombus growth in a carotid artery thrombosis model. To elucidate the mechanisms, we examined platelet activation markers via flow cytometry and found that Dp-3-g significantly inhibited the expression of P-selectin, CD63, CD40L, which reflect platelet α- and δ-granule release, and cytosol protein secretion, respectively. We further demonstrated that Dp-3-g downregulated the expression of active integrin αIIbβ3 on platelets, and attenuated fibrinogen binding to platelets following agonist treatment, without interfering with the direct interaction between fibrinogen and integrin αIIbβ3. We found that Dp-3-g reduced phosphorylation of adenosine monophosphate-activated protein kinase, which may contribute to the observed inhibitory effects on platelet activation. Thus, Dp-3-g significantly inhibits platelet activation and attenuates thrombus growth at both arterial and venous shear stresses, which likely contributes to its protective roles against thrombosis and CVDs

Risk factors and nomogram predictive model of surgical site infection in closed pilon fractures

Abstract Objectives In this study, we try to investigate the risk factors of postoperative surgical site infection (SSI) in closed pilon fractures and establish a nomogram prediction model. Methods From January 2012 to June 2021, 516 closed pilon fracture patients were included in this study. Of these, 387 patients were randomly assigned to the training group and 129 patients were assigned to the validation group (3:1). By univariate and multivariate Cox analysis, we identified independent risk factors for postoperative SSI after Pilon fracture. We established a nomogram model and used receiver operating characteristic (ROC) and calibration chart to evaluate its discriminant and calibration. Results SSI occurred in 71 patients in the training group and 23 patients in the validation group. Ultimately, age, preoperative blood sugar, operative time, Tscherne classification and fracture classification were identified as independent risk factors for SSI. The AUC values for SSI of the training and validation group were 0.898 and 0.880, and the P value of the Hosmer–Lemeshow test was 0.125. We established a nomogram prediction model based on age, preoperative blood sugar, operative time, Tscherne classification and fracture classification. Conclusion Our nomogram model had good discrimination and calibration power, so it could be used to predict SSI risk in patients with pilon fracture

Social Avoidance and Social Adjustment in Chinese Preschool Migrant Children: The Moderating Role of Household Chaos and Gender

The present study explored the moderating role of household chaos and gender in the relation between social avoidance and social adjustment among Chinese preschool migrant children. Participants were 148 children (82 boys, Mage = 62.63 months, SD = 0.05) from two kindergartens, Shanghai, People’s Republic of China. Multi-source assessments included: (1) mother ratings of children’s social avoidance; (2) mother ratings of families’ household chaos; (3) teacher ratings of children’s prosocial behavior, peer exclusion, interpersonal skills, and internalizing problems. Results showed that social avoidance significantly predicted peer exclusion among Chinese migrant preschoolers. Moreover, household chaos moderated the relationship between social avoidance and social adjustment. Specifically, at higher levels of household chaos, social avoidance was negatively associated with interpersonal skills. In contrast, social avoidance was not associated with interpersonal skills at a lower level of household chaos. In addition, social avoidance was positively associated with peer exclusion among boys but not girls. The current findings inform us of the importance of reducing household chaos to buffer the negative adjustment among socially avoidant young children who migrated from rural to urban China. The findings also highlight the need to pay particular attention to migrant socially avoidant boys’ development in early childhood and the importance of considering the meaning and implication of social avoidance for migrant preschoolers in Chinese culture

miR-155-5p Promotes Oxalate- and Calcium-Induced Kidney Oxidative Stress Injury by Suppressing MGP Expression

Oxalate and calcium are the major risk factors for calcium oxalate (CaOx) stone formation. However, the exact mechanism remains unclear. This study was designed to confirm the potential function of miR-155-5p in the formation of CaOx induced by oxalate and calcium oxalate monohydrate (COM). The HK-2 cells were treated by the different concentrations of oxalate and COM for 48 h. We found that oxalate and COM treatment significantly increased ROS generation, LDH release, cellular MDA levels, and H2O2 concentration in HK-2 cells. The results of qRT-PCR and western blot showed that expression of NOX2 was upregulated, while that of SOD-2 was downregulated following the treatment with oxalate and COM in HK-2 cells. Moreover, the results of miRNA microarray analysis showed that miR-155-5p was significantly upregulated after oxalate and COM treated in HK-2 cells, but miR-155-5p inhibitor treatment significantly decreased ROS generation, LDH release, cellular MDA levels, and H2O2 concentration in HK-2 cells incubated with oxalate and COM. miR-155-5p negatively regulated the expression level of MGP via directly targeting its 3′-UTR, verified by the Dual-Luciferase Reporter System. In vivo, polarized light optical microphotography showed that CaOx crystal significantly increased in the high-dose oxalate and Ca2+ groups compared to the control group. Furthermore, IHC analyses showed strong positive staining intensity for the NOX-2 protein in the high-dose oxalate and Ca2+-treated mouse kidneys, and miR-155-5p overexpression can further enhance its expression. However, the expression of SOD-2 protein was weakly stained. In conclusion, our study indicates that miR-155-5p promotes oxalate- and COM-induced kidney oxidative stress injury by suppressing MGP expression

Crosstalk between Platelets and the Immune System: Old Systems with New Discoveries

Platelets are small anucleate cells circulating in the blood. It has been recognized for more than 100 years that platelet adhesion and aggregation at the site of vascular injury are critical events in hemostasis and thrombosis; however, recent studies demonstrated that, in addition to these classic roles, platelets also have important functions in inflammation and the immune response. Platelets contain many proinflammatory molecules and cytokines (e.g., P-selectin, CD40L, IL-1β, etc.), which support leukocyte trafficking, modulate immunoglobulin class switch, and germinal center formation. Platelets express several functional Toll-like receptors (TLRs), such as TLR-2, TLR-4, and TLR-9, which may potentially link innate immunity with thrombosis. Interestingly, platelets also contain multiple anti-inflammatory molecules and cytokines (e.g., transforming growth factor-β and thrombospondin-1). Emerging evidence also suggests that platelets are involved in lymphatic vessel development by directly interacting with lymphatic endothelial cells through C-type lectin-like receptor 2. Besides the active contributions of platelets to the immune system, platelets are passively targeted in several immune-mediated diseases, such as autoimmune thrombocytopenia, infection-associated thrombocytopenia, and fetal and neonatal alloimmune thrombocytopenia. These data suggest that platelets are important immune cells and may contribute to innate and adaptive immunity under both physiological and pathological conditions.Peer Reviewe

The Antiviral Effect of <i>Isatis</i> Root Polysaccharide against NADC30-like PRRSV by Transcriptome and Proteome Analysis

(1) Background: In recent years, the porcine reproductive and respiratory syndrome virus (PRRSV) has become a virulent pathogen that has caused devastating diseases and economic losses worldwide in the swine industry. IRPS has attracted extensive attention in the field of virology. However, it is not clear that IRPS has an antiviral effect on PRRSV at gene and protein levels. (2) Methods: We used transcriptomic and proteomic analysis to investigate the antiviral effect of IRPS against PRRSV. Additionally, a microbiome was used to explore the effects of IRPS on gut microbes. (3) Results: IRPS significantly extenuated the pulmonary pathological lesions and inflammatory response. We used transcriptomic and proteomic analysis to investigate the antiviral effect of IRPS against PRRSV. In the porcine model, 1669 differentially expressed genes (DEGs) and 370 differentially expressed proteins (DEPs) were identified. Analysis of the DEG/DEP-related pathways indicated immune-system and infectious-disease (viral) pathways, such as the NOD-like receptor (NLR) signaling pathway, toll-like receptor (TLR) signaling pathway, and Influenza A-associated signaling pathways. It is noteworthy that IRPS can inhibit NLR-dependent gene expression, then reduce the inflammatory damage. IRPS could exert beneficial effects on the host by regulating the structure of intestinal flora. (4) Conclusions: The antiviral effect of IRPS on PRRSV can be directly achieved by omics techniques. Specifically, the antiviral mechanism of IPRS can be better elucidated by screening target genes and proteins using transcriptome and proteome sequencing, and then performing enrichment and classification according to DEGs and DEPs