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BACKGROUND: Preeclampsia is a unique vascular disease during pregnancy that generally appears after 20 of weeks gestation or until 6 weeks after delivery. Left undiagnosed, preeclampsia can lead rapidly to death of both mother and fetus. OBJECTIVES: To verify the efficacy of peripheral blood inflammatory markers (BIMs)in diagnosing preeclampsia and compare them with results from other studies. METHODS: Our retrospective case-control study comprised two patient groups. Pregnant women with preeclampsia and pregnant women without preeclampsia were compared for BIMs: neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and mean platelet volume (MPV). The primary endpoint of our research was to assess the predictive power of BIMs for preeclampsia diagnosis. RESULTS: The sample size was calculated based on expected differences of BIMs between the control and study groups. Comparison of quantitative variables was conducted with independent sample t-test or alternatively by Wilcoxon rank sum test. The MPV values were slightly higher in the preeclampsia group, but not statistically significant. NLR and PLR did differentiate between study and control groups. CONCLUSIONS: The diagnostic accuracy of BIMs is unsatisfactory for preeclampsia diagnosis. Discrepancies concerning these values need to be clarified. Further large prospective studies are necessary to validate the potential factor accuracy in preeclampsia diagnosis.

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Antiplatelet and anticoagulant therapies are cornerstones of secondary prevention in high-risk cardiovascular patients. Whereas in former days the focus was set on effective antithrombotic effects, more recent trials and guidelines placed emphasis on a more balanced approach, thus including the bleeding risk for an individualized therapy. Type, strength, combination, and duration are important components to modify the individual bleeding risk. Novel antiplatelet and anticoagulant agents have shown promising results that might offer safer options in the future for high-risk cardiovascular patients. This review aims to give an overview about established drug target and pharmacologic approaches that are currently in the pipeline.

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Background: The chronic inflammatory immune response is a significant factor in the pathogenesis of benign gynecological diseases. The systemic immunoinflammatory index (SII) and the platelet-to-lymphocyte ratio (PLR) are commonly available biomarkers of inflammation. However, evidence of the relationship between SII and PLR in patients with adenomyosis is limited. This study aimed to investigate the relationship between SII and PLR in patients with adenomyosis. Methods: This cross-sectional study included 483 patients with adenomyosis who were first diagnosed at our institution between January 2019 and December 2021. Basic patient clinical information and inflammatory factors were collected for univariate analysis, smoothed curve fitting, and multivariate segmented linear regression. Results: The results of the univariate analysis showed a significant positive correlation between PLR levels and SII (P < 0.001). In addition, a nonlinear relationship between PLR and SII was tested using a smoothed curve fit after adjusting for potential confounders. Multiple segmented linear regression models showed a significant relationship between SII and PLR in both SII < 1,326.47 (ß 0.14, 95% CI: 0.12, 0.16; P < 0.0001) and >1,326.47 (ß 0.02, 95% CI: -0.01, 0.05; P = 0.2461). Conclusions: In conclusion, this study showed a nonlinear relationship between SII and PLR in patients with uterine adenomyosis. An increase in serum PLR levels correlates with an increase in SII before SII levels reach an inflection point.

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Immune-related adverse events (irAEs) impact outcomes, with most research focusing on early prediction (baseline data), rather than near-term prediction (one cycle before the occurrence of irAEs and the current cycle). We aimed to explore the near-term predictive value of neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), absolute eosinophil count (AEC) for severe irAEs induced by PD-1 inhibitors. Data were collected from tumor patients treated with PD-1 inhibitors. NLR, PLR, and AEC data were obtained from both the previous and the current cycles of irAEs occurrence. A predictive model was developed using elastic net logistic regression Cutoff values were determined using Youden's Index. The predicted results were compared with actual data using Bayesian survival analysis. A total of 138 patients were included, of whom 47 experienced grade 1-2 irAEs and 18 experienced grade 3-5 irAEs. The predictive model identified optimal α and λ through 10-fold cross-validation. The Shapiro-Wilk test, Kruskal-Wallis test and logistic regression showed that only current cycle data were meaningful. The NLR was statistically significant in predicting irAEs in the previous cycle. Both NLR and AEC were significant predictors of irAEs in the current cycle. The model achieved an area under the ROC curve (AUC) of 0.783, with a sensitivity of 77.8% and a specificity of 80.8%. A probability ≥ 0.1345 predicted severe irAEs. The model comprising NLR, AEC, and sex may predict the irAEs classification in the current cycle, offering a near-term predictive advantage over baseline models and potentially extending the duration of immunotherapy for patients.

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OBJECTIVE: To investigate the correlation between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and risk stratification indicators as well as thrombus burden in patients with moderate-to-high risk acute pulmonary embolism (APE), and to assess the changes in these parameters following interventional therapy. METHODS: This study retrospectively included patients with moderate-to-high risk APE who were admitted to the Department of Interventional Vascular Surgery at Putian First Hospital from May 2020 to May 2024. All patients received anticoagulation therapy, pulmonary artery catheter-directed thrombolysis, and/or mechanical thrombectomy. Patients were further divided into subgroup A if they did not present with any of the following conditions at admission: a) acute inflammatory diseases (including lung infections); b) malignant tumors; c) history of trauma or surgery within the past 2 months. Patients with any of the aforementioned conditions were classified as subgroup B. Additionally, 50 healthy individuals were randomly selected as the healthy control group. RESULTS: The NLR and PLR in subgroup A were significantly lower than those in subgroup B (P < .01). Compared with the healthy control group, the NLR in the APE group and subgroup A was significantly higher (P < .001). There were no significant differences in NLR and PLR between the troponin I-negative and troponin I-positive groups (P > .05), or between the N-terminal pro-B-type natriuretic peptide (NT-proBNP)-negative and NT-proBNP-positive groups (P > .05). There were no significant correlations between NLR and PLR with risk stratification indicators and pulmonary artery embolism index (P > .05). Compared with before treatment, NLR, troponin I, NT-proBNP, right ventricular diameter/left ventricular diameter ratio, and pulmonary artery embolism index were significantly reduced after treatment (P < .05), while there was no significant difference in PLR before and after treatment (P > .05). CONCLUSION: Elevated NLR in patients with APE, which decreases after effective treatment, may be used for assessing disease status and treatment efficacy. However, there is no correlation between NLR and risk stratification indicators or thrombus burden. PLR does not demonstrate significant value in assessing APE.

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Clinical manifestations of neonatal sepsis are often unspecified. Therefore, sepsis biomarkers could be used to support diagnosis while waiting for blood culture results, such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR). The aim of this study was to evaluate the role of NLR and PLR as diagnostic markers in neonatal sepsis. A cross-sectional study was conducted at Haji Adam Malik General Hospital, Medan, Indonesia, from April to October 2019. This study included neonates aged less than 28 days, diagnosed with suspected sepsis, and had no previous history of antibiotics administration. Patients underwent clinical assessment, laboratory examination, and blood culture. Patients were grouped into sepsis and non-sepsis based on the blood culture results. The median hematological examination and the range of NLR and PLR in both the sepsis and non-sepsis groups were subjected to analysis using the Mann-Whitney U test to assess differences. NLR and PLR optimal cut-off values were determined using a receiver operator curve (ROC) with a confidence interval of 95%. A total of 137 neonates were enrolled, of which 49 were classified as sepsis and 89 as non-sepsis based on blood culture results. The optimal cutoff values for NLR and PLR were 2.75 and 11.73. Using those cutoff values, NLR and PLR could predict neonatal sepsis with sensitivities of 52.1% and 47.9%, specificities of 50.6% and 47.2%, area under the curve (AUC) of 0.46 and 0.47, with p=0.525 and p=0.662, respectively. Further investigation is warranted to refine the NLR and PLR utility and enhance diagnostic accuracy in clinical practices.

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BACKGROUND: Numerous studies have demonstrated shared risk factors and pathophysiologic mechanisms between osteoporosis and cardiovascular disease. High-density lipoprotein cholesterol (HDL-C) and platelets have long been recognized as crucial factors for cardiovascular health. The platelet to HDL-C ratio (PHR) combines platelet count and high-density lipoprotein cholesterol (HDL-C) level, It is a novel biomarker for metabolic syndrome and cardiovascular disease. The platelet to HDL-C ratio (PHR) possibly reflects the balance between proinflammatory and anti-inflammatory states in the body. Therefore, we hypothesized that changes in PHR ratios may predict a predisposition to pro-inflammatory and increased bone resorption. However, the relationship between the platelet to HDL-C ratio (PHR) and bone mineral density (BMD) remains insufficiently understood. This study aimed to elucidate the relationship between the platelet to HDL-C ratio (PHR) index and bone mineral density (BMD). METHODS: Data from the NHANES 2005-2018 were analyzed, excluding adults with missing key variables and specific conditions. Nonlinear relationships were explored by fitting smoothed curves and generalized additive models, with threshold effects employed to calculate inflection points. Additionally, subgroup analyses and interaction tests were conducted. RESULTS: The study included 13,936 individuals with a mean age of 51.19 ± 16.65 years. Fitted smoothed curves and generalized additive models revealed a nonlinear, inverted U-shaped relationship between the two variables. Threshold effect analysis showed a significant negative association between PHR and total femur bone mineral density (BMD) beyond the inflection point of platelet to HDL-C ratio (PHR) 33.301. Subgroup analyses showed that a significant interaction between these two variables was observed only in the age and sex subgroups (P-interaction < 0.05). CONCLUSIONS: Our study identified a complex, nonlinear, inverted U-shaped relationship between platelet to HDL-C ratio (PHR) and total femur bone mineral density (BMD). These findings underscore the importance of maintaining optimal PHR levels to support bone health, especially in high-risk populations.

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Two monozygotic twins (Fitzpatrick skin type II 56-year-old women) with significant photoaging and mild to moderate global fine lines based on the modified Griffiths 10-point scale were enrolled in the study. The past medical etymology and laboratory evaluation were unremarkable. Each subject followed a standardized skin care regimen with topical platelet renewosomesTM (human platelet extract [HPE]) daily for a 12-week duration.1-4 In order to evaluate aesthetic outcomes/changes subjectively, three blinded board-certified plastic surgeons (Yael Halaas, K. Kay Durairaj, and Michael Somenek) compared photographs between baseline and 12-week follow-up (Figure 1). This evaluation was completed using the Global Aesthetic Improvement Scale (GAIS) and the modified Griffiths 10-point scale.5,6.

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OBJECTIVES: The associations between the neutrophil-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) with the responses of non-small cell lung cancer (NSCLC) patients receiving immune checkpoint inhibitors (ICI) and the NLR/PLR predictive potential were evaluated via meta-analysis. METHODS: A systematic review was conducted using the PubMed, Embase, and The Cochrane Library databases until October 2021. The relationship between NLR/PLR and overall survival (OS) and progression-free survival (PFS) was evaluated using pooled hazard ratios (HR). The relationship between NLR/PLR and overall response rate (ORR) and disease control rate (DCR) was assessed via pooled odds ratios (OR). Heterogeneity between studies, publication bias, subgroup and sensitivity analyses, trim and fill meta-analysis, and the contour-enhanced funnel plot were performed using the R software. RESULTS: A total of 44 (out of 875) studies met the eligibility criteria, providing a sample size of 4597 patients. Patients with a high NLR were statistically significantly associated with worse outcomes, including OS (pooled HR = 2.44; P < 0.001), PFS (pooled HR = 2.06; P < 0.001), DCR (pooled OR = 0.71; P < 0.001), and ORR (pooled OR = 0.33; P < 0.001). Similarly, a high PLR was associated with poorer outcomes in response to ICI drugs, including OS (pooled HR = 2.13; P < 0.001) and PFS (pooled HR = 1.61; P < 0.001). CONCLUSION: High NLR and PLR were associated with a statistically significant reduction in the efficacy of ICI drugs in NSCLC patients. Thereby, it is possible to use NLR and PLR as potential and available biomarkers in the clinical practice to predict the outcome of ICI treatment in NSCLC patients.

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BACKGROUND: Regenerative aesthetics has garnered significant attention. In this toolkit, exosomes are small extracellular vesicles derived from various sources such as platelets. OBJECTIVE: To characterize the cosmetic effect and tolerability of topical human platelet-derived extract (HPE), Intense Serum (Rion Aesthetics, Inc., Rochester, MN), on facial skin rejuvenation after 12 weeks of twice daily use without any confounding aesthetic procedures. MATERIALS AND METHODS: This prospective, single-arm, non-randomized, evaluator-blinded clinical study evaluated subjects at baseline and 12 weeks using participant questionnaires and photo-documentation with Canfield VISIA-CR 3D PRIMOS. The histological evaluation included Masson's Trichrome for collagen and Verhoeff-Van Gieson staining for elastin. Electron microscopy characterized collagen bundle thickness. RESULTS: Fifty-six participants (mean age: 54 years old) were enrolled. Following topical HPE use, 87.3% of subjects reported improvement in facial skin aging including sustained pigment reduction and improvement in luminosity and color evenness at 12 weeks (P≤0.001). Histology revealed a significant increase in collagen fibril thickness at 12 weeks (P≤0.0001). No serious adverse effects. CONCLUSION: This study demonstrates improvement in facial skin health after topical HPE use, supported by collagen and elastin formation in the dermis. The product is well-tolerated, and participants were satisfied with the overall cosmetic outcome. J Drugs Dermatol. 2024;23(9):735-740. doi:10.36849/JDD.8162.

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Background: Chronic obstructive pulmonary disease (COPD), usually caused by long-term tobacco smoking, is independently associated with systemic inflammation. However, little is known about the systemic inflammatory status of patients with early-stage COPD (classified as GOLD 1) and long-term smokers with normal lung function (LF). Here, we characterised the early changes in the associated inflammatory state in patients with GOLD 1 and in long-term smokers with normal LF. Methods: Fresh blood samples from 27 patients with GOLD 1, 27 long-term smokers and 14 non-smokers were analysed. Results: Ex vivo blood analysis revealed greater leucocyte-platelet adhesion to TNFα-stimulated pulmonary endothelium in patients with GOLD 1 than in smokers and non-smokers. In addition, platelet reactivity (platelet count and activation, and fibrinogen levels) and the frequency of leucocyte-platelet aggregates were higher in the GOLD 1 group than in the other groups. Some of these findings correlated with the severity of lung dysfunction, while platelet hyperactivity correlated positively with leucocyte-platelet adhesion. The GOLD 1 group also had a higher Th17/Treg ratio and higher circulating levels of IL-17C and C-reactive protein than the other groups. However, long-term smokers also had higher leucocyte counts and activation, and higher plasma levels of TNFα and IL-6 than non-smokers. Conclusion: Our data suggest that the altered inflammatory parameters in long-term smokers may represent early biomarkers of COPD. Accordingly, peripheral immune monitoring based on the above parameters may be useful to prevent disease progression in long-term smokers with normal LF and early COPD.

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BACKGROUND: Leukocyte- and platelet-rich fibrin (L-PRF) is an autologous platelet concentrate, prepared by centrifugation of blood and consisting of a dense fibrin network with incorporated leukocytes and platelets. This study aims to perform an in-depth analysis of the cells, growth factors, and transcriptome of L-PRF. METHODS AND RESULTS: Fresh, 1 week and 2 weeks cultured human L-PRF membranes and liquid L-PRF glue were characterized on cellular and transcriptional level using flow cytometry (n = 4), single-cell RNA sequencing (n = 5) and RT-qPCR. Growth factor kinetics were investigated using ELISA (EGF, VEGF, PDGF-AB, TGF-ß1, bFGF). L-PRF contained a large number of viable cells (fresh 97.14 ± 1.09%, 1 week cultured 93.57 ± 1.68%), mainly granulocytes in fresh samples (53.9 ± 19.86%) and T cells in cultured samples (84.7 ± 6.1%), confirmed with scRNA-seq. Monocytes differentiate to macrophages during 1 week incubation. Specifically arterial L-PRF membranes were found to release significant amounts of VEGF, EGF, PDGF-AB and TGF-ß1. CONCLUSION: We characterized L-PRF using in vitro experiments, to obtain an insight in the composition of the material including a possible mechanistic role for tissue healing. This was the first study characterizing L-PRF at a combined cellular, proteomic, and transcriptional level.

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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.

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The influence of chimeric antigen receptor T (CAR-T) cell therapy on platelet function in relapsed/refractory (R/R) multiple myeloma (MM) has not been thoroughly investigated. Our cohort comprised fifty MM patients treated with CAR-T cells. The mean platelet closure time (PCT) induced by collagen/adenosine diphosphate (CADP) in peripheral blood was significantly prolonged before lymphodepletion (195.24 ± 11.740 s) and notably reduced post-CAR-T cell therapy (128.02 ± 5.60 s), with a statistically significant improvement (67.22, 95% CI 46.91-87.53, P < 0.001). This post-treatment PCT was not significantly different from that of healthy controls (10.64, 95% CI 1.11-22.40, P > 0.05). Furthermore, a pronounced enhancement in PCT was observed in patients with a response greater than partial remission (PR) following CAR-T cell infusion compared to pre-treatment values (P < 0.001). An extended PCT was also associated with a less favorable remission status. In patients with cytokine release syndrome (CRS) grades 0-2, those with a PCT over 240.5 s exhibited a shorter progression-free survival (PFS), with median PFS times of 10.2 months for the PCT > 240.5 s group versus 22.0 months for the PCT ≤ 240.5 s group. Multivariate analysis revealed that a PCT value exceeding 240.5 s is an independent prognostic factor for overall survival (OS) in R/R MM patients after CAR-T cell therapy. The study demonstrates that CAR-T cell therapy enhances platelet function in R/R MM patients, and PCT emerges as a potential prognostic biomarker for the efficacy of CAR-T cell therapy.

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BACKGROUND: Recently, the effect of Lipoprotein(a) [Lp(a)] on thrombogenesis has aroused great interest, while inflammation has been reported to modify the Lp(a)-associated risks through an unidentified mechanism. PURPOSE: This study aimed to evaluate the association between platelet reactivity with Lp(a) and high-sensitivity C-reactive protein (hs-CRP) levels in percutaneous intervention (PCI) patients treated with clopidogrel. METHODS: Data were collected from 10,724 consecutive PCI patients throughout the year 2013 in Fuwai Hospital. High on-treatment platelet reactivity (HTPR) and low on-treatment platelet reactivity (LTPR) were defined as thrombelastography (TEG) maximum amplitude of adenosine diphosphate-induced platelet (MAADP) > 47 mm and < 31 mm, respectively. RESULTS: 6615 patients with TEG results were finally enrolled. The mean age was 58.24 ± 10.28 years and 5131 (77.6%) were male. Multivariable logistic regression showed that taking Lp(a) < 30 mg/dL and hs-CRP < 2 mg/L as the reference, isolated Lp(a) elevation [Lp(a) ≥ 30 mg/dL and hs-CRP < 2 mg/L] was not significantly associated with HTPR (P = 0.153) or LTPR (P = 0.312). However, the joint elevation of Lp(a) and hs-CRP [Lp(a) ≥ 30 mg/dL and hs-CRP ≥ 2 mg/L] exhibited enhanced association with both HTPR (OR:1.976, 95% CI 1.677-2.329) and LTPR (OR:0.533, 95% CI 0.454-0.627). CONCLUSIONS: The isolated elevation of Lp(a) level was not an independent indicator for platelet reactivity, yet the concomitant elevation of Lp(a) and hs-CRP levels was significantly associated with increased platelet reactivity. Whether intensified antiplatelet therapy or anti-inflammatory strategies could mitigate the risks in patients presenting combined Lp(a) and hs-CRP elevation requires future investigation.

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OBJECTIVE: In this study, we investigated 25-hydroxyvitamin D (25(OH)D, vitamin D), inflammatory hematologic ratios such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), monocyte/HDL-C ratio (MHR) and plasma atherogenic index (PAI) and possible relationships with insulin resistance (IR) in children. METHODS: A total of 210 individuals, including 96 children with IR and 114 children without IR, aged 6-18 years, who were admitted to the Pediatric Endocrinology Outpatient Clinic at Medicine Hospital, Istanbul Atlas University were included in our study. RESULT: Compared to patients without IR, NLR, PLR, SII, and MHR were significantly higher in patients with IR. Fasting insulin, PAI, homeostasis model assessment of insulin resistance (HOMA-IR), and HOMA-ß were significantly higher and quantitative insulin sensitivity check index (QUICKI) was considerably lower in patients with IR compared to those without IR. NLR, SII, and MHR were lower in normal vitamin D groups than the others (p < 0.001). PLR was lower in the group with normal vitamin D levels than the groups with insufficient or deficient levels of vitamin D (D < 21). CONCLUSIONS: We found that vitamin D deficiency in childhood is related to increased levels of circulating inflammatory markers (NLR, PLR, MHR, PAI), IR, and decreased insulin sensitivity. According to our results, supplementation of vitamin D may be beneficial in averting IR and enhanced systemic inflammation.

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OBJECTIVE: To investigate the effects of platelet-specific Rictor knockout on platelet activation and thrombus formation in mice. METHODS: PF4-Cre and Rictorfl/fl transgenic mice were crossed to obtain platelet-specific Rictor knockout (Rictor-KO) mice and wild-type mice (n=65), whose expression levels of Rictor, protein kinase B (AKT) and p-AKT were detected using Western blotting. Platelet counts of the mice were determined using routine blood tests, and hemostatic function was assessed by tail vein hemorrhage test. Venous thrombosis models were established in the mice to evaluate the effect of Rictor knockout on thrombosis. Platelet aggregation induced by ADP and thrombin was observed in Rictor-KO and wild-type mice, and flow cytometry was used to analyze the expression levels of integrin αIIbß3 and CD62P in resting and activated platelets. Plasma PF4 levels were determined with ELISA. Megakaryocytes from Rictor-KO and wild-type mice were incubated by vWF immunohistochemical antibody and APC-CD41 antibody to detect the number and ploidy of megakaryocytes, respectively. Platelet elongation on collagen surface was observed with scanning electron microscopy. RESULTS: Compared with the wild-type mice, Rictor-KO mice showed significantly decreased AKT phosphorylation, decreased platelet production, reduced thrombosis, and decreased platelet activation in response to ADP and thrombin stimulation. The Rictor-KO mice also showed lowered expression level of P-selectin protein and activation of integrin αIIbß3 with suppression of platelet extension, reduced plasma PF4 level and decreased number of megakaryocytes in the bone marrow. The ploidy of megakaryocytes and the mean area of proplatelets were both significantly decreased in Rictor-KO mice. CONCLUSION: Platelet-specific Rictor knockout inhibits platelet generation and activation to result in decreased thrombus formation in mice, suggesting the potential of mTORC2 activity inhibition as an efficient antithrombotic strategy.

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Thrombosis is a key process that determines acute coronary syndrome and ischemic stroke and is the leading cause of morbidity and mortality in the world, together with cancer. Platelet adhesion and subsequent activation and aggregation are critical processes that cause thrombus formation after endothelial damage. To date, high hopes are associated with compounds of natural origin, which show anticoagulant action without undesirable effects and can be proposed as supportive therapies. We investigated the effect of the new combination of four natural compounds, escin-bromelain-ginkgo biloba-sage miltiorrhiza (EBGS), on the initial process of the coagulation cascade, which is the adhesion of platelets to activated vascular endothelium. Our results demonstrated that EBGS pretreatment of endothelial cells reduces platelet adhesion even in the presence of the monocyte-lymphocyte population. Our data indicate that EBGS exerts its effects by inhibiting the transcription of adhesion molecules, including P-selectin, platelet membrane glycoprotein GP1b, integrins αV and ß3, and reducing the secretion of the pro-inflammatory cytokines interleukin 6, interleukin 8, and the metalloproteinases MMP-2 and MMP-9. Furthermore, we demonstrated that EBGS inhibited the expression of focal adhesion kinase (FAK), strictly involved in platelet adhesion, and whose activity is correlated with that of integrin ß3. The results shown in this manuscript suggest a possible inhibitory role of the new combination EBGS in the reduction in platelet adhesion to activated endothelium, thus possibly preventing coagulation cascade initiation.

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Platelet-rich plasma (PRP) has become an important regenerative therapy. However, the preparation method of PRP has not been standardized, and the optimal platelet concentration for PRP used in skin wound repair is unclear, leading to inconsistent clinical efficacy of PRP. Therefore, the development of standardized preparation methods for PRP and the investigation of the dose-response relationship between PRP with different platelet concentrations and tissue regeneration plays an important role in the development and clinical application of PRP technology. This study has developed an integrated blood collection device from blood drawing to centrifugation. Response surface methodology was employed to optimize the preparation conditions, ultimately achieving a platelet recovery rate as high as 95.74% for PRP (with optimal parameters: centrifugation force 1730× g, centrifugation time 10 min, and serum separation gel dosage 1.4 g). Both in vitro and in vivo experimental results indicate that PRP with a (2×) enrichment ratio is the most effective in promoting fibroblast proliferation and skin wound healing, with a cell proliferation rate of over 150% and a wound healing rate of 78% on day 7.

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