Gut microbiota-derived bile acids are crucial in the pathogenesis and treatment of metabolic diseases. However, their impact on platelet activation and thrombosis in coronary artery disease (CAD) remains poorly understood. In this study, we observed reduced serum deoxycholic acid (DCA) in patients with CAD and an underrepresentation of Bacteroides vulgatus in the gut microbiota of patients with CAD, affecting DCA metabolism. We used Takeda G-protein-coupled receptor 5 (TGR5) inhibitors and TGR5 knockout mice to show that DCA inhibited agonist-induced platelet activation and thrombosis by interacting with the platelet TGR5. Oral gavage treatments with DCA, B. vulgatus and stool from healthy individuals suppressed platelet hyperreactivity and thrombosis in atherosclerotic ApoE-/- mice, reduced microvascular thrombosis and protected the heart from myocardial ischemia/reperfusion injury. Here we describe the role of the bile acid DCA in platelet activation and suggest that targeting the gut microbiota and/or altering bile acid metabolism may be beneficial to treat CAD-associated thrombosis.

The purpose of this study was to evaluate the association between four easy-to-measure inflammatory markers and the 90-day outcomes with acute ischemic stroke (AIS) patients who received intravenous thrombolytic therapy with recombinant tissue plasminogen activator (rt-PA). These included the neutrophil percentage-to-albumin ratio (NPAR), the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), and the combined NPAR+NLR index.

This study enrolled 151 AIS patients who were treated with rt-PA (0.9 mg/kg). Clinical data were collected and NPAR, NLR, PLR were calculated from the admission blood work. The patients were followed up for 90 days after stroke onset and subsequently categorized into two groups based on the modified Rankin Scale (mRS): a favorable outcome group (111 patients, mRS ≤ 2) and a poor outcome group (40 patients, mRS > 2).

In this study, we foud elevated level of albumin and lymphocyte counts are protective factors for short-term prognosis. Age, neutrophil percentage, NPAR, NLR, PLR, NIHSS score, and fasting blood glucose (FBG) are associated with poor short-term prognosis. Among these, age, NPAR, NLR, and NIHSS score are independent risk factors for poor short-term prognosis.

NPAR, NLR, PLR, and the combined NPAR+NLR index may have predictive value for poor short-term outcomes in AIS patients following thrombolysis. NPAR demonstrates the highest predictive capability, in the following order: NPAR > NPAR+NLR > NLR > PLR.

The systemic immune-inflammation index (SII) has been used effectively to effectively assess the prognosis of patients with a variety of diseases. But few evidence on the relationship between SII and long-term prognosis of myocardial infarction. We thus aimed to evaluate the relationships of cumulative exposure to SII and its accumulation time course with major adverse cardiovascular events (MACE) events in patients with acute myocardial infarction after percutaneous coronary intervention. To evaluate the predictive value of SII in MACE events in patients with acute myocardial infarction. A total of 480 patients with acute ST-elevation myocardial infarction who underwent emergency coronary angiography at the Department of Cardiology, Affiliated Hospital of Hebei University from August 2022 to August 2023 were enrolled in this study. Eighteen patients were lost to follow-up, with a loss rate of 3.8%. Time-weighted cumulative SII was calculated as the weighted sum of the mean SII value for each time interval, then normalized by total exposure duration, the exposure duration was from hospitalization to 1-year follow-up. Duration of high SII exposure was defined as the duration with high SII and ranged from hospitalization to 1-year follow-up. The time course of SII accumulation was categorized by the combination of time-weighted cumulative SII < or ≥ median and SII slope. At 1-year follow-up, after adjusting for potential confounders, the time-weighted cumulative SII was divided into 2 groups. The S2 group which is above the median had a higher risk of MACE (hazard ratio, 1.090; 95% confidence interval 1.035-1.149), the high time-weighted cumulative SII group with a positive slope had a higher risk of MACE (hazard ratio, 4.096; 95% confidence interval 1.851-9.065). Long-term cumulative exposure to SII increases the risk of MACE in patients with acute ST-elevation myocardial infarction undergoing coronary angiography, and late high SII results in a higher risk of MACE events at the same time-weighted cumulative SII, underscoring the importance of late inflammation control.

IntroductionPeripheral artery disease (PAD) poses a growing clinical challenge due to an aging population, despite advances in treatment methods. Various scoring systems have emerged to predict high-risk patients, including the HALP (hemoglobin, albumin, lymphocyte, and platelet) score, known for predicting prognosis in cancers and stroke. This study assesses the HALP score's relation to lesion severity and long-term mortality in PAD patients.MethodsWe retrospectively analyzed 305 symptomatic PAD patients undergoing endovascular intervention. The following formula was used to calculate the HALP score: hemoglobin (g/L) × albumin (g/L) × lymphocyte count (/L) / platelet count (/L). Lesion severity was classified by TASC-II: TASC AB and TASC CD. Mortality data were obtained from hospital and social security records.ResultsThe study involved 305 patients (mean age 64.4 ± 11.8 years; 72.1% male), divided into survivors (208) and non-survivors (97). ROC analysis identified HALP score as the strongest predictor of long-term mortality (AUC: 0.736; 95% CI: 0.679-0.793; p < .001). HALP score (HR, 0.087; 95% CI, 0.025-1.300; p < .001), age (p < .001), DM (p = .007), and CRP (p = .013) independently predicted mortality. Kaplan-Meier analysis showed higher HALP scores linked to lower long-term mortality (Log-rank: 20.102, p < .001), with an average follow-up of 48 ± 18 months.ConclusionThe HALP score emerged as a robust predictor of PAD prognosis, surpassing individual components and other parameters. Lower HALP scores correlated with more severe lesions and reduced life expectancy.

Fc receptor γ subunit (FcRγ) activation plays a crucial role in cancer carcinogenesis. Here, we aimed to uncover the impact of FcRγ on circulating tumor cells (CTC) colonization and the underlying mechanism. FcRγ deficient (FcRγ-/-) mice were used to investigate the functional effects of FcRγ in cancer metastasis, and the results demonstrated that FcRγ deficiency significantly promotes metastasis. The tumor metastasis effect, antiplatelet, platelet or neutrophil infusion experiments were conducted with FcRγ deficient (FcRγ-/-) mice and wild type mice (WT), bearing B16F10 or LCC tumor cells. Blood routine test, flow cytometry, immunofluorescent staining and in vivo image were applied for analysis. Platelet adhesion and neutrophil chemotaxis were analyzed by flow cytometry and ELISA in vitro. Platelet adoptive model was used for mimicing early colonization stage. Our results indicated FcRγ deficiency significantly promoted tumor metastasis accompanied with increased number of platelet and neutrophil in the lung. Further investigation showed that FcRγ-/- platelet infusion, rather than FcRγ-/- neutrophils, promoted CTC colonization. While platelet inhibitor Aspirin abrogated the platelet-mediated infiltration of neutrophil in the lung. Mechanistically, platelet FcRγ deficiency facilitated the adhesion of platelets and cancer cells and increased secretion of CXCL5 and CXCL7 which triggered the platelet-induced neutrophil recruitment. In sum, our study indicates that FcRγ is a restrainer in controlling cancer metastasis through regulating the adhesion of platelets and cancer cells and recruiting more neutrophils, which provides a potential target for anti-metastatic therapies. The level of FcRγ expression in platelets could act as a novel biomarker for cancer metastasis.

Stroke recurrence remains a critical challenge in clinical neurology, necessitating the identification of reliable predictive markers for better management and treatment strategies. This study investigates the interaction between lipoprotein-associated phospholipase A2 (Lp-PLA2) and platelets as a potential predictor for stroke recurrence, aiming to refine risk assessment and therapeutic approaches. In a retrospective cohort of 580 ischemic stroke patients, we analyzed clinical data with a focus on Lp-PLA2 and platelet levels. By using multivariable logistic regression, we identified independent predictors of stroke recurrence. These predictors were then used to develop a comprehensive nomogram. The study established diabetes mellitus, hypertension, low-density lipoprotein (LDL), Lp-PLA2 levels, and platelet counts as independent predictors of stroke recurrence. Crucially, the interaction parameter Lp-PLA2 * platelet (multiplication of Lp-PLA2 and platelet count) exhibited superior predictive power over each factor considered separately. Our nomogram incorporated diabetes mellitus, cerebral infarction causes, hypertension, LDL, and the Lp-PLA2 * platelet count interaction and demonstrated enhanced accuracy in predicting stroke recurrence compared to traditional risk models. The interaction between Lp-PLA2 and platelets emerged as a significant predictor for stroke recurrence when integrated with traditional risk factors. The developed nomogram offers a novel and practical tool in molecular neurobiology for assessing individual risks, facilitating personalized treatment strategies. This approach underscores the importance of multifactorial assessment in stroke management and opens avenues for targeted interventions to mitigate recurrence risks.

Different treatment approaches exist for non-ST elevation acute coronary syndrome (ACS) patients. This study assessed the systemic immune inflammatory response index (SIIRI) for its prognostic value and incremental clinical utility in determining optimal timing for percutaneous coronary intervention (PCI) in non-ST elevation myocardial infarction (NSTEMI) patients, particularly when troponin levels are initially negative.

This study included 1270 ACS patients: 437 STEMI, 422 NSTEMI, and 411 unstable angina. Patients were stratified by SIIRI levels measured at admission, and coronary artery disease severity was evaluated using the SYNTAX score. The primary endpoint was major adverse cardiovascular events (MACE), including cardiovascular death, non-fatal myocardial infarction, stroke, and revascularization. Secondary endpoints encompassed individual MACE components and heart failure hospitalisations.

The mean age was 54.93 years (83% male). SIIRI levels were significantly higher in STEMI patients (6.83 ± 6.43 × 10 5 ) compared to NSTEMI (4.5 ± 5.39 × 10 5 ) and unstable angina (3.48 ± 2.83 × 10 5 ) ( P  < 0.001). Area under the curve for SIIRI distinguished NSTEMI and unstable angina from STEMI (0.81 and 0.80), with optimal cut-off points of 4.80 × 10 5 and 4.25 × 10 5 . In NSTEMI, 24.6% presented within 2 h of symptom onset, were troponin-negative, yet had elevated SIIRI. Post-PCI, SIIRI > 4.93 × 10 5 correlated with increased MACE at 1 year (17.2% vs 5%).

NSTEMI and unstable angina patients with SIIRI values >4.80 × 10 5 and 4.25 × 10 5 respectively, may require urgent intervention (<2 h). SIIRI can be of significant utility in patients of NSTEMI who present earlier with negative troponins. SIIRI can also aid in identifying high-risk individuals post-PCI, providing a valuable tool for early and accurate assessment.

Early neurological deterioration (END) and recurrence of vessel blockage frequently complicate intravenous thrombolysis (IVT) for acute ischemic stroke (AIS). Several studies have indicated the potential effectiveness of the early initiation (within < 24 h) of antiplatelet therapy (APT) after IVT. However, conflicting results have been reported by other studies. We aimed to offer a thorough overview of the current literature through a systematic review and meta-analysis.

Our systematic review and meta-analysis were prospectively registered on PROSPERO (ID: CRD42023488173) following the PRISMA guidelines. We systematically searched Web of Science, SCOPUS, PubMed, and Cochrane Library until May 5, 2024. Rayyan. ai facilitated the screening process. The R statistical programming language was used to calculate the odds ratios and conduct a meta-analysis. Our primary outcomes were excellent functional recovery (modified Rankin Scale score 0-1), symptomatic intracranial hemorrhage (sICH), and mortality.

Eight studies involving 2,134 participants were included in the meta-analysis. Early APT showed statistically significant increased odds of excellent functional recovery (mRS 0-1) compared to the standard APT group (OR, 1.81; [95% CI: 1.10, 2.98], p = 0.02). However, we found no differences between the early and standard APT groups regarding sICH (OR, 1.74; [95% CI: 0.91, 3.33], p = 0.10) and mortality (OR, 0.88; [95% CI: 0.62, 1.24]; p = 0.47).

Early APT within 24 h of IVT in stroke patients is safe, with no increase in bleeding risk, and has a positive effect on excellent functional recovery. However, there was a statistically insignificant trend of increased sICH with early APT, and the current evidence is based on highly heterogeneous studies. Further large-scale RCTs are warranted.

Glioblastoma (GBM) is one of the most aggressive cancers due to its high mortality rate in spite of intensive treatment. It may be happened because of drug resistance against their typical receptors, since these receptor genes are often mutated by environmental stress. So identifying mutated oncodriver genes which could be used as potential drug target is essential in order to develop effective new therapeutic drugs as well as better prognosis for GBM patients. In this study, we analyzed whole exome sequencing (WES) profiles of NCBI database on GBM and matched-normal (control) samples originated from astrocyte like neural stem cells (NSC) of subventricular zone (SVZ) to explore GBM-causing mutated oncodriver genes, since SVZ is considered as the origin of GBM development. We detected 16 mutated oncodriver genes. Then, filtering by differential co-expression analysis based on independent RNA-Seq profiles of CGGA database revealed 10 genes as dysregulated oncodriver genes. Following that, 3 significantly overexpressed oncodriver genes (MTCH2, VWF, and WDR89) were identified as potential drug targets. Then molecular mechanisms of GBM development were investigated by these three overexpressed driver genes through gene ontology (GO), KEGG-pathways, Gene regulatory network (GRN) and mutation analysis. Finally, overexpressed oncodriver genes guided top-ranked six drug agents (Irinotecan, Imatinib, etoposide, pazopanib, trametinib and cabozanitinib) were recommended against GBM through molecular docking study. Most of our findings received support by the literature review also. Therefore, the findings of this study might carry potential values to the wet-lab researchers for further investigation in terms of diagnosis and therapies of GBM.

The platelet-to-lymphocyte ratio (PLR) is a novel indicator of inflammation, but research on the links and mechanisms between the PLR and long-term health conditions is lacking. This study aimed to evaluate the relationship between phenotypic age (PhenoAge) mediated PLR and mortality among US adults.

A total of 37,182 participants from the National Health and Nutrition Examination Survey (NHANES) database (1999-2018) were included to evaluate the PLR's relevance to survival by Cox regression models. The associations between the PLR and mortality were apparent using restricted cubic spline regression. Mediation analyses were conducted to investigate the mediated effects of PhenoAge on the associations of PLR with mortality.

Compared to the PLR in Quintile 1 participants, the multivariable-adjusted Cox model showed the PLR in Quintile 5 was linked with greater risks of death from all-cause (HR, 1.14; 95 % CI: 1.04-1.25), cardiovascular disease (CVD) (HR, 1.26; 95 % CI: 1.01-1.57) and respiratory disease (HR, 1.98; 95 % CI: 1.35-2.90). The risk of death from cancer was approximately 28 % lower for participants with the PLR in the fourth quintile. Restricted cubic splines showed the U-shaped relationships between PLR and all-cause and cancer mortality, and the positively linear relationships between PLR and cardiovascular disease (CVD) and respiratory mortality. Moreover, mediation analysis revealed that PhenoAge partially mediated 45.33 %, 44.26 %, and 15.35 % of the associations of PLR with all-cause, CVD, and respiratory disease mortality, respectively.

The PLR, a valuable index that should be recommended for use, was independently linked with all-cause and cause-specific mortality, with PhenoAge playing a partial mediating role in the relationships.

Enzymatically oxygenated phospholipids (eoxPL) from lipoxygenases (LOX) or cyclooxygenase (COX) are prothrombotic. Their generation in arterial disease, and their modulation by cardiovascular therapies is unknown. Furthermore, the Lands cycle acyl-transferases that catalyze their formation are unidentified. eoxPL were measured in platelets and leukocytes from an atherosclerotic cardiovascular disease (ASCVD) cohort and retrieved human arterial thrombi from three anatomical sites. The impact of age, gender, and aspirin was characterized in platelets from healthy subjects administered low-dose aspirin. The role of lysophosphatidylcholine acyltransferase 3 (LPCAT3) in eoxPL biosynthesis was tested using an inhibitor and a cell-free assay. Platelets from ASCVD patients generated lower levels of COX-derived eoxPL but elevated 12-LOX-diacyl forms, than platelets from healthy controls. This associated with aspirin and was recapitulated in healthy subjects by aspirin supplementation. P2Y12 inhibition had no impact on eoxPL. LPCAT3 inhibition selectively prevented 12-LOX-derived diacyl-eoxPL generation. LPCAT3 activity was not directly altered by aspirin. P2Y12 inhibition or aspirin had little impact on eoxPL in leukocytes. Complex aspirin-dependent gender and seasonal effects on platelet eoxPL generation were seen in healthy subjects. Limb or coronary (ST-elevation myocardial infarction, STEMI) thrombi displayed a platelet eoxPL signature while carotid thrombi had a white cell profile. EoxPL are altered in ASCVD by a commonly used cardiovascular therapy, and LPCAT3 was identified as the acyltransferase generating aspirin-sensitive 12-LOX diacyl forms. These changes to the phospholipid composition of blood cells in humans at risk of thrombosis may be clinically significant where the procoagulant membrane plays a central role in driving elevated thrombotic risk.

Drugs blocking the renin-angiotensin-aldosterone system may offer benefit on endothelial function, inflammation, and hemostasis in addition to the effects of reducing blood pressure. We have shown antithrombin effects by treatment with the angiotensin converting enzyme (ACE) inhibitor ramipril. As thrombin is a key inducer of platelet aggregation, we hypothesized that treatment with ramipril could modulate platelet reactivity and endothelial glycocalyx (eGCX) function. This study assessed platelet activity (CD40 ligand and P-selectin) and eGCX markers (E-selectin, hyaluronan, syndecan-1, and thrombomodulin) in 59 individuals with mild-to-moderate hypertension, randomized double-blind to ramipril 10 mg or doxazosin 8 mg od for 12 weeks. Ramipril and doxazosin similarly reduced blood pressure. Antihypertensive treatment reduced CD40 ligand (p < .001) with no interaction (p = .405) by treatment group (reductions by ramipril and doxazosin were 8.7 ± 30.8 ng/L, p = .044, and 13.4 ± 25.5 ng/L, p = .002, respectively). There were no changes in P-selectin by treatment within (p = .556) or between (p = .256) treatment groups. No changes were observed in E-selectin, hyaluronan, syndecan-1, or thrombomodulin by antihypertensive treatment (p = .091-.991), or between ramipril and doxazosin (p = .223-.999). Our results show a potential reduction of platelet activity by ACE inhibitor treatment. Also, the alpha 1-adrenoceptor antagonist doxazosin may reduce platelet activation. Neither drug influenced eGCX markers.

Cardiovascular disease (CVD) is a major complication in peritoneal dialysis (PD) patients. Previous studies have demonstrated that platelet distribution width (PDW) is associated with cardiovascular events in hemodialysis (HD) patients. In this study, we hypothesized that elevated PDW can predict all-cause and cardiovascular mortality in PD patients.

We recruited PD patients for a single-center retrospective cohort study from 1 January 2007, to 30 June 2020. Receiver-operating characteristic (ROC) curves were made to determine the PDW cutoff value for predicting all-cause mortality. The propensity score matching (PSM) method was used to improve the equilibrium between groups. The relation of PDW with all-cause and cardiovascular mortality was analyzed by Cox proportional hazards models. Restricted cubic spline (RCS) models were used to determine whether there was a linear relationship between PDW and all-cause and cardiovascular mortality.

A total of 720 PD patients were screened, and 426 PD patients were enrolled after PSM. After adjusting for confounders, Cox proportional hazards models showed that the PDW value was positively correlated with the risk of all-cause and cardiovascular mortality (HR = 1.162, 95% CI 1.057-1.278, p = 0.002 and HR = 1.200, 95% CI 1.041-1.382, p = 0.012). The adjusted RCS analysis further showed that the relationship of PDW with all-cause and cardiovascular mortality was linear (p for nonlinearly = 0.143 and 0.062).

Elevated PDW is independently associated with all-cause and cardiovascular mortality in PD patients.

Backgrounds/Objectives: Abnormal platelet functions are associated with human morbidity and mortality. Platelets have emerged as critical regulators of numerous physiological and pathological processes beyond their established roles in hemostasis and thrombosis. Maintaining physiological platelet function is essential to hemostasis and preventing platelet-associated diseases such as cardiovascular disease, cancer metastasis, immune disorders, hypertension, diabetes, sickle cell disease, inflammatory bowel disease, sepsis, rheumatoid arthritis, myeloproliferative disease, and Alzheimer's disease. Platelets become hyperactive in obesity, diabetes, a sedentary lifestyle, hypertension, pollution, and smokers. Platelets, upon activation, can trawl leukocytes and progenitor cells to the vascular sites. Platelets release various proinflammatory, anti-inflammatory, and angiogenic factors and shed microparticles in the circulation, thus promoting pathological reactions. These platelet-released factors also maintain sustained activation, further impacting these disease processes. Although the mechanisms are unknown, multiple stimuli induce platelet hyperreactivity but involve the early pathways of platelet activation. The exact mechanisms of how hyperactive platelets contribute to these diseases are still unclear, and antiplatelet strategies are inevitable for preventing these diseases. Reducing platelet function during the early stages could significantly impact these diseases. However, while this is potentially a worthwhile intervention, using antiplatelet drugs to limit platelet function in apparently healthy individuals without cardiovascular disease is not recommended due to the increased risk of internal bleeding, resistance, and other side effects. The challenge for therapeutic intervention in these diseases is identifying factors that preferentially block specific targets involved in platelets' complex contribution to these diseases while leaving their hemostatic function at least partially intact. Since antiplatelet drugs such as aspirin are not recommended as primary preventives, it is essential to use alternative safe platelet inhibitors without side effects.

A systematic search of the PUBMED database from 2000 to 2023 was conducted using the selected keywords: "functional foods", "polyphenols", "fatty acids", "herbs", fruits and vegetables", "cardioprotective agents", "plant", "platelet aggregation", "platelet activation", "clinical and non-clinical trial", "randomized", and "controlled".

Potent natural antiplatelet factors have been described, including omega-3 fatty acids, polyphenols, and other phytochemicals. Antiplatelet bioactive compounds in food that can prevent platelet hyperactivity and thus may prevent several platelet-mediated diseases, including cardiovascular disease.

This narrative review describes the work during 2000-2023 in developing functional foods from natural sources with antiplatelet effects.

Thrombocytopenia is a common symptom and one of the warning signs of dengue virus (DENV) infection. Platelet depletion is critical as it may lead to other severe dengue symptoms. Understanding the molecular events of this condition during dengue infection is challenging because of the multifaceted factors involved in DENV infection and the dynamics of the disease progression. Platelet levels depend on the balance between platelet production and platelet consumption or clearance. Megakaryopoiesis and thrombopoiesis, two interdependent processes in platelet production, are hampered during dengue infection. Conversely, platelet elimination via platelet activation, apoptosis and clearance processes are elevated. Together, these anomalies contribute to thrombocytopenia in dengue patients. Targeting the molecular events of dengue-mediated thrombocytopenia shows great potential but still requires further investigation. Nonetheless, the application of new knowledge in this field, such as immature platelet fraction analysis, may facilitate physicians in monitoring the progression of the disease.

Toxicofera reptile venoms are composed of several toxins, including serine proteases. These proteases are glycosylated enzymes that affect the prey's hemostatic system. Their actions extend across the coagulation cascade, the kallikrein-kinin system, and platelet activation. Despite their specificity for different substrates, these enzymes are homologous across all toxicoferans and display high sequence similarity. The aim of this review is to compile decades of knowledge about venom serine proteases, showing the diversity of biochemically and biophysically characterized enzymes, their structural characteristics, advances in understanding their origin and evolution, as well as methods of obtaining enzymes and their biotechnological applications.

Severe acute pancreatitis (SAP) is characterized by inflammation, with inflammatory immune cells playing a pivotal role in disease progression. This study aims to understand variations in specific immune cell subtypes in SAP, uncover their mechanisms of action, and identify potential biological markers for predicting Acute Pancreatitis (AP) severity.

We collected peripheral blood from 7 untreated SAP patients and employed single-cell RNA sequencing for the first time to construct a transcriptome atlas of peripheral blood mononuclear cells (PBMCs) in SAP. Integrating SAP transcriptomic data with 6 healthy controls from the GEO database facilitated the analysis of immune cell roles in SAP. We obtained comprehensive transcriptomic datasets from AP samples in the GEO database and identified potential biomarkers associated with AP severity using the "Scissor" tool in single-cell transcriptomic data.

This study presents the inaugural construction of a peripheral blood single-cell atlas for SAP patients, identifying 20 cell subtypes. Notably, there was a significant decrease in effector T cell subsets and a noteworthy increase in monocytes compared to healthy controls. Moreover, we identified a novel monocyte subpopulation expressing high levels of PPBP and PF4 which was significantly elevated in SAP. The proportion of monocyte subpopulations with high CCL3 expression was also markedly increased compared to healthy controls, as verified by flow cytometry. Additionally, cell communication analysis revealed insights into immune and inflammation-related signaling pathways in SAP patient monocytes. Finally, our findings suggest that the subpopulation with high CCL3 expression, along with upregulated pro-inflammatory genes such as S100A12, IL1B, and CCL3, holds promise as biomarkers for predicting AP severity.

This study reveals monocytes' crucial role in SAP initiation and progression, characterized by distinct pro-inflammatory features intricately linked to AP severity. A monocyte subpopulation with elevated PPBP and CCL3 levels emerges as a potential biomarker and therapeutic target.

Clotting, leading to thrombosis, requires interactions of coagulation factors with the membrane aminophospholipids (aPLs) phosphatidylserine and phosphatidylethanolamine. Atherosclerotic cardiovascular disease (ASCVD) is associated with elevated thrombotic risk, which is not fully preventable using current therapies. Currently, the contribution of aPL to thrombotic risk in ASCVD is not known. Here, the aPL composition of circulating membranes in ASCVD of varying severity will be characterized along with the contribution of external facing aPL to plasma thrombin generation in patient samples.

Thrombin generation was measured using a purified factor assay on platelet, leukocyte, and extracellular vesicles (EVs) from patients with acute coronary syndrome (n=24), stable coronary artery disease (n=18), and positive risk factor (n=23) and compared with healthy controls (n=24). aPL composition of resting/activated platelet and leukocytes and EV membranes was determined using lipidomics.

External facing aPLs were detected on EVs, platelets, and leukocytes, elevating significantly following cell activation. Thrombin generation was higher on the surface of EVs from patients with acute coronary syndrome than healthy controls, along with increased circulating EV counts. Thrombin generation correlated significantly with externalized EV phosphatidylserine, plasma EV counts, and total EV membrane surface area. In contrast, aPL levels and thrombin generation from leukocytes and platelets were not impacted by disease, although circulating leukocyte counts were higher in patients.

The aPL membrane of EV supports an elevated level of thrombin generation in patient plasma in ASCVD. Leukocytes may also play a role although the platelet membrane did not seem to contribute. Targeting EV formation/clearance and developing strategies to prevent the aPL surface of EV interacting with coagulation factors represents a novel antithrombotic target in ASCVD.

As people age, their ability to resist injury and repair damage decreases significantly. Platelet-rich plasma (PRP) has demonstrated diverse therapeutic effects on tissue repair. However, the inconsistency of patient outcomes poses a challenge to the practical application of PRP in clinical practice. Furthermore, a comprehensive understanding of the specific impact of aging on PRP requires a systematic investigation. We derived PRP from 6 young volunteers and 6 elderly volunteers, respectively. Subsequently, 95% of high-abundance proteins were removed, followed by mass spectrometry analysis. Data are available via ProteomeXchange with the identifier PXD050061. We detected a total of 739 proteins and selected 311 proteins that showed significant differences, including 76 upregulated proteins in the young group and 235 upregulated proteins in the elderly group. Functional annotation and enrichment analysis unveiled upregulation of proteins associated with cell apoptosis, angiogenesis, and complement and coagulation cascades in the elderly. Conversely, IGF1 was found to be upregulated in the young group, potentially serving as the central source of enhanced cell proliferation ability. Our investigation not only provides insights into standardizing PRP preparation but also offers novel strategies for augmenting the functionality of aging cells or tissues.

Thrombosis is the pathological clot formation under abnormal hemodynamic conditions, which can result in vascular obstruction, causing ischemic strokes and myocardial infarction. Thrombus growth under moderate to low shear (<1000 s-1) relies on platelet activation and coagulation. Thrombosis at elevated high shear rates (>10,000 s-1) is predominantly driven by unactivated platelet binding and aggregating mediated by von Willebrand factor (VWF), while platelet activation and coagulation are secondary in supporting and reinforcing the thrombus. Given the molecular and cellular level information it can access, multiscale computational modeling informed by biology can provide new pathophysiological mechanisms that are otherwise not accessible experimentally, holding promise for novel first-principle-based therapeutics. In this review, we summarize the key aspects of platelet biorheology and mechanobiology, focusing on the molecular and cellular scale events and how they build up to thrombosis through platelet adhesion and aggregation in the presence or absence of platelet activation. In particular, we highlight recent advancements in multiscale modeling of platelet biorheology and mechanobiology and how they can lead to the better prediction and quantification of thrombus formation, exemplifying the exciting paradigm of digital medicine.

The detrimental effects of cigarette smoking on cardiovascular health, particularly atherosclerosis and thrombosis, are well established, and more detailed mechanisms continue to emerge. As the fundamental pathophysiology of the adverse effects of smoking, endothelial dysfunction, inflammation, and thrombosis are considered to be particularly important. Cigarette smoke induces endothelial dysfunction, leading to impaired vascular dilation and hemostasis regulation. Factors contributing to endothelial dysfunction include reduced bioavailability of nitric oxide, increased levels of superoxide anion, and endothelin release. Chronic inflammation of the vascular wall is a central pathogenesis of smoking-induced atherosclerosis. Smoking systemically elevates inflammatory markers and induces the expression of adhesion molecules and cytokines in various tissues. Pattern recognition receptors and damage-associated molecular patterns play crucial roles in the mechanism underlying smoking-induced inflammation. Smoking-induced DNA damage and activation of innate immunity, such as the NLRP3 inflammasome, cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, and Toll-like receptor 9, are shown to amplify inflammatory cytokine expression. Cigarette smoke-induced oxidative stress and inflammation influence platelet adhesion, aggregation, and coagulation via adhesion molecule upregulation. Furthermore, it affects the coagulation cascade and fibrinolysis balance, causing thrombus formation. Matrix metalloproteinases contribute to plaque vulnerability and atherothrombotic events. The impact of smoking on inflammatory cells and adhesion molecules further intensifies the risk of atherothrombosis. Collectively, exposure to cigarette smoke exerts profound effects on endothelial function, inflammation, and thrombosis, contributing to the development and progression of atherosclerosis and atherothrombotic cardiovascular diseases. Understanding these intricate mechanisms highlights the urgent need for smoking cessation to protect cardiovascular health. This comprehensive review investigates the multifaceted mechanisms through which smoking contributes to these life-threatening conditions.

The systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) have previously demonstrated predictive value in coronary artery disease (CAD). We developed on an expanded, novel systemic immune-inflammation response index (SIIRI), calculated as peripheral neutrophil × monocyte × platelet ÷ lymphocyte count. We assessed 240 patients with an acute coronary syndrome that subsequently underwent percutaneous coronary intervention. CAD severity was measured using the SYNTAX score. Laboratory measurements, including cell counts, were obtained on admission. On multivariate analysis, the SIIRI was an independent predictor of severe CAD with an adjusted odds ratio (OR) of 1.666 [1.376-2.017] per 105-unit increase. The SIIRI had the highest area under the receiver operator curve of .771 [.709-.833] compared to the SII, SIRI neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio, and platelet-lymphocyte ratio. The optimal cut-off for SIIRI was 4.3 × 105, with sensitivity = 69.9% and specificity = 75.8%. Increment in model performance resulting from adding SIIRI versus other inflammatory indices was assessed using discrimination, calibration, and goodness-of-fit measures. When added to a baseline model, the SIIRI resulted in a significant increase in the c-statistic and significant net reclassification index (.808, P < .0001) and integrated discrimination index (.129, P < .0001), and a decrease in Akaike and Bayesian information criteria.

In the field of critical care medicine, substantial research efforts have focused on identifying high-risk patient groups. This research has led to the development of diverse diagnostic tools, ranging from basic biomarkers to complex indexes and predictive algorithms that integrate multiple methods. Given the ever-evolving landscape of medicine, driven by rapid advancements, changing treatment strategies, and emerging diseases, the development and validation of diagnostic tools remains an ongoing and dynamic process. Specific changes in complete blood count components, such as neutrophils, lymphocytes, monocytes, and platelets, are key immune system responses influenced by various factors and crucial in systemic inflammation, injury, and stress. It has been reported that indices such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), and delta neutrophil index calculated using various ratios of these elements, are important predictors of various outcomes in conditions where the inflammatory process is at the forefront. In this narrative review, we concluded that NLR, PLR, SII, and SIRI show promise in predicting outcomes for different health conditions related to inflammation. While these tests are accessible, reliable, and cost-effective, their standalone predictive performance for a specific condition is limited.

Platelet Membrane Imitating Nanoparticles (PMINs) is a novel drug delivery system that imitates the structure and functionality of platelet membranes. PMINs imitate surface markers of platelets to target specific cells and transport therapeutic cargo. PMINs are engineered by incorporating the drug into the platelet membrane and encapsulating it in a nanoparticle scaffold. This allows PMINs to circulate in the bloodstream and bind to target cells with high specificity, reducing off-target effects and improving therapeutic efficacy. The engineering of PMINs entails several stages, including the separation and purification of platelet membranes, the integration of therapeutic cargo into the membrane, and the encapsulation of the membrane in a nanoparticle scaffold. In addition to being involved in a few pathological conditions including cancer, atherosclerosis, and rheumatoid arthritis, platelets are crucial to the body's physiological processes. This study includes the preparation and characterization of platelet membrane-like nanoparticles and focuses on their most recent advancements in targeted therapy for conditions, including cancer, immunological disorders, atherosclerosis, phototherapy, etc. PMINs are a potential drug delivery system that combines the advantages of platelet membranes with nanoparticles. The capacity to create PMMNs with particular therapeutic cargo and surface markers provides new possibilities for targeted medication administration and might completely change the way that medicine is practiced. Despite the need for more studies to optimize the engineering process and evaluate the effectiveness and safety of PMINs in clinical trials, this technology has a lot of potential.

Single-cell RNA sequencing studies have revealed transcriptional heterogeneity within the megakaryocytic lineage and the identified unique subsets. In this review, we discuss the functional and phenotypic plasticity of these subpopulations as well as the impacts on health and disease.

Megakaryocytes (MKs) can be transcriptionally categorized into platelet generating, niche supporting, immune, and cycling cells, which are distinguished by their unique gene expression patterns and cellular markers. Additionally, a significant population of these cells has been established to reside in the nonhematopoietic tissues and they display enhanced immune-related characteristics. Combined with the location in which the megakaryocytes exist, these cells can play unique roles dictated by their current environment and biological needs, including responding to changes in pathogen exposure.

Advances in megakaryocyte research has elucidated the existence of multiple subpopulations of MKs that serve different functions. These subpopulations implicate a greater potential for MKs to be regulators of health and suggest new avenues for treatments and therapies in related diseases.

Acute cerebral infarction (ACI) includes atherosclerotic and cardiogenic ACI and involves a thrombotic state, requiring antithrombotic treatment. However, the thrombotic state in ACI cannot be evaluated using routine hemostatic examinations. Plasma soluble C-type lectin-like receptor 2 (sCLEC-2) and D-dimer levels were measured in patients with ACI. Plasma sCLEC-2 and D-dimer levels were significantly higher in patients with ACI than in those without it. The sCLEC-2 × D-dimer formula was significantly higher in patients with ACI than in those without it. A receiver operating characteristic curve showed a high sensitivity, area under the curve, and odds for diagnosing ACI in the sCLEC-2 × D-dimer formula. Although the sCLEC-2 and D-dimer levels were useful for the differential diagnosis between cardiogenic and atherosclerotic ACI, the sCLEC-2 × D-dimer formula was not useful. sCLEC2 and D-dimer levels are useful for the diagnosis of ACI and the sCLEC2 × D-dimer formula can enhance the diagnostic ability of ACI, and sCLEC2 and D-dimer levels may be useful for differentiating between atherosclerotic and cardioembolic ACI.

Recently, the systemic immune inflammatory response index (SIIRI), a novel and expanded inflammatory response marker, has been an independent predictor of lesion severity in patients with acute coronary syndrome (ACS). However, its predictive role in patients with initially diagnosed coronary artery disease (CAD) remains to be explored.

We evaluated 959 patients with CAD undergoing an initial coronary intervention. Each patient had laboratory measurements, including blood cell counts, taken after admission and before interventional treatment. The primary endpoint was major cardiovascular events (MACEs), defined as cardiovascular death, nonfatal myocardial infarction(MI), and nonfatal stroke. The secondary endpoints included MACEs and readmission for congestive heart failure(HF).

During a mean follow-up period of 33.3±9.9 months, 229 (23.9%) MACEs were recorded. ROC curve analysis displayed that the best cut-off value of SIIRI for predicting MACEs was 247.17*1018/L2. Kaplan-Meier survival curve analysis showed that the survival rate of the low SIIRI group was higher than that of the high SIIRI group (P<0.001). Compared with the low SIIRI group, the high SIIRI group had a significantly higher risk of MACEs (187 cases (39.53%) vs.42 patients (8.64%), P<0.001). Univariate and multivariate Cox regression analyses displayed that high SIIRI levels were independently associated with the occurrence of MACEs in patients with initially diagnosed CAD undergoing percutaneous coronary intervention (PCI) (adjusted hazard ratio [HR]: 3.808, 95% confidence interval [CI%]: 2.643-5.486, P<0.001). Adding SIIRI to conventional risk factor models improved the predictive value of MACEs.

Elevated SIIRI is associated with adverse cardiovascular prognosis in patients with initially diagnosed CAD. SIIRI can be a simple and practical index to identify high-risk patients with CAD after PCI.

Daboxin P, reported earlier from the venom of Daboia russellii, disturbs the blood coagulation cascade by targeting factor X and factor Xa. The present study exhibits that Daboxin P also inhibits platelet aggregation induced by various agonists. The thrombin-induced platelet aggregation was inhibited maximum whereas inhibition of collagen-induced platelet aggregation was found to be 50% and no inhibition of adenosine diphosphate (ADP) and arachidonic acid-induced aggregation was observed. Daboxin P dose-dependently inhibited the thrombin-induced platelet aggregation with Anti-Aggregation 50 (AD50 ) dose of 55.166 nM and also reduced the thrombin-mediated calcium influx. In-silico interaction studies suggested that Daboxin P binds to thrombin and blocks its interaction with its receptor on the platelet surface. Quenching of thrombin's emission spectrum by Daboxin P and electrophoretic profiles of pull-down assay further reveals the binding between Daboxin P and thrombin. Thus, the present study demonstrates that Daboxin P inhibits thrombin-induced platelet aggregation by binding to thrombin.

Nitric oxide (NO) is a gaseous molecule that has a central role in signaling pathways involved in numerous physiological processes (e.g., vasodilation, neurotransmission, inflammation, apoptosis, and tumor growth). Due to its gaseous form, NO has a short half-life, and its physiology role is concentration dependent, often restricting its function to a target site. Providing NO from an external source is beneficial in promoting cellular functions and treatment of different pathological conditions. Hence, the multifaceted role of NO in physiology and pathology has garnered massive interest in developing strategies to deliver exogenous NO for the treatment of various regenerative and biomedical complexities. NO-releasing platforms or donors capable of delivering NO in a controlled and sustained manner to target tissues or organs have advanced in the past few decades. This review article discusses in detail the generation of NO via the enzymatic functions of NO synthase as well as from NO donors and the multiple biological and pathological processes that NO modulates. The methods for incorporating of NO donors into diverse biomaterials including physical, chemical, or supramolecular techniques are summarized. Then, these NO-releasing platforms are highlighted in terms of advancing treatment strategies for various medical problems.

Ischemic heart disease is one of the leading causes of death in the world, of which ST-segment elevation myocardial infarction (STEMI) is an important type. Inappropriate activation and accumulation of platelets typically induced thrombosis, which may result in acute vessel occlusion and STEMI. Multiple cytokines have been shown to regulate platelet activation, but the relationship between HMGB2 and platelet activation has not been elucidated.

We collected peripheral blood of STEMI patients and healthy adults, and mass spectrometry analysis of platelet proteins was conducted. The "edgeR" package was used to identify the differentially expressed proteins (DEPs). The Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene ontology (GO) and Gene Set Enrichment Analysis (GSEA) were used to identify the significantly changed pathways. Western blot and ELISA were used to detect the expression of a high mobility group box 2 (HMGB2). Flow cytometric analysis and platelet aggregation rate were performed to evaluate the activation of platelets.

We identified ALOX5, HIST1H1B, S100A11, HMGB2, and RPS15A were the top five up-regulated proteins by differential expression analysis. Western blot verified that the relative protein expression of HMGB2 in platelet was significantly higher in STEMI patients compared with control adults, and the results of ELISA indicated that the serum HMGB2 level increased and significantly correlated with neutrophil count in STEMI patients. Further investigation showed that the platelet aggregation induced by ADP, the activation of integrin αIIbβ3 and CD62P expression on platelet surface were all enhanced by the recombinant HMGB2 (rHMGB2).

In conclusion, HMGB2 may be the key molecule to regulate platelet activation in patients with STEMI, which may serve as a potential therapeutic target for STEMI.

To evaluate the efficacy and safety of short-term high-dose of dual antiplatelet therapy after 0.6 mg/kg rt-PA intravenous thrombolysis for acute ischemic stroke (AIS).

All 208 patients with AIS were randomized into group 1 (103 cases, after 0.6 mg/kg rt-PA, 300 mg of oral aspirin(ASP) q.d. and 225 mg of oral clopidogrel (CLO) q.d. for for 5 days, then 100 mg of oral ASP q.d. for the next 85 days and 75 mg of oral CLO q.d. for the next 16 days) and group 2 (105 cases, after 0.9 mg/kg rt-PA, 100 mg of oral ASP q.d. for 90 days and 75 mg of oral CLO q.d. for 21 days).The efficacy index was the mRS score, NIHSS score and recurrence risk of stroke, while the safety index was the incidence of bleeding events and mortality. All parameters were evaluated at 30 and 90 days after thrombolysis. Patients whose characteristics may provide the best treatment benefit were further analyzed using the logistic regression model in group 1.

The proportion of mRS scores between 0 and 1 in group 1 was higher than that in group 2 at both 30 days (44.7% vs 32.4%, P < .05) and 90 days (50.5% vs 35.2%, P < .05). Compared to group 2, the proportion of NIHSS scores less than 4 was significantly higher in group 1 at both 30 days (37.9% vs 25.7%, P < .05) and 90 days (46.6% vs 30.5%, P < .05). At 90 days, Group 1 had a lower stroke recurrence risk than Group 2 (3.9% vs 10.5%, P < .05). The incidence of SICH was significantly different between the 2 groups at both 30 days (2.9% vs 9.5%, P < .05) and 90 days (2.9% vs 10.5%, P < .05). However, other bleeding events and mortality rates were not significantly different between the 2 groups. The lower the baseline NIHSS score and the shorter the OTT, the more favorable the outcomes obtained at 90 days.

Compared to standard doses, short term high-dose dual antiplatelet therapy after 0.6 mg/kg rt-PA intravenous thrombolysis may be a good choice for AIS patients.

Fruits, vegetables, and other food items contain phytochemicals or secondary metabolites which may be considered non-essential nutrients but have medicinal importance. These dietary phytochemicals exhibit chemopreventive and therapeutic effects against numerous diseases. Polyphenols are secondary metabolites found in vegetables, fruits, and grains. These compounds exhibit several health benefits such as immune modulators, vasodilators, and antioxidants. This review focuses on recent studies on using dietary polyphenols to treat cardiovascular disorders, atherosclerosis, and vascular endothelium deficits. We focus on exploring the safety of highly effective polyphenols to ensure their maximum impact on cardiac abnormalities and discuss recent epidemiological evidence and intervention trials related to these properties. Kaempferol, quercetin, and resveratrol prevent oxidative stress by regulating proteins that induce oxidation in heart tissues. In addition, polyphenols modulate the tone of the endothelium of vessels by releasing nitric oxide (NO) and reducing low-density lipoprotein (LDL) oxidation to prevent atherosclerosis. In cardiomyocytes, polyphenols suppress the expression of inflammatory markers and inhibit the production of inflammation markers to exert an anti-inflammatory response. Consequently, heart diseases such as strokes, hypertension, heart failure, and ischemic heart disease could be prevented by dietary polyphenols.

Platelet-derived extracellular vesicles (PEVs) are a subset of EVs that are released from platelets, which are small nuclear cell fragments that play a critical role in hemostasis and thrombosis. PEVs have been shown to have important roles in a variety of physiological and pathological processes, including inflammation, angiogenesis, and cancer. Recently, researchers, including our group have utilized PEVs as drug delivery platforms as PEVs could target inflammatory sites both passively and actively. This review summarizes the biological function of PEVs, introduces recent applications of PEVs in targeted drug delivery, and provides an outlook for the further development of utilizing PEVs for drug delivery.

Blood platelets are central elements of the blood clotting response after wounding. Upon vessel damage, they bind to the surrounding matrix and contract the forming thrombus, thus helping to restore normal blood circulation. The hemostatic function of platelets is directly connected to their mechanics and cytoskeletal organization. The reorganization of the platelet cytoskeleton during spreading occurs within minutes and leads to the formation of contractile actomyosin bundles, but it is not known if there is a direct correlation between the emerging actin structures and the force field that is exerted to the environment. In this study, we combine fluorescence imaging of the actin structures with simultaneous traction force measurements in a time-resolved manner. In addition, we image the final states with superresolution microscopy. We find that both the force fields and the cell shapes have clear geometrical patterns defined by stress fibers. Force generation is localized in a few hotspots, which appear early during spreading, and, in the mature state, anchor stress fibers in focal adhesions. Moreover, we show that, for a gel stiffness in the physiological range, force generation is a very robust mechanism and we observe no systematic dependence on the amount of added thrombin in solution or fibrinogen coverage on the substrate, suggesting that force generation after platelet activation is a threshold phenomenon that ensures reliable thrombus contraction in diverse environments.

Anesthetic technique and postoperative pain management are crucial for total joint arthroplasty (TJA) patients. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and C-reactive protein (CRP) are new, simple, and cost-effective predictors for prognosis. The predictive value of NLR as an inflammatory marker can predict post-operative pain caused by inflammatory pathways secondary to surgical trauma. CRP is also the most sensitive and specific biomarker of inflammation whereas PLR was also recently considered a possible marker for inflammation which may further contribute to pain and sequelae. Thus, anesthetists can make decisions about the amount, time, and type of analgesic to use based on preoperative values of these parameters to provide maximum postoperative pain control and facilitate early rehabilitation. Thus, the current study was conducted to determine the relationship between CRP, NLR, and PLR levels and the intensity of pain in patients following total hip arthroplasty (THA) and total knee arthroplasty (TKA).

A total of 105 patients scheduled for THA and TKA fulfilling the study's inclusion criteria were enrolled. Inclusion criteria of the study were all the patients giving written consent, ASA Grade I-III, patients between 18 and 90 years who were scheduled for elective lower extremity TJA, and all the patients who remained admitted until stitches were removed. Patients were given intrathecal 15 mg hyperbaric bupivacaine via 25G atraumatic spinal needle in the L3-L4 interspace. The recorded data were demographic characteristics, preexisting comorbidities, number of blood transfusions, and operation time, postoperative analgesics given, duration of hospital stay, time of mobility, pain scoring as per visual analog scale (VAS) scoring system with an aim to establish a relationship between pre- and post-operative (Days 3 & 5) CRP, NLR, and PLR with post-operative pain after THA and TKA.

The present study demonstrated a significant correlation (p < 0.002) between preoperative and postoperative NLR with pain after TJA whereas PLR and CRP did not show any significant relationship with post-operative pain after THA and TKA. A significantly higher NLR ratio was observed for patients on all the periods of observation (pre-op., Day 3, and Day 5). Pre-op. and Day 5 NLR of patients who required transfusion were significantly higher than those who did not require transfusion and patients with higher NLR values could be mobilized significantly later and had significantly higher duration of hospital stay. The correlation of CRP levels and PLR levels at different time intervals did not show a significant correlation with Day 3 and Day 5 pain scores.

The present study demonstrated a significant correlation between preoperative and postoperative NLR with pain after TJA.

Edible mushrooms are popular functional foods attributed to their rich nutritional bioactive constituent profile influencing cardiovascular function. Edible mushrooms are omnipresent in various prescribed Dietary Approaches to Stop Hypertension, Mediterranean diet, and fortified meal plans as they are rich in amino acids, dietary fiber, proteins, sterols, vitamins, and minerals. However, without an understanding of the influence of mushroom bioactive constituents, mechanism of action on heart and allergenicity, it is difficult to fully comprehend the role of mushrooms as dietary interventions in alleviating hypertension and other cardiovascular malfunctions. To accomplish this endeavor, we chose to review edible mushrooms and their bioactive constituents in ameliorating hypertension. Hypertension and cardiovascular diseases are interrelated and if the former is managed by dietary changes, it is postulated that overall heart health could also be improved. With a concise note on different edible varieties of mushrooms, a particular focus is presented on the antihypertensive potential of mushroom bioactive constituents, mode of action, absorption kinetics and bioavailability. Ergosterol, lovastatin, cordycepin, tocopherols, chitosan, ergothioneine, γ-aminobutyric acid, quercetin, and eritadenine are described as essential bioactives with hypotensive effects. Finally, safety concerns on allergens and limitations of consuming edible mushrooms with special reference to chemical toxins and their postulated metabolites are highlighted. It is opined that the present review will redirect toxicologists to further investigate mushroom bioactives and allergens, thereby influencing dietary interventions for heart health.

Coronavirus disease 2019 (COVID-19) has spread, with thrombotic complications being increasingly frequently reported. Although thrombosis is frequently complicated in septic patients, there are some differences in the thrombosis noted with COVID-19 and that noted with bacterial infections. The incidence (6-26%) of thrombosis varied among reports in patients with COVID-19; the incidences of venous thromboembolism and acute arterial thrombosis were 4.8-21.0% and 0.7-3.7%, respectively. Although disseminated intravascular coagulation (DIC) is frequently associated with bacterial infections, a few cases of DIC have been reported in association with COVID-19. Fibrin-related markers, such as D-dimer levels, are extremely high in bacterial infections, whereas soluble C-type lectin-like receptor 2 (sCLEC-2) levels are high in COVID-19, suggesting that hypercoagulable and hyperfibrinolytic states are predominant in bacterial infections, whereas hypercoagulable and hypofibrinolytic states with platelet activation are predominant in COVID-19. Marked platelet activation, hypercoagulability and hypofibrinolytic states may cause thrombosis in patients with COVID-19.

Acute Coronary Syndrome (ACS) is a term that describes pathologies related to myocardial ischemia, and is comprised of unstable angina, non-ST elevation myocardial infarction, and ST elevation myocardial infarction. Urgent management of ACS is typically necessary to prevent future morbidity and mortality. Current medical recommendations of ACS management involve use of dual antiplatelet therapy, typically with aspirin and clopidogrel. However, newer therapies are being designed and researched to improve outcomes for patients with ACS. Vorapaxar is a novel antiplatelet therapy that inhibits thrombin-mediated platelet aggregation to prevent recurrence of ischemic events. It has been Food and Drug Administration approved for reduction of thrombotic cardiovascular events in patients with a history of MI or peripheral arterial disease with concomitant use of clopidogrel and/or aspirin, based upon the findings of the TRA 2°P-TIMI 50 trial. However, Vorapaxar was also found to have a significantly increased risk of bleeding, which must be considered when administering this drug. Based upon further subgroup analysis of both the TRA 2°P-TIMI 50 trial and TRACER trial, Vorapaxar was found to be potentially beneficial in patients with peripheral artery disease, coronary artery bypass grafting, and ischemic stroke. There are current trials in progress that are further evaluating the use of Vorapaxar in those conditions, and future research and trials are necessary to fully determine the utility of this drug.

Resistance exercise induces thrombocytosis and increases platelet activation and function. These changes might be related to exercise variables including exercise intensity and type.

We compared the effects of traditional resistance exercise (TRE) and circuit resistance exercise (CRE) on cellular markers of platelet activation and function.

In this crossover study ten healthy male (mean±SD: age, 25.6±2.4 years) subjects performed TRE encompassed 3 sets of 10 repetitions at 100% of 10-RM (10 repetition maximum) for 6 exercises, and CRE protocols included 3 sets of 10 repetitions at 100% of 10-RM for all 6 exercises consecutively, in two separate weeks. To measure platelet indices, PAC1, CD41a, CD42b and CD62P three blood samples were taken before, immediately after exercise, and after 30 min recovery.

Lactate concentration, blood pressure, platelet count (PLT), and mean platelet volume (MPV) were significantly (p <  0.05) increased following both resistance exercise trials. Significant increases in PAC1, and CD62P; and significant reductions for CD42b and CD41a were detected following both REs (p <  0.05). However, changes in PAC1 and CD62P were significantly different between the two protocols (p <  0.05), with higher increases detected following CRE.

Acute RE increases platelet indices and platelet activation; and that CRE results in higher platelet activation than TRE, probably due to exercise-induced increases in shear stress.