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With the increasing incidence of kidney diseases, there is an urgent need to develop therapeutic strategies to combat post-injury fibrosis. Immune cells, including platelets, play a pivotal role in this repair process, primarily through their released cytokines. However, the specific role of platelets in kidney injury and subsequent repair remains underexplored. Here, the detrimental role of platelets in renal recovery following ischemia/reperfusion injury and its contribution to acute kidney injury  to chronic kidney disease transition is aimed to investigated. In this study, it is shown that depleting platelets accelerates injury resolution and significantly reduces fibrosis. Employing advanced single-cell and spatial transcriptomic techniques, macrophages as the primary mediators modulated by platelet signals is identified. A novel subset of macrophages, termed cycling M2, which exhibit an M2 phenotype combined with enhanced proliferative activity is uncovered. This subset emerges in the injured kidney during the resolution phase and is modulated by platelet-derived thrombospondin 1 (THBS1) signaling, acquiring profibrotic characteristics. Conversely, targeted inhibition of THBS1 markedly downregulates the cycling M2 macrophage, thereby mitigating fibrotic progression. Overall, this findings highlight the adverse role of platelet THBS1-boosted cycling M2 macrophages in renal injury repair and suggest platelet THBS1 as a promising therapeutic target for alleviating inflammation and kidney fibrosis.

Platelets are the terminal progeny of megakaryocytes, primarily produced in the bone marrow, and play critical roles in blood homeostasis, clotting, and wound healing. Traditionally, megakaryocytes and platelets are thought to arise from multipotent hematopoietic stem cells (HSCs) via multiple discrete progenitor populations with successive, lineage-restricting differentiation steps. However, this view has recently been challenged by studies suggesting that (1) some HSC clones are biased and/or restricted to the platelet lineage, (2) not all platelet generation follows the "canonical" megakaryocytic differentiation path of hematopoiesis, and (3) platelet output is the default program of steady-state hematopoiesis. Here, we specifically investigate the evidence that in vivo lineage tracing studies provide for the route(s) of platelet generation and investigate the involvement of various intermediate progenitor cell populations. We further identify the challenges that need to be overcome that are required to determine the presence, role, and kinetics of these possible alternate pathways.

Introduction: The platelet-to-lymphocyte ratio (PLR) is associated with the inflammatory response in various diseases. However, studies on the use of the PLR for the prognosis of elderly patients with severe trauma are lacking. In this study, we examined the relationship between the PLR and in-hospital mortality in elderly patients with severe trauma.Methods: This retrospective observational study included elderly (≥65 years) patients who were admitted for severe trauma (as defined by an Injury Severity Score [ISS] ≥ 16) between January–December 2022. We conducted multivariate analysis to assess the association between the PLR and in-hospital mortality using logistic regression of relevant covariates. We also performed receiver operating characteristic curve analysis to examine the prognostic performance of the PLR forin-hospital mortality.Results: Among the 222 patients included in the study, the in-hospital mortality rate was 19.4% (43). The PLR of non-survivors was lower than that of survivors (62.1 vs 124.5). The areas under the curve (AUC) of the Glasgow Coma Scale (GCS) score ≤12, ISS, hemoglobin level, and PLR for predicting in-hospital mortality were 0.730 (95% confidence interval [CI] 0.667–0.787), 0.771 (95% CI 0.710–0.824), 0.657 (95% CI 0.591–0.719), and 0.730 (95% CI 0.667–0.788), respectively. The AUC of the PLR was not significantly different from that of GCS score ≤12 and ISS for predicting in-hospital mortality. Multivariate analysis showed that the PLR was independently associated with in-hospital mortality (odds ratio: 0.993; 95% CI 0.987–0.999).Conclusion: Low platelet-to-lymphocyte ratio is independently associated with in-hospital mortality in elderly patients with severe trauma.

Platelet-rich plasma (PRP) has emerged as a promising therapeutic approach in regenerative medicine. It contains various growth factors and bioactive molecules that play pivotal roles in tissue repair, regeneration, and inflammation modulation. This comprehensive narrative review delves into the therapeutic potential of PRP in experimental goat and sheep research, exploring recent advancements, challenges, and future prospects in the field. PRP has been explored for its application in musculoskeletal injuries, wound healing, and orthopedic conditions. Studies have demonstrated the ability of PRP to accelerate tissue healing, reduce inflammation, and improve the overall quality of healing. Recent advancements in PRP technology have led to the development of novel formulations and delivery methods to enhance its therapeutic efficacy. PRP has shown promise in tendon and ligament injuries, osteoarthritis, and bone fractures in experimental goat and sheep research. Despite these advancements, several challenges and opportunities exist to harness the full therapeutic potential of PRP in regenerative medicine. Standardizing PRP preparation protocols, including blood collection techniques, centrifugation parameters, and activation methods, is essential to ensure consistency and reproducibility of the findings. Moreover, further research is needed to elucidate the optimal dosing, frequency, and timing of PRP administration for different clinical indications. Research conducted in goat and sheep models provides evidence supporting the translational potential of PRP in tissue engineering and regenerative medicine. By harnessing the regenerative properties of PRP and leveraging insights from preclinical studies, researchers can develop innovative therapeutic strategies to address unmet clinical needs and improve patient outcomes in diverse medical specialties. [ABSTRACT FROM AUTHOR]

The exploration of cell‐based drug delivery systems for cancer therapy has gained growing attention. Approaches to engineering therapeutic cells with multidrug loading in an effective, safe, and precise manner while preserving their inherent biological properties remain of great interest. Here, we report a strategy to simultaneously load multiple drugs in platelets in a one‐step fusion process. We demonstrate doxorubicin (DOX)‐encapsulated liposomes conjugated with interleukin‐15 (IL‐15) could fuse with platelets to achieve both cytoplasmic drug loading and surface cytokine modification with a loading efficiency of over 70 % within minutes. Due to their inherent targeting ability to metastatic cancers and postoperative bleeding sites, the engineered platelets demonstrated a synergistic therapeutic effect to suppress lung metastasis and postoperative recurrence in mouse B16F10 melanoma tumor models. [ABSTRACT FROM AUTHOR]

Existing challenges with the early diagnosis of rheumatoid arthritis (RA) and active disease, mainly by non-rheumatologists, have prompted the search for novel biomarkers. Elevations in indices derived from blood cell counts, e.g., the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR), have been reported in RA patients. However, their diagnostic accuracy has not been comprehensively assessed. Therefore, we conducted a systematic review and meta-analysis of studies reporting the sensitivity and specificity of the NLR and PLR, obtained by receiver operating characteristic (ROC) curve analysis, for the presence of RA and active disease. We searched electronic databases from inception to 15 March 2024 and assessed the risk of bias using the JBI Critical Appraisal Checklist (PROSPERO registration number: CRD42024533546). In 15 studies, the NLR exhibited acceptable accuracy for the presence of RA (area under the curve, AUC = 0.76, 95% CI 0.72 to 0.80) and active disease (AUC = 0.70, 95% CI 0.66 to 0.74). The PLR exhibited good accuracy for the presence of RA (AUC = 0.80, 95% CI 0.76 to 0.83). There were insufficient studies to assess the accuracy of the PLR for the presence of active disease. Our systematic review and meta-analysis suggests that the NLR and the PLR are promising biomarkers of RA (NLR and PLR) and active disease (NLR). Further research is required to investigate whether the NLR and PLR can significantly enhance the capacity to diagnose RA and active disease in clinical practice. [ABSTRACT FROM AUTHOR]

Depression is a common psychiatric disorder among patients undergoing maintenance haemodialysis (MHD). Depression may reportedly contribute to poor prognosis in several ways, including its effects on platelet function. We hypothesised that depression contributes to the occurrence of cardiocerebral vascular events (CCVE) and dysfunction of arteriovenous fistula (DAVF) in patients undergoing MHD through its effects on platelets. In this prospective cohort study, patients undergoing MHD were recruited and divided into depression and non-depression groups according to their Hamilton Depression Scale (HAMD) scores. The 286 enrolled patients had 103 occurrences of depressive symptoms (prevalence = 36.01%). Compared with the non-depression group, depression group had a significantly higher cumulative prevalence of CCVE and DAVF during follow-up. Cox regression analysis indicated that higher HAMD scores and lower plasma platelet distribution width (PDW) were common risk factors for CCVE and DAVF. Furthermore, HAMD scores were significantly negatively correlated with plasma PDW and was the main variable affecting changes in PDW, as indicated by multiple linear regression analysis. Depression may increase the risk of CCVE and DAVF in patients undergoing MHD by activating platelets. Plasma PDW may be a convenient indicator of platelet activation status and may predict the risk of CCVE and DAVF. [ABSTRACT FROM AUTHOR]

There is a growing interest in using extracellular vesicles (EVs) for therapeutic applications. EVs are composed of cytoplasmic proteins and nucleic acids and an external lipid bilayer containing transmembrane proteins on their surfaces. EVs can alter the state of the target cells by interacting with the receptor ligand of the target cell or by being internalised by the target cell. Blood cells are the primary source of EVs, and 1 μL of plasma contains approximately 1.5 × 107 EVs. Owing to their easy acquisition and the avoidance of cell amplification in vitro , using blood cells as a source of therapeutic EVs has promising clinical application prospects. This review summarises the characteristics and biological functions of EVs derived from different blood cell types (platelets, erythrocytes, and leukocytes) and analyses the prospects and challenges of using them for clinical therapeutic applications. In summary, blood cell-derived EVs can regulate different cell types such as immune cells (macrophages, T cells, and dendritic cells), stem cells, and somatic cells, and play a role in intercellular communication, immune regulation, and cell proliferation. Overall, blood cell-derived EVs have the potential for use in vascular diseases, inflammatory diseases, degenerative diseases, and injuries. To promote the clinical translation of blood cell-derived EVs, researchers need to perform further studies on EVs in terms of scalable and reproducible isolation technology, quality control, safety, stability and storage, regulatory issues, cost-effectiveness, and long-term efficacy. [Display omitted] • Blood contains EVs derived from platelets, erythrocytes, and leukocytes. • Blood cell-derived EVs regulate intercellular communication and immune responses. • Blood cell-derived EVs have therapeutic potential in various diseases. [ABSTRACT FROM AUTHOR]

Platelets are essential component of circulation that plays a major role in hemostasis and thrombosis. During activation and its demise, platelets release platelet‐derived microvesicles, with lysophosphatidylcholine (LPC) being a prominent component in their lipid composition. LPC, an oxidized low‐density lipoprotein, is involved in cellular metabolism, but its higher level is implicated in pathologies like atherosclerosis, diabetes, and inflammatory disorders. Despite this, its impact on platelet function remains relatively unexplored. To address this, we studied LPC's effects on washed human platelets. A multimode plate reader was employed to measure reactive oxygen species and intracellular calcium using H2DCF‐DA and Fluo‐4‐AM, respectively. Flow cytometry was utilized to measure phosphatidylserine expression, mitochondrial membrane potential (ΔΨm), and mitochondrial permeability transition pore (mPTP) formation using FITC‐Annexin V, JC‐1, and CoCl2/calcein‐AM, respectively. Additionally, platelet morphology and its ultrastructure were observed via phase contrast and electron microscopy. Sonoclot and light transmission aggregometry were employed to examine fibrin formation and platelet aggregation, respectively. The findings demonstrate that LPC induced oxidative stress and increased intracellular calcium in platelets, resulting in increased phosphatidylserine expression and reduced ΔΨm. LPC triggered caspase‐independent platelet death and mPTP opening via cytosolic and mitochondrial calcium, along with microvesiculation and reduced platelet counts. LPC increased the platelet's size, adopting a balloon‐shaped morphology, causing membrane fragmentation and releasing its cellular contents, while inducing a pro‐coagulant phenotype with increased fibrin formation and reduced integrin αIIbβ3 activation. Conclusively, this study reveals LPC‐induced oxidative stress and calcium‐mediated platelet death, necrotic in nature with pro‐coagulant properties, potentially impacting inflammation and repair mechanisms during vascular injury. [ABSTRACT FROM AUTHOR]

Background/Aim: We hypothesized that the hemoglobin, albumin, lymphocyte, and platelet (HALP) score may be a promising marker for the treatment and management of gastric cancer (GC). To test this hypothesis, we evaluated the clinical impact of the HALP score in patients with GC who received curative treatment. Patients and Methods: Consecutive patients who underwent curative resection for GC at the Yokohama City University between 2005 and 2020 were selected based on their medical records. The HALP score was calculated as follows: HALP=Hemoglobin (g/l) × albumin (g/l) × lymphocytes (109/l)/platelets (109/l). Results: The 3-year and 5-year overall survival (OS) rates were 88.6% and 85.8%, respectively, in patients with HALP scores of >40, and 70.3% and 57.2% in patients with HALP scores of ≤40. There were significant differences between the groups analyzed (p<0.001). In univariate analysis, age, T status, lymph node metastasis status, HALP score, lymphovascular invasion status, pathological type, and postoperative complication status were identified as significant prognostic factors for OS. In multivariate analysis, the HALP score remained a significant prognostic factor for OS [hazard ratio (HR)=2.679; 95% confidence interval (CI)=1.455-4.934, p=0.002]. Similar results were observed in the analysis of recurrence-free survival. In addition, the HALP score status affects the postoperative clinical course, including the occurrence of postoperative anastomotic leakage and the introduction of postoperative adjuvant chemotherapy. Conclusion: The HALP score affects both short- and long-term oncological outcomes. Thus, the HALP score may be a promising prognostic factor for the treatment and management of GC. [ABSTRACT FROM AUTHOR]

Background: Demographic and biochemical variations in newborn children as compared to adults are attributable to variable prognosis to blood transfusions. Aims of this mixed cohort study of Platelets with/without Plasma (PLT/PZ); only Plasma (PZ) transfusions in ≤ 24 months children is as follows: An Association of demography towards hospital mortality, and an association of laboratory investigations (LI) with hospital mortality. Methods: PLT/PZ (n = 72) and PZ (n = 79) children ≤ 24 months were followed up for a total length of hospital stay (LOS(D)). We calculated the Odds Ratio (OR) of demographic, and laboratory parameters for mortality, survival studies of demographic, laboratory parameters , Kaplan Meier Survival curve, Log-Rank significance (KMLR) and Multivariable regression (r2) with outcome as death. Results: The present study is in 2019–2022. Higher OR for hospital-based mortality for PLT/PZ and PZ cohort were age ≤ 1 m, weight ≤ 1500 g, preterm, gestational age ≤ 34 weeks, hospital length of stay {LOS(D)} 0–7 days, APGAR score ≤ 5, and Hb ≤ 7 g/dl. High OR, mortality was observed with Female gender, Length of stay before first transfusion {LOS(F)}, 0-7d, WHO Grade of bleeding (GOB) 4, PT>50 sec, INR>1·7, aPTT >75sec, PLT counts (μl) ≤25000/μl (PLT/PZ) and GOB 3, 4 (PZ). Higher OR for mortality was also observed with a lower derangement of coagulative parameters PT≤50s, INR ≤1·7, aPTT ≤75s (PZ). Higher survival was observed for (PLT/PZ) LOS(F) 0–7 days across age (m), weight (g) (P = 0·002; < 0·01), and INR ≤ 1·7; aPTT ≤ 75 s across LOS(D) (P < 0·01,0·018); (PZ) LOS(D) ≤ 7 days across age (m) and weight (g) (P = 0·036, 0·001); and GOB across LOS(D) (PLT/PZ; PZ) (P = 0·052, 0·005). Demography (PLT/PZ) r2 = 50·36% (P = 0·021), laboratory investigations r2 = 10·44% (P = 0·47), LOS(F) (P = 0·010), LOS(D) (P = 0·003), and GOB (P = 0·03) were the predictors. Demography (PZ) r2 (P = 0·095), investigations r2 = 8·79% (P = 0·254), LOS(D) (P = 0·026), and GOB (P = 0·012) were the predictors. Conclusions: PLT/PZ, demographic parameters, were significant cause of mortality with LOS(F), LOS(D), and GOB as predictors. PZ, demography attributed to mortality with LOS(D), and GOB as predictors. A higher OR of morality with lower derangement of laboratory profile is indicative of unnecessary transfusions in the age group. Laboratory investigations by themselves are not significant predictors of mortality. [ABSTRACT FROM AUTHOR]

Platelets play a key role in physiological hemostasis and pathological thrombosis. Based on the limitations of current antiplatelet drugs, it's important to elucidate the mechanisms of regulating platelet activation. In addition to dissolving lipid nutrients, bile acids (BAs) can regulate platelet function. However, the specific mechanisms underlying BAs‐mediated effects on platelet activation and thrombotic diseases remain unknown. Therefore, the effects of BAs on platelets and intracellular regulatory mechanisms are explored. It is showed that the inhibitory effect of secondary BAs is more significant than that of primary BAs; lithocholic acid (LCA) shows the highest inhibitory effect. In the process of platelet activation, BAs suppress platelet activation via the spleen tyrosine kinase (SYK), protein kinase B (Akt), and extracellular signal‐regulated kinase1/2 (Erk1/2) pathways. Nck adaptor proteins (NCK1) deficiency significantly suppress the activity of platelets and arterial thrombosis. Phosphorylated proteomics reveal that LCA inhibited phosphorylation of syntaxin‐11 at S80/81 in platelets. Additional LCA supplementation attenuated atherosclerotic plaque development and reduced the inflammation in mice. In conclusion, BAs play key roles in platelet activation via Syk, Akt, ERK1/2, and syntaxin‐11 pathways, which are associated with NCK1. The anti‐platelet effects of BAs provide a theoretical basis for the prevention and therapy of thrombotic diseases. [ABSTRACT FROM AUTHOR]

Objective: Several pathological conditions trigger the formation of microvesicles (MVs), including infectious diseases such as COVID-19. The shedding of MVs increases the levels of inflammatory factors (e.g., interleukin-6; IL-6) and ultimately leads to an inflammatory cascade response, while also increasing the procoagulant response. The current study aimed to evaluate the level of circulating MVs and their procoagulant activity as well as the serum level of IL-6 in patients with COVID-19 and healthy controls. In this case-control study, 65 patients with COVID-19 and 30 healthy individuals were sampled after obtaining written informed consent. MVs counting was measured using conjugated CD61, CD45, CD235a, and Annexin-V antibodies. Additionally, the procoagulant activity of MVs and the IL-6 level were estimated using enzyme-linked immunosorbent assay (ELISA). Results: The majority of MVs were platelet-derived MVs (PMVs). Patients with COVID-19 had significantly higher levels of MVs, procoagulant MVs, and IL-6 compared to healthy controls (p < 0.001). MVs were significantly correlated with procoagulant MVs, D-Dimer levels, fibrinogen, and IL-6, but not with platelet, lymphocyte, and neutrophil counts. Conclusion: Elevated levels of procoagulant MVs and their association with inflammatory and coagulation markers in patients with COVID-19 are suggested as a novel circulatory biomarker to evaluate and predict the procoagulant activity and severity of COVID-19. [ABSTRACT FROM AUTHOR]

Background: Protease-activated receptor 1 (PAR1) is expressed in human platelets and can be activated by low concentrations of thrombin. Vorapaxar, a selective antagonist of PAR1, inhibits thrombin-induced calcium mobilization in human platelet, which is associated with an increased risk of bleeding. Conversely, the administration of a positive allosteric modulator (PAM) of PAR1 may pose a substantial risk of thrombosis due to inducing excessive platelet activation. In this study, we discovered a novel PAM of PAR1 and investigated the effect of enhanced PAR1 activation by PAM of PAR1 on platelet activation. Methods: To find PAMs of PAR1, a cell-based screen was performed in HT29 cells, and finally, gestodene, an oral contraceptive drug (OC), was identified as a novel PAM of PAR1. The mechanism of action of gestodene and its effects on platelet activation were investigated in human megakaryocytic leukemia cell line MEG-01 cells and human platelet. Results: Gestodene enhanced both thrombin- and PAR1-activating peptide (AP)- induced intracellular calcium levels in a dose-dependent manner without altering PAR2 and PAR4 activity. Gestodene significantly increased PAR1-AP-induced internalization of PAR1 and phosphorylation of ERK1/2, and the enhancing effects were significantly blocked by vorapaxar. Furthermore, gestodene potently increased PAR1-AP induced morphological changes in MEG-01 cells. Remarkably, in human blood, gestodene exerted a robust augmentation of PAR1-AP-induced platelet aggregation, and vorapaxar effectively attenuated the gestodene-induced enhancement of platelet aggregation mediated by PAR1. Conclusion: Gestodene is a selective PAM of PAR1 and suggest one possible mechanism for the increased risk of venous thromboembolism associated with OCs containing gestodene. [ABSTRACT FROM AUTHOR]

Introduction: Platelet transfusion is a standard treatment to prevent bleeding in patients with hematological malignancies. Although transfusions can improve platelet count, their impact on platelet function remains controversial. Methods: We conducted flow cytometry to assess platelet function before and after transfusion and performed subgroup analyses to examine differences based on blood type, corrected count increment (CCI), and platelet microparticles. Results: Overall, 50 patients who received prophylactic platelet transfusion were enrolled. CD42b expression increased, whereas CD41 expression decreased after transfusion. Apheresis platelets exhibited the lowest expression of PAC‐1 and P‐selectin when exposed to agonist stimulations. PAC‐1 expression increased under high adenosine diphosphate (ADP) stimulation, while P‐selectin expression increased under both high ADP and thrombin receptor‐activating peptide stimulation. In the subgroup analysis, patients with a CCI >4500 and those with the same blood types exhibited a more significant increase in PAC‐1 and P‐selectin expression under agonist stimulation. When comparing apheresis platelets collected on different days, only the percentage of platelet‐derived microparticles showed a significant increase. Conclusion: Prophylactic transfusion improved platelet function. Platelet function significantly improved in patients with a CCI >4500, those with the same blood types as that of apheresis platelets, or those with platelet‐derived microparticle levels <4.7%. No significant improvement in platelet function was noted after the transfusion of different blood types with acceptable compatibility or the transfusion of incompatible blood types. Our results suggest that transfusing platelets with the same blood type remains the optimal choice. [ABSTRACT FROM AUTHOR]

AbstractIn the process of the drug development, studies on the cytochrome P450 (CYP) profiles after its administration provided fundamental information regarding drug interactions with concomitantly administered drugs. Here, we evaluated the influence of the administration of H12-(ADP)-liposomes, a platelet substitute, on the mRNA and protein expression, and metabolic activity of CYPs, with focus on the CYP1A2, CYP2C11 and CYP3A2, in rat liver.At 24 h after administering saline or H12-(ADP)-liposomes (10 mg of lipids/kg), a quantitative RT-PCR and western blot analysis revealed that the mRNA and proteins expression of all of the target hepatic CYP isoforms were not different between the saline and H12-(ADP)-liposome groups. Furthermore, an ex vivo CYP metabolic activity assay showed that hepatic CYP metabolic activities in the H12-(ADP)-liposome group were comparable to the corresponding saline group. On the other hand, the area under the blood concentration-time curve for substitutes for CYP1A2 and CYP2C11 was higher in H12-(ADP)-liposome group than in saline group, but the degree of elevations was negligible levels.At a minimum, based on these results, we conclude that H12-(ADP)-liposomes have no quantitative and qualitative effect on the hepatic CYP isoforms, indicating that the drug interactions of H12-(ADP)-liposomes with CYP-metabolizing drugs would be negligible.In the process of the drug development, studies on the cytochrome P450 (CYP) profiles after its administration provided fundamental information regarding drug interactions with concomitantly administered drugs. Here, we evaluated the influence of the administration of H12-(ADP)-liposomes, a platelet substitute, on the mRNA and protein expression, and metabolic activity of CYPs, with focus on the CYP1A2, CYP2C11 and CYP3A2, in rat liver.At 24 h after administering saline or H12-(ADP)-liposomes (10 mg of lipids/kg), a quantitative RT-PCR and western blot analysis revealed that the mRNA and proteins expression of all of the target hepatic CYP isoforms were not different between the saline and H12-(ADP)-liposome groups. Furthermore, an ex vivo CYP metabolic activity assay showed that hepatic CYP metabolic activities in the H12-(ADP)-liposome group were comparable to the corresponding saline group. On the other hand, the area under the blood concentration-time curve for substitutes for CYP1A2 and CYP2C11 was higher in H12-(ADP)-liposome group than in saline group, but the degree of elevations was negligible levels.At a minimum, based on these results, we conclude that H12-(ADP)-liposomes have no quantitative and qualitative effect on the hepatic CYP isoforms, indicating that the drug interactions of H12-(ADP)-liposomes with CYP-metabolizing drugs would be negligible. [ABSTRACT FROM AUTHOR]

Previous literature suggests that sphingolipids may impact systemic coagulation and platelet aggregation, thus modulating the risks of thrombotic events. The goal of this investigation was to evaluate the role of serum sphingolipids on intrinsic platelet function to assess whether pharmacologic manipulation of sphingolipid metabolites would impact platelet aggregability. C57BL/6J mice were injected with either normal saline, 1 mg/kg FTY720 (synthetic sphingosine-1-phosphate [S1P] receptor analog), or 5 mg/kg SLM6031434 (sphingosine kinase two inhibitor). Mice were sacrificed at 6 h and whole blood (WB) was collected for impedance aggregometry assessing platelet responsiveness to arachidonic acid or adenosine diphosphate. Ex vivo studies utilized WB or platelet-rich plasma that was pretreated with S1P, FTY720, amitriptyline, or d-sphingosine then analyzed by aggregability and flow cytometry for platelet and platelet-derived microvesicle characteristics. FTY720 and SLM6031434 pretreated induced similar arachidonic acid and adenosine diphosphate–mediated platelet aggregation as controls. Ex vivo WB and platelet-rich plasma treatment with S1P, FTY720, amitriptyline and d-sphingosine did not impact platelet aggregation. The percentages of CD41+, CD62P+ and CD41+/ceramide+, CD62P+/ceramide + platelets, and platelet-derived microvesicle were not significantly different between amitriptyline-treated and normal saline-treated cohorts. Sphingolipid modulating agents, such as FTY720, SLM6031434, S1P, amitriptyline, ceramide, and d-sphingosine do not appear to independently impact platelet aggregation in murine models. [ABSTRACT FROM AUTHOR]

Several investigations are being done to increase the short lifetime of mesenchymal stem cells (MSCs). One of the crucial genes involved in the immortalization of MSCs, hTERT (human telomerase reverse transcriptase), is activated in most publications using viral-based techniques. In this work, we investigated the use of platelet-derived (PMPs) and B cell precursor leukemia-derived microparticles as a nonviral method to trigger and compare the expression of the hTERT gene in MSCs. MSCs were extracted from the umbilical cord for the current investigation and identified using a flow cytometry approach and an inverted microscope. The Nalm-6 cell line and platelet concentrate were used to isolate microparticles (MPs). MSCs and MPs were cocultured for 14 days at 25-, 50-, and 100 μg/ml concentrations. qRT-PCR was used to research the expression of the hTERT gene. SPSS 26.0's t test was used to compare the outcomes. After coculture with platelet MPs, MSCs had higher levels of hTERT gene expression than the control group. In contrast, this gene's expression was concurrently decreased in MSCs exposed to MPs generated from Nalm-6. We demonstrated that following 14-day treatment, PMP significantly boosted the hTERT gene expression in MSCs, while the Nalm-6 MPs lowered the gene expression. However, additional studies are necessary due to the stability of hTERT gene expression and the immortalization of MSCs following exposure. [ABSTRACT FROM AUTHOR]

Background: Erectile dysfunction (ED) is associated with inflammation. The systematic immune‐inflammation index (SII), as a new inflammation marker, was applied to predict the risk of diseases. However, no research explores the relationship between SII and ED. Hence, the purpose of this study was to investigate the association between SII and ED. Methods: Related data were obtained from the National Health and Nutrition Examination Survey (NHANES) 2001−2004. Based on self‐report, all participants were classified into ED and non‐ED group. Weighted multivariate regression analysis the relationship between categorical SII and ED in unadjusted and adjusted models. Restricted cubic spline (RCS) was used to examine the association of continuous SII and ED risk. Furthermore, the association between categorical SII and the risk of ED was evaluated among subgroups of age, body mass index, hypertension, diabetes and cardiovascular disease. Finally, weighted multivariate regression analysis and RCS were performed to assessed the connection between SII and the risk of severe ED. Results: Initially, data on 21,161 participants were obtained. After implementing the inclusion and exclusion criteria, 3436 participants were included in analyses. Weighted multivariate regression analysis demonstrated that Q4 group SII was associated with an increased risk of ED (OR = 1.03, 95% confidence intervals: 1.00−1.05, p =.03). RCS showed SII was nonlinearly associated with the risk of ED, and the inflection point of SII was at 485.530. In addition, subgroup analyses demonstrated that participants in the SII > 485.530 group had a higher ED risk than SII ≤ 485.530 group among subgroups of age ≥50, hypertension, and non‐diabetes. Weighted multivariate regression analysis and RCS found no relationship of SII and the risk of severe ED. Conclusion: In US adults, SII > 485.530 was correlated with an increased risk of ED. While, no significant association between SII and severe ED risk. Additional studies are required to support our results. [ABSTRACT FROM AUTHOR]

Tumor metastasis, the apex of cancer progression, poses a formidable challenge in therapeutic endeavors. Circulating tumor cells (CTCs), resilient entities originating from primary tumors or their metastases, significantly contribute to this process by demonstrating remarkable adaptability. They survive shear stress, resist anoikis, evade immune surveillance, and thwart chemotherapy. This comprehensive review aims to elucidate the intricate landscape of CTC formation, metastatic mechanisms, and the myriad factors influencing their behavior. Integral signaling pathways, such as integrin-related signaling, cellular autophagy, epithelial-mesenchymal transition, and interactions with platelets, are examined in detail. Furthermore, we explore the realm of precision nanomedicine design, with a specific emphasis on the anoikis‒platelet interface. This innovative approach strategically targets CTC survival mechanisms, offering promising avenues for combatting metastatic cancer with unprecedented precision and efficacy. The review underscores the indispensable role of the rational design of platelet-based nanomedicine in the pursuit of restraining CTC-driven metastasis. This review emphasizes the vital role of platelet-based nanomedicine design aiming to target the anoikis–platelet interface in restraining circulating tumor-cell metastasis. [Display omitted] [ABSTRACT FROM AUTHOR]

The microvasculature, which makes up the majority of the cardiovascular system, plays a crucial role in the process of thrombosis, with the pathological formation of blood clots inside blood vessels. Since blood microflow conditions significantly influence platelet activation and thrombosis, accurately mimicking the structure of bifurcating microvascular networks and emulating local physiological blood flow conditions are valuable for understanding blood clot formation. In this work, we present an in vitro model for blood clotting in microvessels, focusing on 3D bifurcations that align with Murray's law, which guides vascular networks by maintaining a constant wall shear rate throughout. Using these models, we demonstrate that microvascular bifurcations act as sites facilitating thrombus formation compared to straight models. Additionally, by culturing endothelial cells on the luminal surfaces of the models, we show the potential of using our in vitro platforms to recapitulate the initial clotting in diseases involving endothelial dysfunction, such as Thrombotic Thrombocytopenic Purpura. [ABSTRACT FROM AUTHOR]

Extracellular vesicles (EVs) are crucial for transferring bioactive materials between cells and play vital roles in both health and diseases. Cellular protrusions, including filopodia and microvilli, are generated by the bending of the plasma membrane and are considered to be rigid structures facilitating various cellular functions, such as cell migration, adhesion, and environment sensing. Compelling evidence suggests that these protrusions are dynamic and flexible structures that can serve as sources of a new class of EVs, highlighting the unique role they play in intercellular material transfer. Cytonemes are specialized filopodia protrusions that make direct contact with neighboring cells, mediating the transfer of bioactive materials between cells through their tips. In some cases, these tips fuse with the plasma membrane of neighboring cells, creating tunneling nanotubes that directly connect the cytosols of the adjacent cells. Additionally, virus particles can be released from infected cells through small bud-like of plasma membrane protrusions. These different types of protrusions, which can transfer bioactive materials, share common protein components, including I-BAR domain-containing proteins, actin cytoskeleton, and their regulatory proteins. The dynamic and flexible nature of these protrusions highlights their importance in cellular communication and material transfer within the body, including development, cancer progression, and other diseases. [ABSTRACT FROM AUTHOR]

Based on a wealth of evidence, aspirin is one of the cornerstones of secondary prevention of cardiovascular disease. However, despite several studies showing efficacy also in primary prevention, an unopposed excess risk of bleeding leading to a very thin safety margin is evident in subjects without a clear acute cardiovascular event. Overall, the variability in recommendations from different scientific societies for aspirin use in primary prevention is a classic example of failure of simple risk stratification models based on competing risks (atherothrombosis vs. bleeding), perceived to be opposed but intertwined at the pathophysiological level. Notably, cardiovascular risk is dynamic in nature and cannot be accurately captured by scores, which do not always consider risk enhancers. Furthermore, the widespread use of other potent medications in primary prevention, such as lipid-lowering and anti-hypertensive drugs, might be reducing the benefit of aspirin in recent trials. Some authors, drawing from specific pathophysiological data, have suggested that specific subgroups might benefit more from aspirin. This includes patients with diabetes and those with obesity; sex-based differences are considered as well. Moreover, molecular analysis of platelet reactivity has been proposed. A beneficial effect of aspirin has also been demonstrated for the prevention of cancer, especially colorectal. This review explores evidence and controversies concerning the use of aspirin in primary prevention, considering new perspectives in order to provide a comprehensive individualized approach. [ABSTRACT FROM AUTHOR]

Background and Purpose Experimental Approach Key Results Conclusion and Implications Although the amphiphilic nature of the widely used antithrombotic drug Ticagrelor is well known, it was never considered as a membranotropic agent capable of interacting with the lipid bilayer in a receptor‐independent way. In this study, we investigated the influence of Ticagrelor on plasma membrane lipid order in platelets and if this modulates the potency of Ticagrelor at the P2Y12 receptor.We combined fluorescent in situ, in vitro and in silico approaches to probe the interactions between the plasma membrane of platelets and Ticagrelor. The influence of Ticagrelor on the lipid order of the platelet plasma membrane and large unilamellar vesicles was studied using the advanced fluorescent probe NR12S. Furthermore, the properties of model lipid bilayers in the presence of Ticagrelor were characterized by molecular dynamics simulations. Finally, the influence of an increased lipid order on the dose‐response of platelets to Ticagrelor was studied.Ticagrelor incorporates spontaneously into lipid bilayers and affects the lipid order of the membranes of model vesicles and isolated platelets, in a nontrivial composition and concentration‐dependent manner. We showed that higher plasma membrane lipid order in platelets leads to a lower IC50 value for Ticagrelor. It is shown that membrane incorporation of Ticagrelor increases its potency at the P2Y12 receptor, by increasing the order of the platelet plasma membrane.A novel dual mechanism of Ticagrelor action is suggested that combines direct binding to P2Y12 receptor with simultaneous modulation of receptor‐lipid microenvironment. [ABSTRACT FROM AUTHOR]

Background and Aims The pathways and metabolites that contribute to residual cardiovascular disease risks are unclear. Low-calorie sweeteners are widely used sugar substitutes in processed foods with presumed health benefits. Many low-calorie sweeteners are sugar alcohols that also are produced endogenously, albeit at levels over 1000-fold lower than observed following consumption as a sugar substitute. Methods Untargeted metabolomics studies were performed on overnight fasting plasma samples in a discovery cohort (n = 1157) of sequential stable subjects undergoing elective diagnostic cardiac evaluations; subsequent stable isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses were performed on an independent, non-overlapping validation cohort (n = 2149). Complementary isolated human platelet, platelet-rich plasma, whole blood, and animal model studies examined the effect of xylitol on platelet responsiveness and thrombus formation in vivo. Finally, an intervention study was performed to assess the effects of xylitol consumption on platelet function in healthy volunteers (n = 10). Results In initial untargeted metabolomics studies (discovery cohort), circulating levels of a polyol tentatively assigned as xylitol were associated with incident (3-year) major adverse cardiovascular event (MACE) risk. Subsequent stable isotope dilution LC-MS/MS analyses (validation cohort) specific for xylitol (and not its structural isomers) confirmed its association with incident MACE risk [third vs. first tertile adjusted hazard ratio (95% confidence interval), 1.57 (1.12–2.21), P <.01]. Complementary mechanistic studies showed xylitol-enhanced multiple indices of platelet reactivity and in vivo thrombosis formation at levels observed in fasting plasma. In interventional studies, consumption of a xylitol-sweetened drink markedly raised plasma levels and enhanced multiple functional measures of platelet responsiveness in all subjects. Conclusions Xylitol is associated with incident MACE risk. Moreover, xylitol both enhanced platelet reactivity and thrombosis potential in vivo. Further studies examining the cardiovascular safety of xylitol are warranted. [ABSTRACT FROM AUTHOR]

The platelet/high-density lipoprotein ratio (PHR) has been identified as a significant indicator of inflammation and a hypercoagulable state, demonstrating a strong link with the severity of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS). However, its correlation with hyperuricemia has not yet been documented. This study utilized a cross-sectional design, analyzing data collected from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016 in the United States. The platelet/high-density lipoprotein ratio (PHR) was determined by dividing the number of platelets (PLT) by the level of high-density lipoprotein cholesterol (HDL-C). We employed multivariable logistic regression analyses, generalized additive models, and subgroup analyses to investigate the correlation between PHR and hyperuricemia. The study revealed a hyperuricemia prevalence of 18.56%. Analysis indicated a significant positive correlation between PHR and the risk of hyperuricemia (OR 1.11, 95% CI 1.08, 1.14). This correlation remained consistent across different subgroups including age, ethnicity, gender, and body mass index (BMI). Smooth curve fitting demonstrated a saturation effect between PHR and the risk of hyperuricemia. PHR is positively correlated with hyperuricemia and may serve as a novel biomarker for predicting the onset of this condition. Additionally, targeted interventions to improve PHR might help reduce the incidence of hyperuricemia. [ABSTRACT FROM AUTHOR]

Background: Hyperactive neutrophil extracellular traps (NETs) formation plays a crucial role in active severe systemic lupus erythematosus (SLE). However, what triggers the imbalance in dysregulated NETs formation in SLE is elusive. Transfer RNA-derived small RNAs (tsRNAs) are novel non-coding RNAs, which participate in various cellular processes. We explore the role of tsRNAs on NETs formation in SLE. Methods: We analyzed the levels of NETs DNA and platelet-derived extracellular vesicles (pEVs) from 50 SLE patients and 20 healthy control subjects. The effects of pEVs on NETs formation were evaluated by using immunofluorescence assay and myeloperoxidase-DNA PicoGreen assay. The regulatory mechanism of pEVs on NETs formation and inflammatory cytokines production were investigated using an in vitro cell-based assay. Results: Increased circulating NETs DNA and pEVs were shown in SLE patients and were associated with disease activity (P < 0.005). We demonstrated that SLE patient-derived immune complexes (ICs) induced platelet activation, followed by pEVs release. ICs-triggered NETs formation was significantly enhanced in the presence of pEVs through Toll-like receptor (TLR) 8 activation. Increased levels of tRF-His-GTG-1 in pEVs and neutrophils of SLE patients were associated with disease activity. tRF-His-GTG-1 interacted with TLR8 to prime p47phox phosphorylation in neutrophils, resulting in reactive oxygen species production and NETs formation. Additionally, tRF-His-GTG-1 modulated NF-κB and IRF7 activation in neutrophils upon TLR8 engagement, resulting IL-1β, IL-8, and interferon-α upregulation, respectively. Conclusions: The level of tRF-His-GTG-1 was positively correlated with NETs formation in SLE patients; tRF-His-GTG-1 inhibitor could efficiently suppress ICs-triggered NETs formation/hyperactivation, which may become a potential therapeutic target. Plain English summary: Neutrophils and platelets are key members in the immunopathogenesis of SLE. EVs play a key role in intercellular communication. Abnormal NETs formation promotes vascular complications and organ damage in SLE patients. tsRNA is a novel regulatory small non-coding RNA and participates in diverse pathological processes. Herein, we showed that SLE patient-derived ICs activates platelets directly, followed by intracellular tRF-His-GTG-1 upregulation, which is loaded into pEVs. The pEV-carried tRF-His-GTG-1 could interact with TLR8 in neutrophils, followed by activation of the downstream signaling pathway, including p47phox-NOX2-ROS, which causes NETs enhancement, while IRF7 promotes the expression of IFN-α. The tRF-His-GTG-1 inhibitor could suppress efficiently SLE ICs-induced NETs formation and pEVs primed NETs enhancement. This study offers new molecular machinery to explain the association between the platelets-derived tsRNAs, pEVs, and hyperactive NETs formation in lupus. tRF-His-GTG-1 may serve as a potential therapeutic target and help to advance our understanding of tsRNAs in SLE pathogenesis. [ABSTRACT FROM AUTHOR]

Objectives: Neutrophil/lymphocyte ration (NLR) and platelet/lymphocyte ratio (PLR) levels can be used as systemic infallamotory parameters. Asymmetric dimethyl arginine (ADMA) inhibits endothelial nitric oxide synthase. Phase Angle (PhA) is a potential paremeter to screen for inflammatory abnormalities. In present study we aimed to determine the relations between NLR, PLR, ADMA, and PhA in terms of early markers for nutritonal status in addition to their well-known role in inflammation. Methods: A total of 89 patients undergoing maintenance hemodialysis 3 days a week at least 6 months were enrolled. To assess nutritional status, we performed the dietary questionnaire and mini nutritional assessment score (MNAS). ADMA was measured by ELISA. NLR and PLR are calculated from monthly complete blood count tests. Patients were divided into 2 groups accordng to NLR levels as group 1 (NLR ≥ 4.6; n=48) ve and group 2 (NLR<4.6, n=41). Results: The mean ADMA level was 0.03±0.01 µmol/L, the mean PhA was 7.2 ± 1.1°. In subgroup analysis, MNAS, albumin levels and phase angle of patients in group 1 were lower and CRP, PLR, ADMA levels were higher when compared to group 2. In correlation analysis, NLO was positively correlated with PLR, CRP and ADMA however negatively correlated with albumin and PhA levels. In regression analysis, NLR, PLR and ADMA were detected as independent predictors of MNAS. Conclusion: In conclusion our study suggests that NLR, PLR and ADMA are independent predictors for nutritional status and inflammation in patients ongoing hemodialysis. [ABSTRACT FROM AUTHOR]

Introduction: To determine a cut-off value for systemic immune-inflammation index (SII) (neutrophil × platelet/lymphocyte) in the prediction of fetal growth restriction (FGR). Materials and methods: This case–control study was conducted retrospectively at the Obstetrics-Gynecology and Perinatology Clinics of Etlik Zubeyde Hanim Women's Health Education and Training Hospital. Singleton pregnant women with late-onset FGR who were followed up in outpatient clinics or hospitalized and whose pregnancy resulted at our hospital were included in the study group (group I). Healthy early and full-term singleton pregnant women with spontaneous labor who were followed up in the same hospital and whose pregnancy resulted at the same hospital were included in the control group (group II). Receiver-operating characteristic curves were used to assess the performance of SII value in predicting FGR. Results: We recruited 79 cases (pregnant with late-onset fetal growth restriction) and 79 controls (healthy pregnant), matched for age, body mass index, and parity. ΔSII was statistically significantly higher in the pregnant with late-onset FGR compared with healthy pregnant (123 vs − 65; p = 0.039). The values in ROC curves with the best balance of sensitivity/specificity were > 152 109/L (49% sensitivity, 70% specificity) and > 586 109/L (27% sensitivity, 90% specificity) for late-onset FGR. Discussion: Higher ΔSII levels in maternal blood indicate an inflammatory process causing FGR. The cut-off value for ΔSII (> 586 109/L) at 90% specificity can be used as a screening test. In the presence of ΔSII levels > 586 109/L (27% sensitivity and 90% specificity), the physicians should be more cautious about risk for FGR. Therefore, pregnant women at risk for FGR should be checked more frequently and monitored closely. However, further studies are needed to confirm our findings. [ABSTRACT FROM AUTHOR]

Management of immune thrombocytopenia (ITP) in dogs and cats is evolving, but there are no evidence‐based guidelines to assist clinicians with treatment decisions. Likewise, the overall goals for treatment of ITP have not been established. Immunosuppressive doses of glucocorticoids are the first line treatment, but optimal treatment regimens beyond glucocorticoids remain uncertain. Additional options include secondary immunosuppressive drugs such as azathioprine, modified cyclosporine, and mycophenolate mofetil, usually selected based on clinician preference. Vincristine, human IV immunoglobulin (hIVIg), and transfusion of platelet or red blood cell–containing products are often used in more severe cases. Splenectomy and thrombopoietin receptor agonists are usually reserved for refractory cases, but when and in which patient these modalities should be employed is under debate. To develop evidence‐based guidelines for individualized treatment of ITP patients, we asked 20 Population Intervention Comparison Outcome (PICO) format questions. These were addressed by 17 evidence evaluators using a literature pool of 288 articles identified by a structured search strategy. Evidence evaluators, using panel‐designed templates and data extraction tools, summarized evidence and created guideline recommendations. These were integrated by treatment domain chairs and then refined by iterative Delphi survey review to reach consensus on the final guidelines. In addition, 19 non‐PICO questions covering scenarios in which evidence was lacking or of low quality were answered by expert opinion using iterative Delphi surveys with panelist integration and refinement. Commentary was solicited from multiple relevant professional organizations before finalizing the consensus. The rigorous consensus process identified few comparative treatment studies, highlighting many areas of ITP treatment requiring additional studies. This statement is a companion manuscript to the ACVIM Consensus Statement on the Diagnosis of Immune Thrombocytopenia in Dogs and Cats. [ABSTRACT FROM AUTHOR]

Immune thrombocytopenia (ITP) is the most common acquired primary hemostatic disorder in dogs. Immune thrombocytopenia less commonly affects cats but is an important cause of mortality and treatment‐associated morbidity in both species. Immune thrombocytopenia remains a diagnosis of exclusion for which diagnostic guidelines are lacking. Primary, or non‐associative, ITP refers to autoimmune platelet destruction. Secondary, or associative, ITP arises in response to an underlying disease trigger. However, evidence for which comorbidities serve as ITP triggers has not been systematically evaluated. To identify key diagnostic steps for ITP and important comorbidities associated with secondary ITP, we developed 12 Population Evaluation/Exposure Comparison Outcome (PECO) format questions. These questions were addressed by evidence evaluators utilizing a literature pool of 287 articles identified by the panelists using a structured search strategy. Evidence evaluators, using panel‐designed templates and data extraction tools, summarized evidence and created guideline recommendations that then were integrated by diagnosis and comorbidity domain chairs. The revised PECO responses underwent a Delphi survey process to reach consensus on final guidelines. A combination of panel expertise and PECO responses were employed to develop algorithms for diagnosis of ITP in dogs and cats, which also underwent 4 iterations of Delphi review. Comorbidity evidence evaluators employed an integrated measure of evidence (IME) tool to determine evidence quality for each comorbidity; IME values combined with evidence summaries for each comorbidity were integrated to develop ITP screening recommendations, which also were subjected to Delphi review. Commentary was solicited from multiple relevant professional organizations before finalizing the consensus. The final consensus statement provides clinical guidelines for the diagnosis of, and underlying disease screening for, ITP in dogs and cats. The systematic consensus process identified numerous knowledge gaps that should guide future studies. This statement is a companion manuscript to the ACVIM Consensus Statement on the Treatment of Immune Thrombocytopenia. [ABSTRACT FROM AUTHOR]

Background and Objectives: Platelet transfusions are increasing with medical advances. Based on FDA criteria, platelet units are assessed by in vitro measures; however, it is not known how platelet processing and storage duration affect function in vivo. Our study's aim was to develop a novel platelet transfusion model stored in mouse plasma that meets FDA criteria adapted to mice, and transfused fresh and stored platelets are detectable in clots in vivo. Study Design and Methods: Platelet units stored in mouse plasma were prepared using a modified platelet‐rich plasma (PRP) collection protocol. Characteristics of fresh and stored units, including pH, cell count, in vitro measures of activity, including activation and aggregation, and post‐transfusion recovery (PTR), were determined. Lastly, a tail transection assay was conducted using mice transfused with fresh or stored units, and transfused platelets were identified by confocal imaging. Results: Platelet units had acceptable platelet and white cell counts and were negative for bacterial contamination. Fresh and 1‐day stored units had acceptable pH; the platelets were activatable by thrombin and adenosine diphosphate, agreeable with thrombin, had acceptable PTR, and were present in vivo in clots of recipients after tail transection. In contrast, 2‐day stored units had clinically unacceptable quality. Conclusion: We developed mouse platelets for transfusion analogous to human platelet units using a modified PRP collection protocol with maximum storage of 1 day for an 'old' unit. This provides a powerful tool to test how process modifications and storage conditions affect transfused platelet function in vivo. [ABSTRACT FROM AUTHOR]

Purpose: Inflammation is thought to be a vital element in the etiology of cancer-related fatigue (CRF), and circulating blood cell parameters could be important markers of inflammatory response. However, the associations of several major blood cell counts and their derived inflammatory indices with CRF are not well described. The present study aimed to establish whether a relationship exists between the counts of three white blood cell (WBC) types, platelets, and CRF and investigate whether several systemic inflammatory indices were associated with CRF in patients with breast cancer (BC). Methods: A cross-sectional survey was conducted with a sample of 824 patients with BC undergoing chemotherapy. The cancer fatigue scale was administered to assess CRF. Hematological indicators, including neutrophils, lymphocytes, monocytes, and platelets, were retrieved from routine blood test. Network analyses were used to examine the associations among them. Results: Among 824 participants, the mean score of CRF was (27 ± 10), ranging from 0 to 57. The results of network models indicated that physical fatigue was negatively linked to lymphocyte counts (weight = − 0.161), and affective fatigue was positively associated with neutrophil counts (weight = 0.070). Additionally, physical fatigue was positively linked to the platelet-to-lymphocyte ratio (PLR) (weight = 0.049). Conclusion: There were preliminary associations of counts of three WBC types, platelet counts, and systemic inflammatory indices, with distinct dimensions of CRF in patients with BC. Findings provide empirical support for the cellular basis of fatigue-associated inflammatory states. [ABSTRACT FROM AUTHOR]

This systematic review and meta-analysis aim to establish associations between metabolic syndrome (MetS) and erythrocyte and platelet markers, contributing to improved diagnostic tests for identifying individuals at risk. Observational studies and Randomized Controlled Trials (RCTs) were included. The standardized mean difference (SMD) and 95% confidence intervals (CI) of erythrocyte and platelet markers between individuals with and without MetS were used as effect size (inverse variance model). Methodological quality assessment was conducted using the Newcastle-Ottawa scale (NOS) for observational studies and the Cochrane Risk of Bias tool 2.0 for RCTs. The analysis included 51 articles. Compared to controls, individuals with MetS exhibited significantly higher concentrations of mean red blood cell count [Standardized Mean Difference (95% CI): 0.15 (0.13−0.18); p<0.00001], hemoglobin [0.24 (0.18−0.31); p<0.00001], blood platelet count [5.49 (2.78–8.20); p<0.0001], and red blood cell distribution width [(0.55 (0.05–1.04); p=0.03]. Regarding mean platelet volume [0.16 (– 0.03 to 0.35); p=0.10] and platelet-to-lymphocyte ratio (PLR) [7.48 (–2.85–17.81); p=0.16], a non-significant difference was observed in patients with MetS. There was no statistically significant difference in hematocrit counts between the two groups [0.47 (–0.40 to –1.34); p=0.29]. Biomarkers such as mean red blood cell count, hemoglobin, blood platelet count, and RDW are associated with higher levels in patients in MetS, whereas mean platelet volume and PLR tend to be lower. These markers can potentially provide new avenues for early diagnosis of MetS. [ABSTRACT FROM AUTHOR]

Objective: As patients with acute-phase familial Mediterranean fever (FMF) require prompt diagnosis for optimal management, we are conducting a study to compare inflammatory markers during the attack and silent phases in individuals referred to the emergency department. Methods: This case-control study involved 184 FMF patients under 16 years old, with data collected at Bo Ali Hospital's emergency department in Ardabil city throughout 2022. Patients in the attack phase were assessed by emergency medicine specialists, while those in the silent phase were recruited fromthe rheumatology clinic. Hematological parameters were obtained from venous blood samples, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and red blood cell distribution width (RDW) were calculated. Statistical analyses included 1-Sample Kolmogorov-Smirnov, ANOVA, Tukey's-b post hoc, Independent Samples T-test, Kruskal-Wallis, and Pearson Chi-squared tests. Results: In the attack group, the NLR correlated with increased leukocytes (r=0.652, P<0.001) and RDW(r=0.310, P=0.003). The non-attack group showed a correlation between the NLR and higher leukocytes (r=0.384, P<0.001) and ESR (r=0.214, P=0.04). Additionally, the attack group exhibited a correlation between the PLR and higher leukocytes (r=0.711, P=0.009), and ESR (r=0.285, P=0.014) while no correlation was found in the non-attack group. Conclusion: Our study revealed that RDW levels were significantly higher in FMF patients, indicating clinical inflammation. During FMF attacks, NLR and PLR ratios were notably elevated, making them key markers for systemic inflammation in these patients. [ABSTRACT FROM AUTHOR]

Platelets engage in HIV-1 infection by interacting with immune cells, which has been realized broadly. However, the potential interaction between platelets and CD8+ T cells remains unidentified. Here, treatment-naive individuals with HIV-1, complete immunological responders to antiretroviral therapy, and healthy controls were enrolled. First, we found that treatment-naive individuals with HIV-1 had low platelet numbers and high CD8+ T-cell counts when compared with complete immunological responders to antiretroviral therapy and healthy controls, leading to a low platelet/CD8+ T-cell ratio in peripheral blood, which could effectively differentiate the status of HIV-1 infection. Moreover, cytokines that may have been derived from platelets were higher in the plasma of people with HIV-1 despite viral suppression. Furthermore, we demonstrated that platelet–CD8+ T-cell aggregates were elevated in treatment-naive individuals with HIV-1, which positively correlated with HIV-1 viral load but negatively correlated with CD4+ T-cell count and CD4/CD8 ratio. Finally, we revealed that platelet–CD8+ T-cell aggregates correlate with enhanced activation/exhaustion and pyroptosis/apoptosis compared with free CD8+ T cells. Moreover, platelet-induced caspase 1 activation of CD8+ T cells correlated with IL-1β and IL-18 plasma levels. In brief, we reveal the importance of platelets in HIV-1 infection, which might secrete more cytokines and mediate CD8+ T-cell phenotypic characteristics by forming platelet–CD8+ T-cell aggregates, which are related to poor prognosis. [ABSTRACT FROM AUTHOR]

Blood is one of the human tissues in which potassium bromate (KBrO3) is hazardous. This investigation aims to assess the impact of Corchorus olitorius (C. olitorius) on KBrO3-induced haematological parameters derangement. C. olitorius leaves were extracted with a soxhlet extractor and a solvent of 95% ethanol. Groups A, B, C, and D were created from twenty-four mature male Wistar rats acclimated for seven days. Group A was given distilled water orally. In addition to the 100 mg/kg b.w of KBrO3 given to groups B, C, and D of animals, 100 and 200 mg/kg body weight of C. olitorius were also administered to groups C and D respectively. After the 28-day treatment period, blood samples were collected for examination. Animals intoxicated with KBrO3 demonstrated substantial (P<0.05) decrease in most blood parameters compared to the animals in the control group (haemoglobin level, red blood cell count, packed cell volume, total white cell count, neutrophil count, lymphocyte count, monocyte count and platelet count). The disordered haematological parameters were, however, dose-dependently corrected in the potassium bromate-intoxicated rats treated with C. olitorius. KBrO3 caused a significant decrease in haemoglobin level, red blood cell count, packed cell volume, total white blood cell count, neutrophil count, lymphocyte count, monocyte count and platelet count as well as elevated erythrocyte sedimentation rate (ESR), but C. olitorius treatment reversed these effects. Therefore, more studies are needed to further validate these findings. [ABSTRACT FROM AUTHOR]

Background: Inflammation is integral to diabetes pathogenesis. The novel hematological inflammatory biomarker, platelet to white blood cell ratio (PWR), is linked with various conditions such as chronic kidney disease and stroke. However, the association of this novel clinical indicator with diabetes still remains unclear, which is investigated in this study. Materials and Methods: A total of 10,973 Chinese participants were included and grouped according to the tertiles of PWR (T1, T2, and T3 groups). Diagnosis of prediabetes and diabetes adhered to American Diabetes Association criteria. Binary logistic regression was adopted to assess the relationship between PWR and both diabetes and prediabetes. The dose-response relationship of PWR and diabetes was examined using restricted cubic spline regression. Subgroup and interaction analyses were conducted to investigate potential covariate interactions. Results: Individuals with higher PWR had better lifestyles and lipid profiles (all P < 0.05). After adjusting for all the covariates, the T2 group had a 0.83-fold (95% CI: 0.73-0.93, P < 0.01) risk of diabetes and that for the T3 group was 0.68-fold (95% CI: 0.60-0.78. P < 0.001). Dose-response analysis identified non-linear PWR-diabetes associations in the general population and females (both P < 0.05), but absent in males. Participants with prediabetes in the T2 and T3 groups had lower risks of diabetes (OR = 0.80 for the T2 group, P < 0.001 and 0.68 for the T3 group, P<0.001) in the full models. All the sensitivity analysis support consistent conclusions. Conclusions: An increase in PWR significantly correlates with reduced diabetes risks. A non-linear PWR-diabetes relationship exists in the general population and females, but not in males. The correlation between PWR and diabetes indicates that PWR holds potentials in early identification and prevention of diabetes. [ABSTRACT FROM AUTHOR]

Abstract Depression is a common psychiatric disorder among patients undergoing maintenance haemodialysis (MHD). Depression may reportedly contribute to poor prognosis in several ways, including its effects on platelet function. We hypothesised that depression contributes to the occurrence of cardiocerebral vascular events (CCVE) and dysfunction of arteriovenous fistula (DAVF) in patients undergoing MHD through its effects on platelets. In this prospective cohort study, patients undergoing MHD were recruited and divided into depression and non-depression groups according to their Hamilton Depression Scale (HAMD) scores. The 286 enrolled patients had 103 occurrences of depressive symptoms (prevalence = 36.01%). Compared with the non-depression group, depression group had a significantly higher cumulative prevalence of CCVE and DAVF during follow-up. Cox regression analysis indicated that higher HAMD scores and lower plasma platelet distribution width (PDW) were common risk factors for CCVE and DAVF. Furthermore, HAMD scores were significantly negatively correlated with plasma PDW and was the main variable affecting changes in PDW, as indicated by multiple linear regression analysis. Depression may increase the risk of CCVE and DAVF in patients undergoing MHD by activating platelets. Plasma PDW may be a convenient indicator of platelet activation status and may predict the risk of CCVE and DAVF.

Objective To analyze the structure of CD36, search the possible B cell epitopes and prepare multi-antigen peptides(MAP) with B cell epitopes, so as to provide a preliminary experimental basis for the preparation of CD36 antibodies using MAP with B cell epitopes. Methods The potential B cell epitopes of CD36 were analyzed by bioinformatics methods, including physical and chemical properties, secondary structure, potential phosphorylation and glycosylation sites. Eight-branch MAP with CD36 B cell epitopes were synthesized by FMOC using polylysine as the core matrix. The purity of MAPs was analyzed by reverse high-performance liquid chromatography chromatography(RP-HPLC), and the molecular weight of MAPs was determined by mass spectrometry. Results CD36 is a stable and hydrophilic alkaline protein, with multiple phosphorylation and glycosylation sites and strong antigenicity, and its secondary structure is mainly characterized by irregular curls. Four potential B cell epitopes were obtained and 4 MAPs containing potential B cell epitopes were prepared. RP-HPLC analysis showed that the purity of the MAPs were above 85%, and the molecular weight of 3 MAPs was consistent with the expected theoretical molecular weight. Conclusion CD36 on platelet has strong antigenicity. MAPs containing CD36 B cell epitopes can provide the experimental basis for the preparation and related research of CD36 antibodies.

Abstract Objective Several pathological conditions trigger the formation of microvesicles (MVs), including infectious diseases such as COVID-19. The shedding of MVs increases the levels of inflammatory factors (e.g., interleukin-6; IL-6) and ultimately leads to an inflammatory cascade response, while also increasing the procoagulant response. The current study aimed to evaluate the level of circulating MVs and their procoagulant activity as well as the serum level of IL-6 in patients with COVID-19 and healthy controls. In this case-control study, 65 patients with COVID-19 and 30 healthy individuals were sampled after obtaining written informed consent. MVs counting was measured using conjugated CD61, CD45, CD235a, and Annexin-V antibodies. Additionally, the procoagulant activity of MVs and the IL-6 level were estimated using enzyme-linked immunosorbent assay (ELISA). Results The majority of MVs were platelet-derived MVs (PMVs). Patients with COVID-19 had significantly higher levels of MVs, procoagulant MVs, and IL-6 compared to healthy controls (p

Tumor metastasis, the apex of cancer progression, poses a formidable challenge in therapeutic endeavors. Circulating tumor cells (CTCs), resilient entities originating from primary tumors or their metastases, significantly contribute to this process by demonstrating remarkable adaptability. They survive shear stress, resist anoikis, evade immune surveillance, and thwart chemotherapy. This comprehensive review aims to elucidate the intricate landscape of CTC formation, metastatic mechanisms, and the myriad factors influencing their behavior. Integral signaling pathways, such as integrin-related signaling, cellular autophagy, epithelial-mesenchymal transition, and interactions with platelets, are examined in detail. Furthermore, we explore the realm of precision nanomedicine design, with a specific emphasis on the anoikis‒platelet interface. This innovative approach strategically targets CTC survival mechanisms, offering promising avenues for combatting metastatic cancer with unprecedented precision and efficacy. The review underscores the indispensable role of the rational design of platelet-based nanomedicine in the pursuit of restraining CTC-driven metastasis.

Objective To study the effect of Salidroside(Sal) on platelet activation and aggregation and the interaction between human platelets and MDA-MB-468 cells of breast cancer. Methods Human platelets were collected, platelet suspension was prepared, and platelets were treated with different concentrations of Sal. The effects of Sal on platelet activation and aggregation were detected by thromboelastogram(TEG) and flow cytometry. Breast cancer MDA-MB-468 cells were cultured in vitro, and human platelets were treated with different concentrations of Sal, and then activated by thrombin. The effects of Sal on the interaction between platelets and MDA-MB-468 cells were analyzed by adhesion test and scratch test. Results TEG detection: The ADP inhibition rate in the blank control group was (10.97±12.69)%, and the ADP inhibition rate in all Sal intervention groups was higher than that in the blank control group (P

Abstract Immune thrombocytopenia (ITP) is the most common acquired primary hemostatic disorder in dogs. Immune thrombocytopenia less commonly affects cats but is an important cause of mortality and treatment‐associated morbidity in both species. Immune thrombocytopenia remains a diagnosis of exclusion for which diagnostic guidelines are lacking. Primary, or non‐associative, ITP refers to autoimmune platelet destruction. Secondary, or associative, ITP arises in response to an underlying disease trigger. However, evidence for which comorbidities serve as ITP triggers has not been systematically evaluated. To identify key diagnostic steps for ITP and important comorbidities associated with secondary ITP, we developed 12 Population Evaluation/Exposure Comparison Outcome (PECO) format questions. These questions were addressed by evidence evaluators utilizing a literature pool of 287 articles identified by the panelists using a structured search strategy. Evidence evaluators, using panel‐designed templates and data extraction tools, summarized evidence and created guideline recommendations that then were integrated by diagnosis and comorbidity domain chairs. The revised PECO responses underwent a Delphi survey process to reach consensus on final guidelines. A combination of panel expertise and PECO responses were employed to develop algorithms for diagnosis of ITP in dogs and cats, which also underwent 4 iterations of Delphi review. Comorbidity evidence evaluators employed an integrated measure of evidence (IME) tool to determine evidence quality for each comorbidity; IME values combined with evidence summaries for each comorbidity were integrated to develop ITP screening recommendations, which also were subjected to Delphi review. Commentary was solicited from multiple relevant professional organizations before finalizing the consensus. The final consensus statement provides clinical guidelines for the diagnosis of, and underlying disease screening for, ITP in dogs and cats. The systematic consensus process identified numerous knowledge gaps that should guide future studies. This statement is a companion manuscript to the ACVIM Consensus Statement on the Treatment of Immune Thrombocytopenia.

Abstract Management of immune thrombocytopenia (ITP) in dogs and cats is evolving, but there are no evidence‐based guidelines to assist clinicians with treatment decisions. Likewise, the overall goals for treatment of ITP have not been established. Immunosuppressive doses of glucocorticoids are the first line treatment, but optimal treatment regimens beyond glucocorticoids remain uncertain. Additional options include secondary immunosuppressive drugs such as azathioprine, modified cyclosporine, and mycophenolate mofetil, usually selected based on clinician preference. Vincristine, human IV immunoglobulin (hIVIg), and transfusion of platelet or red blood cell–containing products are often used in more severe cases. Splenectomy and thrombopoietin receptor agonists are usually reserved for refractory cases, but when and in which patient these modalities should be employed is under debate. To develop evidence‐based guidelines for individualized treatment of ITP patients, we asked 20 Population Intervention Comparison Outcome (PICO) format questions. These were addressed by 17 evidence evaluators using a literature pool of 288 articles identified by a structured search strategy. Evidence evaluators, using panel‐designed templates and data extraction tools, summarized evidence and created guideline recommendations. These were integrated by treatment domain chairs and then refined by iterative Delphi survey review to reach consensus on the final guidelines. In addition, 19 non‐PICO questions covering scenarios in which evidence was lacking or of low quality were answered by expert opinion using iterative Delphi surveys with panelist integration and refinement. Commentary was solicited from multiple relevant professional organizations before finalizing the consensus. The rigorous consensus process identified few comparative treatment studies, highlighting many areas of ITP treatment requiring additional studies. This statement is a companion manuscript to the ACVIM Consensus Statement on the Diagnosis of Immune Thrombocytopenia in Dogs and Cats.

Abstract To evaluate the clinical significance of PLT, MPV, and PDW in monitoring malaria treatment efficacy and predicting disease progression. A total of 31 patients with imported malaria were selected as the observation group, while 31 non-malaria patients with fever were selected as controls. The observation group was subdivided into a complication group and a non-complication group according to the occurrence of complications during treatment. Additionally, on the 1st day (within 24 h), the 3rd day, and the 5th day following admission, a comprehensive blood routine examination, Plasmodium microscopic examination, and colloidal gold assay were conducted. The blood routine examination results were compared before and after treatment among patients in the observation group and the control group. Moreover, the study involved dynamic monitoring and analysis of the levels and variations in PLT, MPV, and PDW within both the complication group and the non-complication group. The Plasmodium density was negatively correlated with PLT before treatment. There were significant differences were observed in PLT, MPV, and PDW (P 0.05) within the observation group before and after treatment. The PLT, MPV, and PDW levels in the complication group and the non-complication group exhibited an upward trend after treatment. Further, the PLT of patients in the complication group was significantly lower than that in the non-complication group. Additionally, the PLT, MPV, and PDW levels in the complication group and the non-complication group increased gradually from the time of admission to the 3rd and 5th day of treatment. Notably, the PLT in the complication group was consistently lower than that in the non-complication group. The continuous monitoring of PLT, MPV, and PDW changes plays a crucial role in assessing malaria treatment efficacy and prognosis in these individuals.

Abstract Erectile dysfunction (ED) is related to nutritional and inflammatory factors. The hemoglobin, albumin, lymphocyte, and platelet score (HALP), a new index reflecting the nutritional and inflammatory status, has been associated with a higher risk of diabetic retinopathy, particularly at lower values (≤ 42.9). However, studies focusing on the relationship between HALP and ED risk are scarce. Hence, this study aimed to investigate the association between HALP and ED. Data were extracted from the National Health and Nutrition Examination Survey (NHANES) conducted between 2001 and 2004. Based on self-reported data, participants were classified into either the ED group or the non-ED group. Next, the HALP score was categorized into four quartiles (Q1–4). Weighted multivariate regression analysis was performed to assess the relationship between categorical HALP and ED risk. Additionally, restricted cubic spline (RCS) analysis was conducted to examine the association between continuous HALP scores and ED risk. Furthermore, subgroup analyses were conducted to examine the association between categorical HALP and the risk of ED based on age, as well as the status of hypertension, diabetes and cardiovascular disease. Finally, a mediation analysis was carried out to investigate the mediating effect of HALP and related parameters on the association between urinary cobalt levels and ED. Initially, the data of 21,161 participants were collected. After implementing the inclusion and exclusion criteria, 3406 participants were included in the final analyses. Weighted multivariate regression analysis demonstrated that the Q4 HALP group was associated with a lower risk of ED (OR 0.96, 95% confidence intervals 0.92–1.00, P = 0.037). Meanwhile, RCS analysis showed that HALP was nonlinearly associated with the risk of ED. In addition, subgroup analyses demonstrated that participants in the Q3/4 HALP group had a significantly lower ED risk than those in the Q1 group among patients aged ≥ 50 years, as well as those with hypertension and diabetes. Lastly, mediation analysis revealed that HALP and its associated parameters had a marginal average causal mediation effect on the relationship between urinary cobalt levels and ED risk (P > 0.05). In US adults, high HALP scores were correlated with a lower risk of ED. The relationship was more pronounced in participants aged ≥ 50 years with hypertension and diabetes. Furthermore, HALP and its parameters may not mediate the association between urinary cobalt levels and ED risk.

Abstract The platelet/high-density lipoprotein ratio (PHR) has been identified as a significant indicator of inflammation and a hypercoagulable state, demonstrating a strong link with the severity of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS). However, its correlation with hyperuricemia has not yet been documented. This study utilized a cross-sectional design, analyzing data collected from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2016 in the United States. The platelet/high-density lipoprotein ratio (PHR) was determined by dividing the number of platelets (PLT) by the level of high-density lipoprotein cholesterol (HDL-C). We employed multivariable logistic regression analyses, generalized additive models, and subgroup analyses to investigate the correlation between PHR and hyperuricemia. The study revealed a hyperuricemia prevalence of 18.56%. Analysis indicated a significant positive correlation between PHR and the risk of hyperuricemia (OR 1.11, 95% CI 1.08, 1.14). This correlation remained consistent across different subgroups including age, ethnicity, gender, and body mass index (BMI). Smooth curve fitting demonstrated a saturation effect between PHR and the risk of hyperuricemia. PHR is positively correlated with hyperuricemia and may serve as a novel biomarker for predicting the onset of this condition. Additionally, targeted interventions to improve PHR might help reduce the incidence of hyperuricemia.