Platelet indices(PIs)including high mean platelet volume(MPV),plateletcrit(PLC),and platelet distribution width(PLDW)are associated with poor glycemic control.In addition,they can indicate prothrombotic and procoagula...Platelet indices(PIs)including high mean platelet volume(MPV),plateletcrit(PLC),and platelet distribution width(PLDW)are associated with poor glycemic control.In addition,they can indicate prothrombotic and procoagulation risk among patients with diabetes.PI measurement is cheap,quick and fits healthcare system needs in remote outreaching areas in low-income countries.However,a broader insight into their clinical implications in diabetes is lacking.To achieve a wider understanding,we reviewed PubMed/MEDLINE,Google Scholar and Cochrane Library for relevant articles investigating the role of PIs in diabetes mellitus.No limitation to the publication date was applied,which included all articles published up to August 17,2024.The terms used were MPV,PLC,PLDW,platelet large cell ratio,glycated hemoglobin(HbA1c),PIs,platelet activity and diabetes mellitus.Out of the 790 articles retrieved,187 full texts were reviewed,and 44 were included.PIs,when measurements are done promptly and within 2 h,could be short-term pointers to glycemic control in the life span of the platelets(2 wk).PIs are easy to perform,cheap and useful in remote outreaching areas with limited facilities where measurement of HbA1c is not available or cost-effective.However,PIs are not specific and are affected by demographic factors,such as pregnancy,renal failure,medications,hemoglobin and duration of diabetes.PIs could be implemented with daily blood glucose to inform doctors in low-income countries about their patients'glycemic control and cardiovascular risk.An important application might be when blood glucose control is needed quickly(before elective surgery).展开更多
Crimean-Congo hemorrhagic fever(CCHF)is a hemorrhagic fever caused by infection with the CCHF virus(CCHFV)and has a mortality rate of up to 30%.Thrombocytopenia is a hallmark of CCHF;however,the mechanisms underlying ...Crimean-Congo hemorrhagic fever(CCHF)is a hemorrhagic fever caused by infection with the CCHF virus(CCHFV)and has a mortality rate of up to 30%.Thrombocytopenia is a hallmark of CCHF;however,the mechanisms underlying this manifestation remain poorly understood.In addition to hemostasis,platelets play a crucial role in recognizing pathogens and mediating immune responses.We investigated the mechanisms underlying thrombocytopenia associated with CCHFV infection by analyzing the platelet transcriptome in mice.Interferon-induced transmembrane protein 3(IFITM3),a known antiviral factor,was significantly upregulated.The role of IFITM3 in response to CCHFV infection was characterized using the human megakaryoblast cell line MEG-01,considered a parental cell line of platelets.Although the CCHFV infection rate was limited,MEG-01 cells maintained the infection and replication of CCHFV,leading to increased IFITM3 protein expression.We demonstrated that IFITM3 overexpression efficiently inhibited CCHFV infection,whereas IFITM3 knockout promoted viral infection.An interaction between IFITM3 and the CCHFV glycoprotein Gc was identified,which suppressed CCHFV entry into cells.The IFITM3 CIL-TMD domain is critical for this interaction.These results suggest that IFITM3 is a restriction factor and plays an antiviral role during CCHFV infection.Elevated expression of IFITM3 in platelets indicates that this could be a common mechanism by which platelets protect against viruses,including CCHFV,which may reduce platelet consumption and destruction caused by CCHFV infection.These findings provide valuable insights into the pathogenesis of CCHF-associated thrombocytopenia and offer foundational theoretical support for future therapeutic strategies.展开更多
Platelets are small anucleate cells generated from megakaryocytes in the bone marrow. Although platelet genera- tion, maturation, and clearance are still not fully understood, significant progress has been made in the...Platelets are small anucleate cells generated from megakaryocytes in the bone marrow. Although platelet genera- tion, maturation, and clearance are still not fully understood, significant progress has been made in the last 1-2 dec- ades. In blood circulation, platelets can quickly adhere and aggregate at sites of vascular injury, forming the platelet plug （i.e. the first wave of hemostasis）. Activated platelets can also provide negatively charged phosphatidylserine- rich membrane surface that enhances cell-based thrombin generation, which facilitates blood coagulation （i.e. the second wave of hemostasis）. Platelets therefore play central roles in hemostasis. However, the same process of hemostasis may also cause thrombosis and vessel occlusion, which are the most common mechanisms leading to heart attack and stroke following ruptured atherosclerotic lesions. In this review, we will introduce the classical mechanisms and newly discovered pathways of platelets in hemostasis and thrombosis, including fibrinogen-inde- pendent platelet aggregation and thrombosis, and the plasma fibronectin-mediated ＂protein wave＂ of hemostasis that precedes the classical first wave of hemostasis. Furthermore, we briefly discuss the roles of platelets in inflam- marion and atherosclerosis and the potential strategies to control atherothrombosis.展开更多
AIM:To investigate the role of human platelets in liver fibrosis.METHODS:Severe combined immunodeficiency(SCID)mice were administered CCl4and either phosphate-buffered saline(PBS group)or human platelet transfusions(h...AIM:To investigate the role of human platelets in liver fibrosis.METHODS:Severe combined immunodeficiency(SCID)mice were administered CCl4and either phosphate-buffered saline(PBS group)or human platelet transfusions(hPLT group).Concentrations of hepatocyte growth factor(HGF),matrix metallopeptidases(MMP)-9,and transforming growth factor-β(TGF-β)in the liver tissue were compared between the PBS and the hPLT groups by enzyme-linked immunosorbent assay(ELISA)and Western blotting.The effects of a human platelet transfusion on liver fibrosis included the fibrotic area,hydroxyproline content,and-smooth muscle actin(α-SMA)expression,which were evaluated by picrosirius red staining,ELISA,and immunohistochemical staining using an anti-mouse-SMA antibody,respectively.Phosphorylations of mesenchymal-epithelial transition factor(Met)and SMAD3,downstream signals of HGF and TGF-β,were compared between the two groups by Western blotting and were quantified using densitometry.Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling.Furthermore,the accumulation of human platelets in the liver 2 h after platelet transfusion was compared between normal and fibrotic livers by immunohistochemical staining using an anti-human CD41 antibody.RESULTS:The fibrotic area and hydroxyproline content in the liver were both significantly lower in the hPLT group when compared to the PBS group(fibrotic area,1.7%±0.6%vs 2.5%±0.6%,P=0.03;hydroxyproline content,121±26 ng/g liver vs 156±47 ng/g liver,P=0.04).There was less α-smooth muscle actin staining in the hPLT group than in the PBS group(0.5%±0.1%vs 0.8%±0.3%,P=0.02).Hepatic expression levels of mouse HGF and MMP-9were significantly higher in the hPLT group than in the PBS group(HGF,109±13 ng/g liver vs 88±22 ng/g liver,P=0.03;MMP-9,113%±7%/GAPDH vs 92%±11%/GAPDH,P=0.04).In contrast,the concentration of mouse TGF-β in the liver tissue was significantly lower in the hPLT group than in the PBS group(22±5ng/g liver vs 39±6 ng/g liver,P=0.02).Phosphorylation of Met was more prevalent in the hPLT group than in the PBS group(37%±4%/GAPDH vs 20%±8%/GAPDH,P=0.03).Phosphorylation of SMAD3was weaker in the hPLT group than in the PBS group(60%±12%/GAPDH vs 84%±12%/GAPDH,P=0.1),although this difference was not significant.Furthermore,a lower rate of hepatocyte apoptosis was observed in the hPLT group than in the PBS group(5.9%±1.7%vs 2.9%±2.1%,P=0.02).Significant human platelet accumulation was observed in the fibrotic liver tissues,whereas few platelets accumulated in the normal liver.CONCLUSION:Human platelets inhibit liver fibrosis in SCID mice.Increased concentration of HGF in the liver suppresses hepatic stellate cell activation,induces MMPs,and inhibits hepatocyte apoptosis.展开更多
There is evidence that inflammatory bowel diseases (IBD) combine both inflammation and coagulation in their pathogenesis and clinical manifestations. Although platelets (PLT) are well known for their role in hemostasi...There is evidence that inflammatory bowel diseases (IBD) combine both inflammation and coagulation in their pathogenesis and clinical manifestations. Although platelets (PLT) are well known for their role in hemostasis, there are a rising number of studies supporting their considerable role as inflammatory amplifiers in chronic inflammatory conditions. IBD are associated with several alterations of PLT, including number, shape, and function, and these abnormalities are mainly attributed to the highly activated state of circulating PLT in IBD patients. When PLT activate, they increase in size, release a great variety of bio-active inflammatory and procoagulant molecules/particles, and express a variety of inflammatory receptors. These inflammatory products may represent a part of the missing link between coagulation and inflammation, and can be considered as possible IBD pathogenesis instigators. In clinical practice, thrombocytosis is associated both with disease activity and iron deficiency anemia. Controlling inflammation and iron replacement in anemic patients usually leads to a normalization of PLT count. The aim of this review is to update the role of PLT in IBD and present recent data revealing the possible therapeutic implications of anti-PLT agents in future IBD remedies.展开更多
AIM: To investigate the effect of mild steatotic liver on ischemia-reperfusion injury by focusing on Kupffer cells (KCs) and platelets. METHODS: Wistar rats were divided into a normal liver group (N group) and a mild ...AIM: To investigate the effect of mild steatotic liver on ischemia-reperfusion injury by focusing on Kupffer cells (KCs) and platelets. METHODS: Wistar rats were divided into a normal liver group (N group) and a mild steatotic liver group (S group) induced by feeding a choline-deficient diet for 2 wk. Both groups were subjected to 20 min of warm ischemia followed by 120 min of reperfusion. The number of labeled KCs and platelets in sinusoids and the blood perfusion in sinusoids were observed by intravital microscopy (IVM), which was performed at 30, 60 and 120 min after reperfusion. To evaluate serum alanine aminotransferase as a marker of liver deterioration, blood samples were taken at the same time as IVM.RESULTS: In the S group, the number of platelets adhering to KCs decreased significantly compared with the N group (120 after reperfusion; 2.9±1.1 cells/acinus vs 4.8±1.2 cells/acinus, P<0.01). The number of KCs in sinusoids was significantly less in the S group than in the N group throughout the observation periods (before ischemia, 19.6±3.3 cells/acinus vs 28.2±4.1 cells/acinus, P<0.01 and 120 min after reperfusion, 29.0±4.3 cells/acinus vs 40.2±3.3 cells/acinus, P<0.01). The blood perfusion of sinusoids 120 min after reperfusion was maintained in the S group more than in the N group. Furthermore, elevation of serum alanine aminotransferase was lower in the S group than in the N group 120 min after reperfusion (99.7±19.8 IU/L vs 166.3±61.1 IU/L, P=0.041), and histological impairment of hepatocyte structure was prevented in the S group. CONCLUSION: Ischemia-reperfusion injury in mild steatotic liver was attenuated compared with normal liver due to the decreased number of KCs and the reduction of the KC-platelet interaction.展开更多
Major depression is an independent risk factor for cardiovascular mortality and morbidity. The exact mechanisms linking depression and increased cardiovascular risk remain poorly understood. Several mechanisms have be...Major depression is an independent risk factor for cardiovascular mortality and morbidity. The exact mechanisms linking depression and increased cardiovascular risk remain poorly understood. Several mechanisms have been proposed including increased platelet reactivity. This review focuses on the current literature that examines the platelet hypothesis of depression. To date studies show increased serotonin response, increased platelet serotonin receptor density, decreased serotonin transporter binding, and decreased platelet serotonin levels in individuals with depression. However other studies have shown no change in serotonin uptake. In addition to platelet serotonin specific pathways, other platelet pathways that have shown significant changes in depressed individuals include blunting of the platelet adenosine response, increased platelet thrombin response, increased glycoprotein Ⅰb expression, increased P-selectin, β thromboglobulin, and platelet factor four, as well as decreased platelet brain derived neurotrophic factor. However there are other studies that show conflicting evidence of increased platelet activation as measured by integrin receptor α2b β3. Other conflictingdata include α adrenergic density and platelet response to augmented serotonin. The direction of future research in platelet functional changes in depression and coronary artery disease should continue to focus on serotonin specific pathways with emphasis on potential mechanisms of specific pathway changes.展开更多
Single-crystal alpha alumina （α-Al2O3） platelets were synthesized by calcining a powder mixture of bayerite （α-AI（OH）3） and potassium sulfate （K2SO4） at 900℃. The crystalline phase evolutions and morphologi...Single-crystal alpha alumina （α-Al2O3） platelets were synthesized by calcining a powder mixture of bayerite （α-AI（OH）3） and potassium sulfate （K2SO4） at 900℃. The crystalline phase evolutions and morphologies of the samples were characterized by X-ray diffraction （XRD）, scanning electron microscopy （SEM）, and transmission electron microscopy （TEM）. The synthesized samples mainly consisted of single-crystal α-Al2O3 platelets with a diameter of 0.5-1.5 μm and a thickness of 50-150 nm. Moreover, with 3, 5, and 8 wt% （referred to the obtained alumina） α-Al2O3 seeds adding into the powder mixture of bayerite and potassium sulfate, the average diameter of α-Al2O3 platelets can be reduced to 450, 240, and 220 nm, respectively. It is found that the sequence of the phase transformation is the bayerite （α-Al（OH）3） → boehmite （γ-AIOOH） →γ-Al2O3 → α-Al2O3. Further analysis indicated that K2SO4 can promote the phase transformation from α-Al2O3 to α-Al2O3 and the formation of single-crystal α-Al2O3 platelets might be attributed to the liquid phase K3AI（SO4）3.展开更多
Metastasis is the main cause of cancer-associated mortality. During this complicated process, some cancer cells, also called circulating tumor cells （CTCs）, detach from primary sites, enter bloodstream and extravasa...Metastasis is the main cause of cancer-associated mortality. During this complicated process, some cancer cells, also called circulating tumor cells （CTCs）, detach from primary sites, enter bloodstream and extravasate at metastatic site. Thrombocytosis is frequently observed in patients with metastatic cancers suggesting the important role of platelets in metastasis. Therefore this review focuses on how platelets facilitate the generation of CTCs, protect them from various host attacks, such as immune assaults, apoptosis and shear stress, and regulate CTCs intravasation/extravasation. Platelet-derived cytokines and receptors are involved in this cascade. Identification the mechanisms underlie platelet-CTCs interactions could lead to the development of new platelet-targeted therapeutic strategy to reduce metastasis.展开更多
Although viral hepatitis treatments have evolved over the years, the resultant liver cirrhosis still does not completely heal. Platelets contain proteins required for hemostasis, as well as many growth factors require...Although viral hepatitis treatments have evolved over the years, the resultant liver cirrhosis still does not completely heal. Platelets contain proteins required for hemostasis, as well as many growth factors required for organ development, tissue regeneration and repair. Thrombocytopenia, which is frequently observed in patients with chronic liver disease(CLD) and cirrhosis, can manifest from decreased thrombopoietin production and accelerated platelet destruction caused by hypersplenism; however, the relationship between thrombocytopenia and hepatic pathogenesis, as well as the role of platelets in CLD, is poorly understood. In this paper, experimental evidence of platelets improving liver fibrosis and accelerating liver regeneration is summarized and addressed based on studies conducted in our laboratory and current progress reports from other investigators. In addition, we describe our current perspective based on the results of these studies. Platelets improve liver fibrosis by inactivating hepatic stellate cells, which decreases collagen production. The regenerative effect of platelets in the liver involves a direct effect on hepatocytes, a cooperative effect with liver sinusoidal endothelial cells, and a collaborative effect with Kupffer cells. Based on these observations, we ascertained the direct effect of platelet transfusion on improving several indicators of liver function in patients with CLD and liver cirrhosis. However, unlike the results of our previous clinical study, the smaller incremental changes in liver function in patients with CLD who received eltrombopag for 6 mo were due to patient selection from a heterogeneous population. We highlight the current knowledge concerning the role of platelets in CLD and cancer and anticipate a novel application of platelet-based clinical therapies to treat liver disease.展开更多
Schizophrenia is a severe mental disorder, characterized by behavioral, emotional and cognitive disturbances,which commonly follows a chronic course. Diagnostic accuracy, management plans, treatment evaluation and pro...Schizophrenia is a severe mental disorder, characterized by behavioral, emotional and cognitive disturbances,which commonly follows a chronic course. Diagnostic accuracy, management plans, treatment evaluation and prognosis are dependent on relatively subjective assessments. Despite extensive research and improvement in imaging technology, as well as modern genetic and molecular methodologies, the biological basis of this disease is still unclear. Therefore, there is a need for objective and valid biological markers. Platelets have often been used as a model in neurobiological research. The accessibility of platelets and their similarities with neurons turns them into an attractive candidate to search for biological markers for diagnosis and for unraveling pathophysiological processes relevant to the etiology of brain disorders, including schizophrenia.The present review addresses the main changes in platelet physiology observed in schizophrenia and its response to antipsychotic medication. We summarize numerous studies demonstrating impaired metabolism,uptake and receptor kinetics of schizophrenia-relevantneurotransmitters, abnormalities in membrane derived phospholipids and polyunsaturated fatty acids, as well as dysfunctions in the mitochondria. These changes fit with the various hypotheses raised for the etiology of schizophrenia, including the dopamine-glutamate hypothesis, the autoimmune hypothesis, the polyunsaturated fatty acid hypothesis and the impaired energy metabolism hypothesis. Despite extensive research in platelets, no conclusive reliable biomarker has been identified yet. This review suggests that the clinical heterogeneity and the biological complexity of schizophrenia lead to the inevitable conclusion that biomarkers will be identified only for subgroups characterized according to the different diagnostic criteria. Moreover, any biomarker would have to be an array of interrelated factors or even a set of several such arrays.展开更多
BACKGROUND Platelets have been reported to participate in tumor cell growth,extravasation,epithelial–mesenchymal transition,metastasis,and drug resistance.However,the importance of platelets in pancreatic neuroendocr...BACKGROUND Platelets have been reported to participate in tumor cell growth,extravasation,epithelial–mesenchymal transition,metastasis,and drug resistance.However,the importance of platelets in pancreatic neuroendocrine tumor(pNET)lacks adequate literature support.The predictive value of tumor-infiltrating platelets(TIPs)in pNET remains unclear.AIM To investigate the relationship between TIPs and the prognosis of patients with pNET following radical resection.METHODS In total,113 patients who had undergone radical surgical resection with a pathologic diagnosis of pNET were enrolled in this study.Immunohistochemical analysis of cluster of differentiation 42b(CD42b)expression in the tumor specimens was performed to determine the presence of TIPs.Univariate and multivariate analyses were used to analyze the prognostic value of TIPs.RESULTS TIPs were observed in intratumoral areas in 54 patients.Neither basic characteristics nor preoperative platelet-associated indicators showed a significant relationship with the presence of TIPs(all P>0.05).Patients with positive intratumoral CD42b expression had worse overall survival(P=0.005)and recurrence-free survival(P<0.001)than those with negative intratumoral CD42b expression.Multivariate analysis demonstrated that TIPs were independent prognostic factors for overall survival(P=0.049)and recurrencefree survival(P=0.003).Nevertheless,platelet count,mean platelet volume,and platelet-to-lymphocyte ratio were not associated with postoperative survival or recurrence in pNET patients(all P>0.05).CONCLUSION TIPs are a useful prognostic biomarker for patients with resectable pNET,and their detection represents a promising tool for pNET treatment strategy decisions.展开更多
OBJECTIVE:To investigate whether cancer stem cells(CSCs) more efficiently activating platelets and evading immune surveillance than non-CSCs thus promoting metastasis.METHODS:We enriched and identified sphereforming c...OBJECTIVE:To investigate whether cancer stem cells(CSCs) more efficiently activating platelets and evading immune surveillance than non-CSCs thus promoting metastasis.METHODS:We enriched and identified sphereforming cells(SFCs) and coincubated washed platelets with several platelet activators including collagen,4T1 and SFCs.Platelet-coating tumor cells,platelet activation and TGF-β1 release were analyzed.Then natural kell cells(NK) were incubated with supernatants of different activated platelet samples what we called sample release(SR).The degranulation assay and NKG2 D expression on NK cells were conducted by flow cytometry.Finally tissue factor(TF) expression of SFCs or 4T1 were evaluated by western blot.RESULTS:Breast cancer cell line 4T1 could form spheres in serum-free medium at low adherence.Sphere-forming cells expressed high levels of the CD24-/lowCD44 + stem cell phenotype.Both sphere-forming cells or 4T1 were coated with abundant platelets while sphere-forming cells induced significantly higher expression of platelet activating receptor CD62 p than 4T1 did(P < 0.01).And sphere-forming cells induced platelets to produce more TGF-β1 than 4T1 did(P < 0.01).Furthermore,sample releases induced by sphere-forming cells caused more vigorous inhibition of NK cells antitumor reactivity(P < 0.05) and reduced NKG2 D expression(P < 0.01).The final results showed that sphere-forming cells expressed higher levels of TF than 4T1(P < 0.05).CONCLUSION:Our findings indicate that CSCs could efficiently activate platelets,induce platelets to secrete more TGF-β1,decrease NKG2 D expression and inhibit antitumor activity of NK cell,compared with 4T1.And higher levels of TF expression of CSCs may account for this correlation of CSCs and platelets.展开更多
The effects of different additives on the mechanical properties, microstructures, and wear behavior of corundum abra- sives were investigated. When the number of additive phases increases, the sintering temperature an...The effects of different additives on the mechanical properties, microstructures, and wear behavior of corundum abra- sives were investigated. When the number of additive phases increases, the sintering temperature and wear rate decrease, while the densification and mechanical properties increase. The additive SiO2 is responsible for the development of equiaxed grains, whereas both CaO and MgO promote the development of platelike grains. By controlling the molar ratio of additives, it is pos- sible to obtain different microstructures. With SiO2-MgO-CaO （molar ratio, 2：1：1） as the additives and nano a-Al203 powders as the seed, microcrystalline corundum abrasives with hexagonal platelets were obtained using sol-gel process by sintering at 1300℃ for 0.5 h. The average diameter and thickness of hexagonal platelets are 1.38 μm and 360 nm respectively, the sin- gle-particle compressive strength is 26.44 N, and the wear rate is （3.06±=0.21）× 10^-7 mm^3/（N.m）.展开更多
Angiotensin II (Ang II) is a critical component of the reninangiotensin system that contributes to hypertension. Although platelets in blood from hypertensive subjects have an abnormal biological profile, it is unclea...Angiotensin II (Ang II) is a critical component of the reninangiotensin system that contributes to hypertension. Although platelets in blood from hypertensive subjects have an abnormal biological profile, it is unclear if circulating Ang II influences platelet aggregation or thrombus formation. One of the abnormalities presented to the platelets during hypertension is an elevated plasma concentration of serotonin (5-HT) caused by reduced 5-HT uptake secondary to loss of the 5-HT transporter (SERT) on the platelet plasma membrane. In the current study, we evaluated in vivo platelet function after 7 days of subcutaneous Ang II infusion to establish hypertension in mice and additionally assessed the biology of isolated platelets exposed to Ang II in vitro. The administration of Ang II elevated systolic blood pressure, but markers of platelet activation including P-selectin and PEJon/A staining were not changed. However, the aggregation response to collagen was reduced in isolated platelets from Ang II-infused mice, which also showed reduced 5-HT uptake by SERT. In vitro exposure of isolated platelets to Ang II also resulted in a loss of surface SERT associated with a reduced aggregation response to collagen. These abnormalities were reversed by increasing concentra tions of the Ang II receptor antagonist, valsartan. Interestingly, SERT KO mice failed to fully develop hypertension in response to Ang II infusion and isolated platelets from these animals were insensitive to the anti-aggregatory influence of Ang II. Thus, Ang II blunts the aggregation responses of platelets and the mechanism underlying this action may involve a loss of SERT on the platelet plasma membrane. The latter event depletes intracellular 5-HT in platelets, an event that is associated with reduced aggregation. The widespread use of antihypertensive drugs that target the renin-angiotensin system suggest the potential clinical utility of our findings and emphasize the importance of understanding the impact of Ang II on platelet function.展开更多
Platelets are the first peripheral source of amyloid precursor protein(APP). They possess the proteolytic machinery to produce Aβ and fragments similar to those produced in neurons, and thus offer an ex-vivo model to...Platelets are the first peripheral source of amyloid precursor protein(APP). They possess the proteolytic machinery to produce Aβ and fragments similar to those produced in neurons, and thus offer an ex-vivo model to study APP processing and changes associated with Alzheimer's disease(AD). Platelet process APP mostly through the α-secretase pathway to release soluble APP(s APP). They produce small amounts of Aβ, predominantly Aβ40 over Aβ42. s APP and Aβ are stored inα-granules and are released upon platelet activation by thrombin and collagen, and agents inducing platelet degranulation. A small proportion of full-length APP is present at the platelet surface and this increases by 3-fold upon platelet activation. Immunoblotting of platelet lysates detects APP as isoforms of 130 kD a and106-110 kD a. The ratio of these of APP isoforms is significantly lower in patients with AD and mild cognitive impairment(MCI) than in healthy controls. This ratio follows a decrease that parallels cognitive decline andcan predict conversion from MCI to AD. Alterations in the levels of α-secretase ADAM10 and in the enzymatic activities of α- and β-secretase observed in platelets of patients with AD are consistent with increased processing through the amyloidogenic pathway. β-APP cleaving enzyme activity is increased by 24% in platelet membranes of patients with MCI and by 17% in those with AD. Reports of changes in platelet APP expression with MCI and AD have been promising so far and merit further investigation as the search for blood biomarkers in AD, in particular at the prodromal stage, remains a priority and a challenge.展开更多
Objective: To study the effects of total flavone of Abelmoschl Manihot L.Medic (TFA) on the function of platelets and to explore its mechanism. Methods: Rat models of artery-veins bypassing thrombus formation were use...Objective: To study the effects of total flavone of Abelmoschl Manihot L.Medic (TFA) on the function of platelets and to explore its mechanism. Methods: Rat models of artery-veins bypassing thrombus formation were used. The platelets of rabbits were collected. Platelet aggregation was induced by collagen and intracellular calcium ion concentration ([Ca 2+ ]i) was assayed by Fura-2 method. Results: TFA (25, 50, 100 mg/kg) significantly and dose-dependently reduced the weight of thrombus. TFA (0.025, 0.05, 0.1 mg/ml) possessed dose-dependant inhibitory effects on rabbits' platelet aggregation induced by collagen. TFA significantly reduced the resting and CaCl 2-induced increase of free intracellular calcium concentration ([Ca 2+ ]i) in rabbit platelet in vitro . Conclusion: TFA has an antiplatelet effect via the inhibition on the influx of Ca 2+ .展开更多
A rehydration process for freeze-dried human platelets was studied on 1 ml of samples. The effects of prehydration duration, prehydration temperature, an rehydration solution on the recovery rate, mean platelet volume...A rehydration process for freeze-dried human platelets was studied on 1 ml of samples. The effects of prehydration duration, prehydration temperature, an rehydration solution on the recovery rate, mean platelet volume （MPV）, and platelet distribution width （PDW） were investigated. The mass changes during the prehydration process were also studied. Three prehydration durations： 0, 1.5, and 3.5 h, and two rehydration solutions： platelet-poor plasma and phosphate-buffered saline （PBS）, were tested. It was found that： （1） the prehydration was of significance; （2） 1.5 h of prehydration had better effects than 3.5 h of prehydration; （3） as a rehydration solution, the platelet-poor plasma behaved better than the PBS. The impacts of prehydration duration and temperature on the results were studied. There was almost no difference between 35 and 37 ℃. Among all the prehydration durations tested, 15, 30, 60, 90, and 120 min, the best result was achieved with the time duration of 15 min. The weights of prehydrated platelets at the end of each test were measured and the water contents were calculated. After 15 min ofprehydration, the water contents in the samples were about （4.8±0.01）% and （5.27±0.29）% （w/w） corresponding to the conditions of 35 and 37 ℃, respectively. These results will be helpful for further studies on the freeze-drying of mammalian cells.展开更多
The inhibition of specific flavonoid on the in vitro platelet aggregation induced by collagen, arachidonic acid and thromboxane A2 (TxA2) agonist, seems to be related mostly to their ability to compete for binding to ...The inhibition of specific flavonoid on the in vitro platelet aggregation induced by collagen, arachidonic acid and thromboxane A2 (TxA2) agonist, seems to be related mostly to their ability to compete for binding to the TxA2 receptor (TP). The aim of this study was to analyze the effect of soy isoflavone and equol in terms of inhibiting the platelet aggregation and sCD40L release stimulated by ristocetin, an in vitro-activator of glycoprotein Ib/IX/V, in platelets from postmenopausal women. When platelets were stimulated by 0.75 mg/ml ristocetin, equol (10 μM) exhibited a greater inhibitory activity on platelet aggregation (~68%) than genistein or daidzein. The effect of equol was dependent on the concentration of platelet aggregation agonist. In the presence of ristocetin (0.75 mg/ml, 1.125 mg/ml and 1.5 mg/ml), the inhibitory effect of 10 μM equol was 68% ± 5%, 54% ± 4% and 31% ± 5%, respectively. Equol (10 μM) was a potent inhibitor (~35%) of sCD40L release when stimulated with 1.5 mg/ml ristocetin. However, no significant differences were noted in platelets incubated in the presence of genistein or daidzein and stimulated by ristocetin. On the other hand, SQ29548, a high TP antagonist, also inhibited the sCD40L release stimulated by ristocetin. Finally, 10 μM of genistein, daidzein or equol did not significantly affect the thromboxane B2 production when platelets were incubated with 1.5 mg/ml ristocetin. The relevance of this study was to find that equol exhibits a potent activity by inhibiting ristocetin-induced sCD40L release, suggesting that soy isoflavone has important biological effects on the hemostatic system. However, clinical trials will be necessary to assess the effect of equol on platelet and their impact on inflammatory markers.展开更多
Well-crystallized hexagonal hematite （α-Fe2O3） platelets were synthesized by hydrothermal process, using a highly concentrated ferric hydroxide as precursor. The precursor was prepared by adding ammonia to the ferr...Well-crystallized hexagonal hematite （α-Fe2O3） platelets were synthesized by hydrothermal process, using a highly concentrated ferric hydroxide as precursor. The precursor was prepared by adding ammonia to the ferric sulfate solution which was obtained by leaching pyrite cinders with sulfuric acid. Structure and morphology of the synthesized products were investigated by X-ray diffraction, scanning electron microscope, transmission electron microscope and selected area electron diffraction. The results reveal that the reaction temperature has significant effects on the structure, size and shape of the synthesized hematite particles. Typical hexagonal hematite platelets, about 0.4-0.6 μm in diameter and 0.1 μm in thickness, were prepared at 230 ℃ for 0.5 h. Al^3＋, contained in the sulfuric acid leaching solution as an impurity, plays an extremely important role in the formation of hexagonal hematite. In addition, a possible mechanism about the formation of hexagonal hematite platelets was proposed.展开更多
文摘Platelet indices(PIs)including high mean platelet volume(MPV),plateletcrit(PLC),and platelet distribution width(PLDW)are associated with poor glycemic control.In addition,they can indicate prothrombotic and procoagulation risk among patients with diabetes.PI measurement is cheap,quick and fits healthcare system needs in remote outreaching areas in low-income countries.However,a broader insight into their clinical implications in diabetes is lacking.To achieve a wider understanding,we reviewed PubMed/MEDLINE,Google Scholar and Cochrane Library for relevant articles investigating the role of PIs in diabetes mellitus.No limitation to the publication date was applied,which included all articles published up to August 17,2024.The terms used were MPV,PLC,PLDW,platelet large cell ratio,glycated hemoglobin(HbA1c),PIs,platelet activity and diabetes mellitus.Out of the 790 articles retrieved,187 full texts were reviewed,and 44 were included.PIs,when measurements are done promptly and within 2 h,could be short-term pointers to glycemic control in the life span of the platelets(2 wk).PIs are easy to perform,cheap and useful in remote outreaching areas with limited facilities where measurement of HbA1c is not available or cost-effective.However,PIs are not specific and are affected by demographic factors,such as pregnancy,renal failure,medications,hemoglobin and duration of diabetes.PIs could be implemented with daily blood glucose to inform doctors in low-income countries about their patients'glycemic control and cardiovascular risk.An important application might be when blood glucose control is needed quickly(before elective surgery).
基金supported by the the National Key R&D Program of China(2024YFC2310000)the Key Project of Key Laboratory of VirologyBiosafety in the Wuhan Institute of Virology,Chinese Academy of Sciences(2024JZZD-02),the Youth Project of the Wuhan Institute of Virology,Chinese Academy of Sciences(2023QNTJ-03)+2 种基金the"Open Competition for Selecting the Best Candidates"Project of the Wuhan East Lake New Technology Development Zone(2022KJB117)the Natural Science Foundation of Hubei Province(2024AFB986)the Medical Science Research Project of Wuhan Health Commission(WX23B09).
文摘Crimean-Congo hemorrhagic fever(CCHF)is a hemorrhagic fever caused by infection with the CCHF virus(CCHFV)and has a mortality rate of up to 30%.Thrombocytopenia is a hallmark of CCHF;however,the mechanisms underlying this manifestation remain poorly understood.In addition to hemostasis,platelets play a crucial role in recognizing pathogens and mediating immune responses.We investigated the mechanisms underlying thrombocytopenia associated with CCHFV infection by analyzing the platelet transcriptome in mice.Interferon-induced transmembrane protein 3(IFITM3),a known antiviral factor,was significantly upregulated.The role of IFITM3 in response to CCHFV infection was characterized using the human megakaryoblast cell line MEG-01,considered a parental cell line of platelets.Although the CCHFV infection rate was limited,MEG-01 cells maintained the infection and replication of CCHFV,leading to increased IFITM3 protein expression.We demonstrated that IFITM3 overexpression efficiently inhibited CCHFV infection,whereas IFITM3 knockout promoted viral infection.An interaction between IFITM3 and the CCHFV glycoprotein Gc was identified,which suppressed CCHFV entry into cells.The IFITM3 CIL-TMD domain is critical for this interaction.These results suggest that IFITM3 is a restriction factor and plays an antiviral role during CCHFV infection.Elevated expression of IFITM3 in platelets indicates that this could be a common mechanism by which platelets protect against viruses,including CCHFV,which may reduce platelet consumption and destruction caused by CCHFV infection.These findings provide valuable insights into the pathogenesis of CCHF-associated thrombocytopenia and offer foundational theoretical support for future therapeutic strategies.
基金supported in part by Canadian Institutes of Health Research(MOP 119540),National Natural Science Foundation of China-Canadian Institutes of Health Research(China-Canada Joint Health Research Initiative Program),Heart and Stroke Foundation of Canada(Ontario)supported by equipment Funds from St.Michael's Hospital,Canadian Blood Services,and Canada Foundation for Innovation
文摘Platelets are small anucleate cells generated from megakaryocytes in the bone marrow. Although platelet genera- tion, maturation, and clearance are still not fully understood, significant progress has been made in the last 1-2 dec- ades. In blood circulation, platelets can quickly adhere and aggregate at sites of vascular injury, forming the platelet plug （i.e. the first wave of hemostasis）. Activated platelets can also provide negatively charged phosphatidylserine- rich membrane surface that enhances cell-based thrombin generation, which facilitates blood coagulation （i.e. the second wave of hemostasis）. Platelets therefore play central roles in hemostasis. However, the same process of hemostasis may also cause thrombosis and vessel occlusion, which are the most common mechanisms leading to heart attack and stroke following ruptured atherosclerotic lesions. In this review, we will introduce the classical mechanisms and newly discovered pathways of platelets in hemostasis and thrombosis, including fibrinogen-inde- pendent platelet aggregation and thrombosis, and the plasma fibronectin-mediated ＂protein wave＂ of hemostasis that precedes the classical first wave of hemostasis. Furthermore, we briefly discuss the roles of platelets in inflam- marion and atherosclerosis and the potential strategies to control atherothrombosis.
基金Supported by Research grants from University of Tsukubathe Basic Research Support Program for Young Researcher
文摘AIM:To investigate the role of human platelets in liver fibrosis.METHODS:Severe combined immunodeficiency(SCID)mice were administered CCl4and either phosphate-buffered saline(PBS group)or human platelet transfusions(hPLT group).Concentrations of hepatocyte growth factor(HGF),matrix metallopeptidases(MMP)-9,and transforming growth factor-β(TGF-β)in the liver tissue were compared between the PBS and the hPLT groups by enzyme-linked immunosorbent assay(ELISA)and Western blotting.The effects of a human platelet transfusion on liver fibrosis included the fibrotic area,hydroxyproline content,and-smooth muscle actin(α-SMA)expression,which were evaluated by picrosirius red staining,ELISA,and immunohistochemical staining using an anti-mouse-SMA antibody,respectively.Phosphorylations of mesenchymal-epithelial transition factor(Met)and SMAD3,downstream signals of HGF and TGF-β,were compared between the two groups by Western blotting and were quantified using densitometry.Hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase dUTP nick end labeling.Furthermore,the accumulation of human platelets in the liver 2 h after platelet transfusion was compared between normal and fibrotic livers by immunohistochemical staining using an anti-human CD41 antibody.RESULTS:The fibrotic area and hydroxyproline content in the liver were both significantly lower in the hPLT group when compared to the PBS group(fibrotic area,1.7%±0.6%vs 2.5%±0.6%,P=0.03;hydroxyproline content,121±26 ng/g liver vs 156±47 ng/g liver,P=0.04).There was less α-smooth muscle actin staining in the hPLT group than in the PBS group(0.5%±0.1%vs 0.8%±0.3%,P=0.02).Hepatic expression levels of mouse HGF and MMP-9were significantly higher in the hPLT group than in the PBS group(HGF,109±13 ng/g liver vs 88±22 ng/g liver,P=0.03;MMP-9,113%±7%/GAPDH vs 92%±11%/GAPDH,P=0.04).In contrast,the concentration of mouse TGF-β in the liver tissue was significantly lower in the hPLT group than in the PBS group(22±5ng/g liver vs 39±6 ng/g liver,P=0.02).Phosphorylation of Met was more prevalent in the hPLT group than in the PBS group(37%±4%/GAPDH vs 20%±8%/GAPDH,P=0.03).Phosphorylation of SMAD3was weaker in the hPLT group than in the PBS group(60%±12%/GAPDH vs 84%±12%/GAPDH,P=0.1),although this difference was not significant.Furthermore,a lower rate of hepatocyte apoptosis was observed in the hPLT group than in the PBS group(5.9%±1.7%vs 2.9%±2.1%,P=0.02).Significant human platelet accumulation was observed in the fibrotic liver tissues,whereas few platelets accumulated in the normal liver.CONCLUSION:Human platelets inhibit liver fibrosis in SCID mice.Increased concentration of HGF in the liver suppresses hepatic stellate cell activation,induces MMPs,and inhibits hepatocyte apoptosis.
文摘There is evidence that inflammatory bowel diseases (IBD) combine both inflammation and coagulation in their pathogenesis and clinical manifestations. Although platelets (PLT) are well known for their role in hemostasis, there are a rising number of studies supporting their considerable role as inflammatory amplifiers in chronic inflammatory conditions. IBD are associated with several alterations of PLT, including number, shape, and function, and these abnormalities are mainly attributed to the highly activated state of circulating PLT in IBD patients. When PLT activate, they increase in size, release a great variety of bio-active inflammatory and procoagulant molecules/particles, and express a variety of inflammatory receptors. These inflammatory products may represent a part of the missing link between coagulation and inflammation, and can be considered as possible IBD pathogenesis instigators. In clinical practice, thrombocytosis is associated both with disease activity and iron deficiency anemia. Controlling inflammation and iron replacement in anemic patients usually leads to a normalization of PLT count. The aim of this review is to update the role of PLT in IBD and present recent data revealing the possible therapeutic implications of anti-PLT agents in future IBD remedies.
基金Supported by The Ministry of Education, Culture, Sports, Science, and Technology of Japan, KAKENHI, No. 22591499
文摘AIM: To investigate the effect of mild steatotic liver on ischemia-reperfusion injury by focusing on Kupffer cells (KCs) and platelets. METHODS: Wistar rats were divided into a normal liver group (N group) and a mild steatotic liver group (S group) induced by feeding a choline-deficient diet for 2 wk. Both groups were subjected to 20 min of warm ischemia followed by 120 min of reperfusion. The number of labeled KCs and platelets in sinusoids and the blood perfusion in sinusoids were observed by intravital microscopy (IVM), which was performed at 30, 60 and 120 min after reperfusion. To evaluate serum alanine aminotransferase as a marker of liver deterioration, blood samples were taken at the same time as IVM.RESULTS: In the S group, the number of platelets adhering to KCs decreased significantly compared with the N group (120 after reperfusion; 2.9±1.1 cells/acinus vs 4.8±1.2 cells/acinus, P<0.01). The number of KCs in sinusoids was significantly less in the S group than in the N group throughout the observation periods (before ischemia, 19.6±3.3 cells/acinus vs 28.2±4.1 cells/acinus, P<0.01 and 120 min after reperfusion, 29.0±4.3 cells/acinus vs 40.2±3.3 cells/acinus, P<0.01). The blood perfusion of sinusoids 120 min after reperfusion was maintained in the S group more than in the N group. Furthermore, elevation of serum alanine aminotransferase was lower in the S group than in the N group 120 min after reperfusion (99.7±19.8 IU/L vs 166.3±61.1 IU/L, P=0.041), and histological impairment of hepatocyte structure was prevented in the S group. CONCLUSION: Ischemia-reperfusion injury in mild steatotic liver was attenuated compared with normal liver due to the decreased number of KCs and the reduction of the KC-platelet interaction.
文摘Major depression is an independent risk factor for cardiovascular mortality and morbidity. The exact mechanisms linking depression and increased cardiovascular risk remain poorly understood. Several mechanisms have been proposed including increased platelet reactivity. This review focuses on the current literature that examines the platelet hypothesis of depression. To date studies show increased serotonin response, increased platelet serotonin receptor density, decreased serotonin transporter binding, and decreased platelet serotonin levels in individuals with depression. However other studies have shown no change in serotonin uptake. In addition to platelet serotonin specific pathways, other platelet pathways that have shown significant changes in depressed individuals include blunting of the platelet adenosine response, increased platelet thrombin response, increased glycoprotein Ⅰb expression, increased P-selectin, β thromboglobulin, and platelet factor four, as well as decreased platelet brain derived neurotrophic factor. However there are other studies that show conflicting evidence of increased platelet activation as measured by integrin receptor α2b β3. Other conflictingdata include α adrenergic density and platelet response to augmented serotonin. The direction of future research in platelet functional changes in depression and coronary artery disease should continue to focus on serotonin specific pathways with emphasis on potential mechanisms of specific pathway changes.
基金supported by the National Natural Science Foundation of China (Grant Nos. 51102022 and 50872046)the China Postdoctoral Science Foundation (Grant No. 2011M501413)+1 种基金the Special Fund for Basic Scientific Research of Central Colleges, Changan University (Grant No. CHD2012ZD015)the Special Fund for Basic Research support programs of Chang an Univer sity
文摘Single-crystal alpha alumina （α-Al2O3） platelets were synthesized by calcining a powder mixture of bayerite （α-AI（OH）3） and potassium sulfate （K2SO4） at 900℃. The crystalline phase evolutions and morphologies of the samples were characterized by X-ray diffraction （XRD）, scanning electron microscopy （SEM）, and transmission electron microscopy （TEM）. The synthesized samples mainly consisted of single-crystal α-Al2O3 platelets with a diameter of 0.5-1.5 μm and a thickness of 50-150 nm. Moreover, with 3, 5, and 8 wt% （referred to the obtained alumina） α-Al2O3 seeds adding into the powder mixture of bayerite and potassium sulfate, the average diameter of α-Al2O3 platelets can be reduced to 450, 240, and 220 nm, respectively. It is found that the sequence of the phase transformation is the bayerite （α-Al（OH）3） → boehmite （γ-AIOOH） →γ-Al2O3 → α-Al2O3. Further analysis indicated that K2SO4 can promote the phase transformation from α-Al2O3 to α-Al2O3 and the formation of single-crystal α-Al2O3 platelets might be attributed to the liquid phase K3AI（SO4）3.
基金supported by grants from the National Natural Science Foundation of China(No. 81300347)the Natural Science Foundation of Jiangxi Province,China(No.20132BAB205037,20151BAB215008, 20151BBG70200)+1 种基金Foundation of Jiangxi Educational Committee(No.GJJ14192)Foundation of Health and Family Planning Commission of Jiangxi Province(No. 20155592,20155103)
文摘Metastasis is the main cause of cancer-associated mortality. During this complicated process, some cancer cells, also called circulating tumor cells （CTCs）, detach from primary sites, enter bloodstream and extravasate at metastatic site. Thrombocytosis is frequently observed in patients with metastatic cancers suggesting the important role of platelets in metastasis. Therefore this review focuses on how platelets facilitate the generation of CTCs, protect them from various host attacks, such as immune assaults, apoptosis and shear stress, and regulate CTCs intravasation/extravasation. Platelet-derived cytokines and receptors are involved in this cascade. Identification the mechanisms underlie platelet-CTCs interactions could lead to the development of new platelet-targeted therapeutic strategy to reduce metastasis.
文摘Although viral hepatitis treatments have evolved over the years, the resultant liver cirrhosis still does not completely heal. Platelets contain proteins required for hemostasis, as well as many growth factors required for organ development, tissue regeneration and repair. Thrombocytopenia, which is frequently observed in patients with chronic liver disease(CLD) and cirrhosis, can manifest from decreased thrombopoietin production and accelerated platelet destruction caused by hypersplenism; however, the relationship between thrombocytopenia and hepatic pathogenesis, as well as the role of platelets in CLD, is poorly understood. In this paper, experimental evidence of platelets improving liver fibrosis and accelerating liver regeneration is summarized and addressed based on studies conducted in our laboratory and current progress reports from other investigators. In addition, we describe our current perspective based on the results of these studies. Platelets improve liver fibrosis by inactivating hepatic stellate cells, which decreases collagen production. The regenerative effect of platelets in the liver involves a direct effect on hepatocytes, a cooperative effect with liver sinusoidal endothelial cells, and a collaborative effect with Kupffer cells. Based on these observations, we ascertained the direct effect of platelet transfusion on improving several indicators of liver function in patients with CLD and liver cirrhosis. However, unlike the results of our previous clinical study, the smaller incremental changes in liver function in patients with CLD who received eltrombopag for 6 mo were due to patient selection from a heterogeneous population. We highlight the current knowledge concerning the role of platelets in CLD and cancer and anticipate a novel application of platelet-based clinical therapies to treat liver disease.
文摘Schizophrenia is a severe mental disorder, characterized by behavioral, emotional and cognitive disturbances,which commonly follows a chronic course. Diagnostic accuracy, management plans, treatment evaluation and prognosis are dependent on relatively subjective assessments. Despite extensive research and improvement in imaging technology, as well as modern genetic and molecular methodologies, the biological basis of this disease is still unclear. Therefore, there is a need for objective and valid biological markers. Platelets have often been used as a model in neurobiological research. The accessibility of platelets and their similarities with neurons turns them into an attractive candidate to search for biological markers for diagnosis and for unraveling pathophysiological processes relevant to the etiology of brain disorders, including schizophrenia.The present review addresses the main changes in platelet physiology observed in schizophrenia and its response to antipsychotic medication. We summarize numerous studies demonstrating impaired metabolism,uptake and receptor kinetics of schizophrenia-relevantneurotransmitters, abnormalities in membrane derived phospholipids and polyunsaturated fatty acids, as well as dysfunctions in the mitochondria. These changes fit with the various hypotheses raised for the etiology of schizophrenia, including the dopamine-glutamate hypothesis, the autoimmune hypothesis, the polyunsaturated fatty acid hypothesis and the impaired energy metabolism hypothesis. Despite extensive research in platelets, no conclusive reliable biomarker has been identified yet. This review suggests that the clinical heterogeneity and the biological complexity of schizophrenia lead to the inevitable conclusion that biomarkers will be identified only for subgroups characterized according to the different diagnostic criteria. Moreover, any biomarker would have to be an array of interrelated factors or even a set of several such arrays.
基金Supported by grants from the National Science Foundation for Distinguished Young Scholars of China,No.81625016the National Natural Science Foundation of China,No.81871941,No.81872366,No.81827807,No.81802675,and No.81702341+1 种基金the Outstanding Academic Leader Program of the “Technological Innovation Action Plan” in Shanghai Science and Technology Commission,No.18XD1401200the Young Talented Specialist Training Program of Shanghai
文摘BACKGROUND Platelets have been reported to participate in tumor cell growth,extravasation,epithelial–mesenchymal transition,metastasis,and drug resistance.However,the importance of platelets in pancreatic neuroendocrine tumor(pNET)lacks adequate literature support.The predictive value of tumor-infiltrating platelets(TIPs)in pNET remains unclear.AIM To investigate the relationship between TIPs and the prognosis of patients with pNET following radical resection.METHODS In total,113 patients who had undergone radical surgical resection with a pathologic diagnosis of pNET were enrolled in this study.Immunohistochemical analysis of cluster of differentiation 42b(CD42b)expression in the tumor specimens was performed to determine the presence of TIPs.Univariate and multivariate analyses were used to analyze the prognostic value of TIPs.RESULTS TIPs were observed in intratumoral areas in 54 patients.Neither basic characteristics nor preoperative platelet-associated indicators showed a significant relationship with the presence of TIPs(all P>0.05).Patients with positive intratumoral CD42b expression had worse overall survival(P=0.005)and recurrence-free survival(P<0.001)than those with negative intratumoral CD42b expression.Multivariate analysis demonstrated that TIPs were independent prognostic factors for overall survival(P=0.049)and recurrencefree survival(P=0.003).Nevertheless,platelet count,mean platelet volume,and platelet-to-lymphocyte ratio were not associated with postoperative survival or recurrence in pNET patients(all P>0.05).CONCLUSION TIPs are a useful prognostic biomarker for patients with resectable pNET,and their detection represents a promising tool for pNET treatment strategy decisions.
基金Supported by the National Natural Science Foundation of China(the Research of Traditional Chinese Medicien Regulating the Tumor Metastasis due to Cancer Stem Cell Related Expression of TF and TF/FⅦSignal Pathway Based on Traditional Chinese Mediceory of"Fu Du",No.81273947)the International S&T Cooperation Program Office of China(Herbal Medicine with Different Treatment Principles on Regulating the Biological Behaviour of Cancer Stem Cells and its Regulatory Factors,No.2013DFA32540)
文摘OBJECTIVE:To investigate whether cancer stem cells(CSCs) more efficiently activating platelets and evading immune surveillance than non-CSCs thus promoting metastasis.METHODS:We enriched and identified sphereforming cells(SFCs) and coincubated washed platelets with several platelet activators including collagen,4T1 and SFCs.Platelet-coating tumor cells,platelet activation and TGF-β1 release were analyzed.Then natural kell cells(NK) were incubated with supernatants of different activated platelet samples what we called sample release(SR).The degranulation assay and NKG2 D expression on NK cells were conducted by flow cytometry.Finally tissue factor(TF) expression of SFCs or 4T1 were evaluated by western blot.RESULTS:Breast cancer cell line 4T1 could form spheres in serum-free medium at low adherence.Sphere-forming cells expressed high levels of the CD24-/lowCD44 + stem cell phenotype.Both sphere-forming cells or 4T1 were coated with abundant platelets while sphere-forming cells induced significantly higher expression of platelet activating receptor CD62 p than 4T1 did(P < 0.01).And sphere-forming cells induced platelets to produce more TGF-β1 than 4T1 did(P < 0.01).Furthermore,sample releases induced by sphere-forming cells caused more vigorous inhibition of NK cells antitumor reactivity(P < 0.05) and reduced NKG2 D expression(P < 0.01).The final results showed that sphere-forming cells expressed higher levels of TF than 4T1(P < 0.05).CONCLUSION:Our findings indicate that CSCs could efficiently activate platelets,induce platelets to secrete more TGF-β1,decrease NKG2 D expression and inhibit antitumor activity of NK cell,compared with 4T1.And higher levels of TF expression of CSCs may account for this correlation of CSCs and platelets.
文摘The effects of different additives on the mechanical properties, microstructures, and wear behavior of corundum abra- sives were investigated. When the number of additive phases increases, the sintering temperature and wear rate decrease, while the densification and mechanical properties increase. The additive SiO2 is responsible for the development of equiaxed grains, whereas both CaO and MgO promote the development of platelike grains. By controlling the molar ratio of additives, it is pos- sible to obtain different microstructures. With SiO2-MgO-CaO （molar ratio, 2：1：1） as the additives and nano a-Al203 powders as the seed, microcrystalline corundum abrasives with hexagonal platelets were obtained using sol-gel process by sintering at 1300℃ for 0.5 h. The average diameter and thickness of hexagonal platelets are 1.38 μm and 360 nm respectively, the sin- gle-particle compressive strength is 26.44 N, and the wear rate is （3.06±=0.21）× 10^-7 mm^3/（N.m）.
文摘Angiotensin II (Ang II) is a critical component of the reninangiotensin system that contributes to hypertension. Although platelets in blood from hypertensive subjects have an abnormal biological profile, it is unclear if circulating Ang II influences platelet aggregation or thrombus formation. One of the abnormalities presented to the platelets during hypertension is an elevated plasma concentration of serotonin (5-HT) caused by reduced 5-HT uptake secondary to loss of the 5-HT transporter (SERT) on the platelet plasma membrane. In the current study, we evaluated in vivo platelet function after 7 days of subcutaneous Ang II infusion to establish hypertension in mice and additionally assessed the biology of isolated platelets exposed to Ang II in vitro. The administration of Ang II elevated systolic blood pressure, but markers of platelet activation including P-selectin and PEJon/A staining were not changed. However, the aggregation response to collagen was reduced in isolated platelets from Ang II-infused mice, which also showed reduced 5-HT uptake by SERT. In vitro exposure of isolated platelets to Ang II also resulted in a loss of surface SERT associated with a reduced aggregation response to collagen. These abnormalities were reversed by increasing concentra tions of the Ang II receptor antagonist, valsartan. Interestingly, SERT KO mice failed to fully develop hypertension in response to Ang II infusion and isolated platelets from these animals were insensitive to the anti-aggregatory influence of Ang II. Thus, Ang II blunts the aggregation responses of platelets and the mechanism underlying this action may involve a loss of SERT on the platelet plasma membrane. The latter event depletes intracellular 5-HT in platelets, an event that is associated with reduced aggregation. The widespread use of antihypertensive drugs that target the renin-angiotensin system suggest the potential clinical utility of our findings and emphasize the importance of understanding the impact of Ang II on platelet function.
基金Supported by(in part)The Judith Jane Mason and Harold Stannett Williams Memorial Foundation(ANZ Mason Foundation)the National Health and Medical Research Council of Australia(NHMRC project 566520)
文摘Platelets are the first peripheral source of amyloid precursor protein(APP). They possess the proteolytic machinery to produce Aβ and fragments similar to those produced in neurons, and thus offer an ex-vivo model to study APP processing and changes associated with Alzheimer's disease(AD). Platelet process APP mostly through the α-secretase pathway to release soluble APP(s APP). They produce small amounts of Aβ, predominantly Aβ40 over Aβ42. s APP and Aβ are stored inα-granules and are released upon platelet activation by thrombin and collagen, and agents inducing platelet degranulation. A small proportion of full-length APP is present at the platelet surface and this increases by 3-fold upon platelet activation. Immunoblotting of platelet lysates detects APP as isoforms of 130 kD a and106-110 kD a. The ratio of these of APP isoforms is significantly lower in patients with AD and mild cognitive impairment(MCI) than in healthy controls. This ratio follows a decrease that parallels cognitive decline andcan predict conversion from MCI to AD. Alterations in the levels of α-secretase ADAM10 and in the enzymatic activities of α- and β-secretase observed in platelets of patients with AD are consistent with increased processing through the amyloidogenic pathway. β-APP cleaving enzyme activity is increased by 24% in platelet membranes of patients with MCI and by 17% in those with AD. Reports of changes in platelet APP expression with MCI and AD have been promising so far and merit further investigation as the search for blood biomarkers in AD, in particular at the prodromal stage, remains a priority and a challenge.
基金Supported by the Natural Science Fund of Anhui Province (No 99044433) Supported by the Nature and Science of Education Office of Anhui Province (No 2003 KJ 224)
文摘Objective: To study the effects of total flavone of Abelmoschl Manihot L.Medic (TFA) on the function of platelets and to explore its mechanism. Methods: Rat models of artery-veins bypassing thrombus formation were used. The platelets of rabbits were collected. Platelet aggregation was induced by collagen and intracellular calcium ion concentration ([Ca 2+ ]i) was assayed by Fura-2 method. Results: TFA (25, 50, 100 mg/kg) significantly and dose-dependently reduced the weight of thrombus. TFA (0.025, 0.05, 0.1 mg/ml) possessed dose-dependant inhibitory effects on rabbits' platelet aggregation induced by collagen. TFA significantly reduced the resting and CaCl 2-induced increase of free intracellular calcium concentration ([Ca 2+ ]i) in rabbit platelet in vitro . Conclusion: TFA has an antiplatelet effect via the inhibition on the influx of Ca 2+ .
基金supported by the National Natural Science Foundation of China (No. 50606032)the Science Foundation of Health Office of China (No. WKJ2005-2-037)
文摘A rehydration process for freeze-dried human platelets was studied on 1 ml of samples. The effects of prehydration duration, prehydration temperature, an rehydration solution on the recovery rate, mean platelet volume （MPV）, and platelet distribution width （PDW） were investigated. The mass changes during the prehydration process were also studied. Three prehydration durations： 0, 1.5, and 3.5 h, and two rehydration solutions： platelet-poor plasma and phosphate-buffered saline （PBS）, were tested. It was found that： （1） the prehydration was of significance; （2） 1.5 h of prehydration had better effects than 3.5 h of prehydration; （3） as a rehydration solution, the platelet-poor plasma behaved better than the PBS. The impacts of prehydration duration and temperature on the results were studied. There was almost no difference between 35 and 37 ℃. Among all the prehydration durations tested, 15, 30, 60, 90, and 120 min, the best result was achieved with the time duration of 15 min. The weights of prehydrated platelets at the end of each test were measured and the water contents were calculated. After 15 min ofprehydration, the water contents in the samples were about （4.8±0.01）% and （5.27±0.29）% （w/w） corresponding to the conditions of 35 and 37 ℃, respectively. These results will be helpful for further studies on the freeze-drying of mammalian cells.
文摘The inhibition of specific flavonoid on the in vitro platelet aggregation induced by collagen, arachidonic acid and thromboxane A2 (TxA2) agonist, seems to be related mostly to their ability to compete for binding to the TxA2 receptor (TP). The aim of this study was to analyze the effect of soy isoflavone and equol in terms of inhibiting the platelet aggregation and sCD40L release stimulated by ristocetin, an in vitro-activator of glycoprotein Ib/IX/V, in platelets from postmenopausal women. When platelets were stimulated by 0.75 mg/ml ristocetin, equol (10 μM) exhibited a greater inhibitory activity on platelet aggregation (~68%) than genistein or daidzein. The effect of equol was dependent on the concentration of platelet aggregation agonist. In the presence of ristocetin (0.75 mg/ml, 1.125 mg/ml and 1.5 mg/ml), the inhibitory effect of 10 μM equol was 68% ± 5%, 54% ± 4% and 31% ± 5%, respectively. Equol (10 μM) was a potent inhibitor (~35%) of sCD40L release when stimulated with 1.5 mg/ml ristocetin. However, no significant differences were noted in platelets incubated in the presence of genistein or daidzein and stimulated by ristocetin. On the other hand, SQ29548, a high TP antagonist, also inhibited the sCD40L release stimulated by ristocetin. Finally, 10 μM of genistein, daidzein or equol did not significantly affect the thromboxane B2 production when platelets were incubated with 1.5 mg/ml ristocetin. The relevance of this study was to find that equol exhibits a potent activity by inhibiting ristocetin-induced sCD40L release, suggesting that soy isoflavone has important biological effects on the hemostatic system. However, clinical trials will be necessary to assess the effect of equol on platelet and their impact on inflammatory markers.
基金Project(2008A090300016) supported by the Key Science and Technology Item of Guangdong Province,ChinaProject(ZKJ2010022) supported by the Precious Apparatus Opening Center Foundation of Central South University,China
文摘Well-crystallized hexagonal hematite （α-Fe2O3） platelets were synthesized by hydrothermal process, using a highly concentrated ferric hydroxide as precursor. The precursor was prepared by adding ammonia to the ferric sulfate solution which was obtained by leaching pyrite cinders with sulfuric acid. Structure and morphology of the synthesized products were investigated by X-ray diffraction, scanning electron microscope, transmission electron microscope and selected area electron diffraction. The results reveal that the reaction temperature has significant effects on the structure, size and shape of the synthesized hematite particles. Typical hexagonal hematite platelets, about 0.4-0.6 μm in diameter and 0.1 μm in thickness, were prepared at 230 ℃ for 0.5 h. Al^3＋, contained in the sulfuric acid leaching solution as an impurity, plays an extremely important role in the formation of hexagonal hematite. In addition, a possible mechanism about the formation of hexagonal hematite platelets was proposed.
