BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) and venous thromboembolism (VTE) are thought to share many common risk factors. Our study aimed to determine the frequencies of 5 thrombosis-related gene single nucleotide polymorphisms (SNPs) associated with VTE in patients with CTEPH (n 129) compared with a control group of healthy individuals without a history of VTE (n 2637).
METHODS: The SNPs of the following genes were investigated: F5 (F V Leiden, rs6025), F2 prothrombin (rs1799963), fibrinogen gamma (FGG, rs2066865), F11 (rs2289252) and ABO (non-O, rs8176719) in both groups.
RESULTS: The study found that the rs1799963 variant was more common in patients with chronic thromboembolic pulmonary hypertension (CTEPH) compared to the control group (p < .0001). The GA heterozygous variant showed a significant increase with an odds ratio (OR) of 4.480 (95% CI: 2.344-8.562) or a finding by maximum likelihood analysis (MLA) with p < .0001. Additionally, there was a notable increase in the rs8176719 variant with p < .0001 in CTEPH patients. Both the homozygous G/G variant and the heterozygous -/G variant also showed an increase, with OR of 4.2317 (95% CI: 2.45571-7.2919) and 2.4324 (95% CI: 1.46435-4.0403) respectively, or MLA (p < .0001 and p .0006). The study also revealed a higher prevalence of the heterozygous C/T variant of rs2289252 in CTEPH patients, with an OR of 1.5543 (95% CI: 1.02503-2.3568) or MLA (p .0379).
CONCLUSIONS: The study suggests that the observed gene polymorphisms F2 (rs1799963), ABO (rs8176719), and F11 (rs2289252) may play a role as independent heritable risk factors in the development of CTEPH.

OBJECTIVE: To investigate the clinical phenotypes and genotypes of children with congenital fibrinogen disorder (CFD).
METHODS: A retrospective analysis was conducted on the clinical data of 16 children with CFD. Polymerase chain reaction was used to amplify all exons and flanking sequences of the FGA, FGB, and FGG genes, and sequencing was performed to analyze mutation characteristics.
RESULTS: Among the 16 children, there were 9 boys (56%) and 7 girls (44%), with a median age of 4 years at the time of attending the hospital. Among these children, 9 (56%) attended the hospital due to bleeding events, and 7 (44%) were diagnosed based on preoperative examination. The children with bleeding events had a significantly lower fibrinogen activity than those without bleeding events (P<0.05). Genetic testing was conducted on 12 children and revealed a total of 12 mutations, among which there were 4 novel mutations, i.e., c.80T>C and c.1368delC in the FGA gene and c.1007T>A and C.1053C>A in the FGG gene. There were 2 cases of congenital afibrinogenemia caused by null mutations of the FGA gene, with relatively severe bleeding symptoms. There were 7 cases of congenital dysfibrinogenemia mainly caused by heterozygous missense mutations of the FGG and FGA genes, and their clinical phenotypes ranged from asymptomatic phenotype to varying degrees of bleeding.
CONCLUSIONS: The clinical phenotypes of children with CFD are heterogeneous, and the severity of bleeding is associated with the level of fibrinogen activity, but there is a weak association between clinical phenotype and genotype.
目的: 分析先天性纤维蛋白原病（congenital fibrinogen disorder, CFD）患儿临床表型和基因型的特征。方法: 回顾性分析16例CFD患儿的临床资料。聚合酶链反应技术扩增FGA、FGB、FGG基因全部外显子及侧翼序列并进行测序，分析变异特征。结果: 16例患儿，男9例（56%），女7例（44%），中位就诊年龄4岁。9例（56%）患儿因出血事件就诊，7例（44%）因术前检查发现。出血事件患儿的纤维蛋白原活性水平低于无出血事件患儿（P<0.05）。12例患儿完成基因检测，共检出12种变异，其中有4个新位点变异，分别为FGA基因c.80T>C和c.1368delC、FGG基因c.1007T>A和c.1053C>A。2例遗传性无纤维蛋白原血症均为FGA基因无效变异引起，有较重的出血症状。7例遗传性异常纤维蛋白原血症主要由FGG和FGA基因杂合错义变异引起，临床表型从无症状至不同程度出血。结论: CFD患儿临床表现具有异质性，患儿出血的严重程度与纤维蛋白原活性水平有关，但临床表型与基因型之间的相关性较弱。.

Epididymis plays a vital role in promoting sperm maturation and maintaining sperm viability. It has been shown the presence of nonviable sperm in cauda epididymis. We previously identified a secretory protein (260/280KDa oligomers) of hamster cauda epididymal principal cells that binds to nonviable sperm. The 260/280KDa oligomers are composed of 64kDa FGL2 (fibrinogen-like protein-2) and 33kDa FGL1) (fibrinogen-like protein-1). In addition, we have demonstrated that FGL2 is a phospholipid-activated serine protease; the conversion of prothrombin to thrombin by FGL2 followed by the conversion of soluble fibrinogen to insoluble fibrin polymers by thrombin. In the present study, we have shown the presence of a 56kDa fibrinogen β in hamster cauda sperm. The potential role of fibrinogen in hamster physiology is being discussed.

BACKGROUND: Activation of brown adipose tissue (BAT) has gained attention due to its ability to dissipate energy and counteract cardiometabolic diseases (CMDs).
METHODS: This study investigated the consequences of cold exposure on the BAT and liver proteomes of an established CMD mouse model based on LDL receptor-deficient (LdlrKO) mice fed a high-fat, high-sucrose, high-cholesterol diet for 16 weeks. We analyzed energy metabolism in vivo and performed untargeted proteomics on BAT and liver of LdlrKO mice maintained at 22 °C or 5 °C for 7 days.
RESULTS: We identified several dysregulated pathways, miRNAs, and transcription factors in BAT and liver of cold-exposed Ldlrko mice that have not been previously described in this context. Networks of regulatory interactions based on shared downstream targets and analysis of ligand-receptor pairs identified fibrinogen alpha chain (FGA) and fibronectin 1 (FN1) as potential crosstalk factors between BAT and liver in response to cold exposure. Importantly, genetic variations in the genes encoding FGA and FN1 have been associated with cardiometabolic-related phenotypes and traits in humans.
CONCLUSIONS: This study describes the key factors, pathways, and regulatory networks involved in the crosstalk between BAT and the liver in a cold-exposed CMD mouse model. These findings may provide a basis for future studies aimed at testing whether molecular mediators, as well as regulatory and signaling mechanisms involved in tissue adaption upon cold exposure, could represent a target in cardiometabolic disorders.

<b>Introduction:</b> Previous studies indicate a significant role of the inflammatory response in the etiopathogenesis of peripheral artery disease (PAD) and chronic pain (CP).<b>Aim:</b> The aim of the study was to determine the relationship between the concentration of SP and the level/concentration of inflammatory mediators (pro-inflammatory cytokines, positive and negative acute phase protein, anti-inflammatory cytokines) and pain intensity in people suffering from chronic pain (CP) in the course of PAD.<b>Material and methods:</b> We examined 187 patients of the Department of Vascular Surgery. As many as 92 patients with PAD and CP (study group) were compared to 95 patients with PAD without CP (control group). The relationship between SP and the level/concentration of fibrinogen, C-reactive protein (CRP), antithrombin III (AT), serum albumin, interleukin 10 (IL-10), tumor necrosis factor alpha (TNF-α) and pain intensity (Numeric Rating Scale; NRS) was analyzed. Statistical analysis was performed using the R program, assuming the level of statistical significance of α = 0.05.<b>Results:</b> Patients with CP had significantly higher levels of fibrinogen (P < 0.001), CRP (P < 0.001), SP (P < 0.001), IL-10 (P < 0.001), and lower serum albumin levels (P < 0.023). Higher SP concentration was associated with higher levels of IL-10, CRP, and pain intensity. In both groups, SP concentration correlated negatively with the level of fibrinogen (P < 0.001) as well as with albumin in the control group (P < 0.001).<b>Conclusions:</b> Thus, there is a relationship between the concentration of SP and fibrinogen, along with CRP, IL-10, and the intensity of pain in people suffering from CP in the course of PAD, and the level of albumin in the group without CP.

Liquid-infused polymers are recognized for their ability to repel foulants, making them promising for biomedical applications including catheter-associated urinary tract infections (CAUTIs). However, the impact of the quantity of free liquid layer covering the surface on protein and bacterial adhesion is not well understood. Here, we explore how the amount of free silicone liquid layer in infused silicone catheter materials influences the adhesion of bacteria and proteins relevant to CAUTIs. To alter the quantity of the free liquid layer, we either physically removed excess liquid from fully infused catheter materials or partially infused them. We then evaluated the impact on bacterial and host protein adhesion. Physical removal of the free liquid layer from the fully infused samples reduced the height of the liquid layer from 60 μm to below detection limits and silicone liquid loss into the environment by approximately 64% compared to controls, without significantly increasing the deposition of protein fibrinogen or the adhesion of the common uropathogen Enterococcus faecalis. Partially infused samples showed even greater reductions in liquid loss: samples infused to 70%-80% of their maximum capacity exhibited about an 85% decrease in liquid loss compared to fully infused controls. Notably, samples with more than 70% infusion did not show significant increases in fibrinogen or E. faecalis adhesion. These findings suggest that adjusting the levels of the free liquid layer in infused polymers can influence protein and bacterial adhesion on their surfaces. Moreover, removing the free liquid layer can effectively reduce liquid loss from these polymers while maintaining their functionality.

Rapid and accurate identification of cardiovascular diseases (CVDs) are crucial for timely medical interventions and improved patient outcomes. Fibrinogen (Fib) has emerged as a valuable biomarker for CVDs, playing a significant role in their early detection. Elevated levels of Fib are associated with an increased risk of developing CVD, highlighting its importance for more precise diagnosis and effective treatment strategies. In recent years, significant advancements have been made in developing biosensor-based approaches for detecting Fib, offering high sensitivity and specificity. This review aims to explore the impact of Fib on cardiovascular conditions, assess the current advancements, and discuss the future potential of biosensors in Fib research for diagnosing cardiovascular disorders. Furthermore, we evaluate various biosensor techniques, including optical, electrochemical, electronic, and gravimetric methods, in terms of their utility for measuring Fib in clinical samples such as serum, plasma, whole blood, and other body fluids. A comparative analysis of these techniques is conducted based on their performance characteristics. By providing a comprehensive overview of the relationship between Fib and cardiovascular ailments, this review aims to clarify the advancements in biosensor technology for Fib detection. The comparison of different biosensor techniques will aid researchers and clinicians in selecting the most suitable approach for their specific diagnostic needs. Ultimately, integrating biosensors into clinical practice has the potential to revolutionize the detection and management of CVDs, leading to improved patient care and outcomes.

Cerebrovascular alterations and innate immune activation are key features of Alzheimer\'s disease (AD). However, the mechanisms that link blood-brain barrier disruption to neurodegeneration are poorly understood and well-defined druggable targets at the neurovascular interface are limited. We identified the blood coagulation factor fibrinogen as necessary and sufficient for the induction of pathogenic neuroinflammation in neurologic diseases1. Fibrinogen induces spine elimination and promotes cognitive deficits in AD mouse models mediated by oxidative stress induction in microglia2, 3. Volume imaging in cleared mouse and human AD brains combined with repetitive in vivo two-photon imaging showed focal fibrinogen deposits associated with loss of dendritic spines independent of amyloid plaques. We developed a first-in-class fibrin-targeting immunotherapy to selectively inhibit fibrin-induced inflammation without interfering with its beneficial coagulation effects4. Fibrin-targeting immunotherapy entered the CNS, bound to fibrin, and inhibited amyloid-driven neurotoxicity and neurotoxic inflammatory gene programs in AD mice. Thus, fibrinogen links cerebrovascular damage with immune-mediated neurodegeneration and fibrin therapeutics may have important therapeutic implications inhibiting vascular-driven neurodegeneration in AD and related conditions. 1. Petersen et al., Nat Rev Neurosci. 2018, 19:283-301 2. Merlini et al. Neuron 2019, 101:1099-1108 3. Mendiola et al. Nat Immunol 2020, 21:513-524 4. Ryu et al. Nat Immunol 2018, 19:1212-1223.

One of the complications after total hip arthroplasty (THA) or total knee arthroplasty (TKA) is periprosthetic joint infection (PJI). Numerous studies have been performed to explore the value of biological parameters in the early identification of infection rates after THA and TKA. This study investigates alterations in inflammatory markers associated with PJI. This retrospective study focused on a cohort of patients with hip and knee arthroplasty treated between 2016 and 2022. CRP, ESR, and fibrinogen were observed preoperatively, on days one, three, six, and twenty-one postoperatively. From a total of 4076 THA and TKA performed during this period, 62 patients were identified with periprosthetic infections. We also identified the pathogens responsible for infections in order to assess if asymptomatic preoperative infections were involved in PJI. In patients with acute infections following TKA, days one and three postoperative recorded a CRP value below the expected range. The value of CRP in patients with early infection after THA was significantly increased on day six postoperative. ESR and fibrinogen values were not statistically significantly correlated with early PJI. The CRP level in acute PJI shows different patterns than those shown in the literature.

UNASSIGNED: Hemorrhagic transformation (HT) is a serious complication that can occur spontaneously after an acute ischemic stroke (AIS) or after a thrombolytic/mechanical thrombectomy. Our study aims to explore the potential correlations between fibrinogen levels and the occurrence of spontaneous HT (sHT) and HT after mechanical thrombectomy (tHT).
UNASSIGNED: A total of 423 consecutive AIS patients diagnosed HT who did not undergone thrombolysis and 423 age- and sex-matched patients without HT (non-HT) were enrolled. Fibrinogen levels were measured within 24 h of admission after stroke. The cohorts were trisected according to fibrinogen levels. The HT were further categorized into hemorrhagic infarction (HI) or parenchymal hematoma (PH) based on their imaging characteristics.
UNASSIGNED: In sHT cohort, fibrinogen levels were higher in HT patients than non-HT patients (p < 0.001 versus p = 0.002). High fibrinogen levels were associated with the severity of HT. HT patients without atrial fibrillation (AF) had higher levels of fibrinogen compared to non-HT (median 3.805 vs. 3.160, p < 0.001). This relationship did not differ among AF patients. In tHT cohort, fibrinogen levels were lower in HT patients than non-HT patients (p = 0.002). Lower fibrinogen levels were associated with the severity of HT (p = 0.004). The highest trisection of fibrinogen both in two cohorts were associated with HT [sHT cohort: OR = 2.515 (1.339-4.725), p = 0.016; that cohort: OR = 0.238 (0.108-0.523), p = 0.003].
UNASSIGNED: Our study suggests that lower fibrinogen level in sHT without AF and higher fibrinogen level in tHT are associated with more severe HT.