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Eleutherococcus divaricatus (Siebold and Zucc.) S. Y. Hu. has been used in Traditional Chinese Medicine (TCM) due to its anticancer, immunostimulant, and anti-inflammatory activities. However, its mechanism of action and chemical composition are still insufficiently understood and require more advanced research, especially for cases in which anti-inflammatory properties are beneficial. The aim of this study was to evaluate the impact of E. divaricatus root extracts and fractions on proinflammatory serum hyaluronidase and tyrosinase in children diagnosed with acute lymphoblastic leukemia. Antioxidant and anti-melanoma activities were also examined and correlated with metabolomic data. For the first time, we discovered that the ethyl acetate fraction significantly inhibits hyaluronidase activity, with mean group values of 55.82% and 63.8% for aescin used as a control. However, interestingly, the fraction showed no activity against human tyrosinase, and in A375 melanoma cells treated with a doxorubicin fraction, doxorubicin activity decreased. This fraction exhibited the most potent antioxidant activity, which can be attributed to high contents of polyphenols, especially caffeic acid (24 mg/g). The findings suggest an important role of the ethyl acetate fraction in hyaluronidase inhibition, which may additionally indicate its anti-inflammatory property. The results suggest that this fraction can be used in inflammatory-related diseases, although with precautions in cases of patients undergoing chemotherapy.
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Acetatos , Antioxidantes , Eleutherococcus , Hialuronoglucosaminidase , Melanoma , Monofenol Mono-Oxigenase , Extratos Vegetais , Raízes de Plantas , Hialuronoglucosaminidase/antagonistas & inibidores , Hialuronoglucosaminidase/metabolismo , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/metabolismo , Humanos , Antioxidantes/farmacologia , Antioxidantes/química , Raízes de Plantas/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Melanoma/tratamento farmacológico , Melanoma/metabolismo , Acetatos/química , Eleutherococcus/química , Linhagem Celular Tumoral , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/químicaRESUMO
BACKGROUND: The region of the tricuspid valve is an important area for various cardiac interventions. In particular, the spatial relationships between the right coronary artery and the annulus of the tricuspid valve should be considered during surgical interventions. The aim of this study was to provide an accurate description of the clinical anatomy and topography of this region. METHODS: We analyzed 107 computed tomography scans (44% female, age 62.1 ± 9.4 years) of the tricuspid valve region. The circumference of the free wall of the tricuspid valve annulus was divided into 13 annular points and measurements were taken at each point. The prevalence of danger zones (distance between artery and annulus less than 2 mm) was also investigated. RESULTS: Danger zones were found in 20.56% of the cases studied. The highest prevalence of danger zones and the smallest distances were found at the annular points of the tricuspid valve located at the posterior insertion of the leaflets, without observed sex-specific differences. CONCLUSION: The highest risk of iatrogenic damage to the right coronary artery is in the posterior part of the tricuspid valve annulus.
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BACKGROUND AND AIMS: In recent years, there has been a growing interest in factor XIII in ischaemic stroke. The study's main aim was to assess the usefulness of factor XIII concentration determination in patients with acute ischaemic stroke (AIS) treated with thrombolysis with recombinant tissue plasminogen activator (t-PA). METHODS: The study was conducted in two groups of 84 patients with AIS: group I-with thrombolytic therapy and group II-without thrombolysis. A physical examination, neurological status (using the National Institutes of Health Stroke Scale, NIHSS), daily patients' activities measured with the Barthel Index and Modified Rankin Scale (mRS), and blood parameters were conducted on day 1 and day 7. The following parameters were assessed: highly sensitive C-reaction protein (CRP), fibrinogen, D-dimers (DD), neutrophil-lymphocyte ratio (NLR index), and the concentration of factor XIII-A. RESULTS: In group I, the concentration of XIII-A decreased significantly between day 1 and 7 (p < 0.001). In group I, the concentration of XIII-A on day 7 in Total Anterior Circulation Infarct (TACI) was significantly lower than in non-TACI stroke. XIII-A concentration in group I was significantly lower in patients < 31 points with Acute Stroke Registry and Analysis of Lausanne (ASTRAL). A greater decrease in XIII-A between the first sampling on day 1 and the second sampling on day 7 was associated with a worse patient neurological state in group I. CONCLUSIONS: In patients with AIS treated with t-PA, factor XIII concentrations decrease in the acute phase of stroke, and the largest decrease occurs in the TACI stroke. Determination of factor XIII concentration in patients with AIS can be used in clinical practice as an additional parameter supporting the assessment of stroke severity and may play a role in the prognosis; lower factor XIII-A activity may be a predictor of a worse prognosis.
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Fruits are very important dietary components and a source of biologically active compounds used in nutritional pharmacology. Particularly due to the presence of polyphenolic compounds, fruits play an important role in the prevention of diseases of civilization. Therefore, it is important to study the phytochemicals and biological activity of fruits, especially those with a long-standing use in ethnomedicine. In this study, we determined the chemical profile and biological activity of a methanolic extract of the Eleutherococcus divaricatus fruits. Amongst nine polyphenols studied, only chlorogenic acid, protocatechuic acid, and eleutheroside E have been detected. The extract showed a weak anti-hyaluronidase activity from bovine testicular in a range of 9.06-37.70% and quite high for human serum hyaluronidase from children diagnosed with acute leukemia in a range of 76-86%. A weak anti-tyrosinase activity was obtained in a range of 2.94-12.46%. Moreover, the extract showed antioxidant properties against DPPH radical, ABTS radical, and O2â¢-. In addition, the antioxidant activity of the extract was evaluated by FRAP assay and Fe2+ ion chelation assay. These preliminary studies partially justify the traditional use of the plant in inflammatory- and immune-related diseases, in which hyaluronidase and free radicals can participate. A difference in human serum hyaluronidase inhibition may result from the inter-patient variability. Regardless of that, the results mean that polyphenolic compounds may stimulate activity of hyaluronidase, as well as to protect cells from the oxidative damages. However, further studies in ex vivo and in vivo models are needed, including blood isolated from a larger number of patients.
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Antioxidantes , Eleutherococcus , Criança , Humanos , Animais , Bovinos , Antioxidantes/química , Frutas/química , Eleutherococcus/química , Hialuronoglucosaminidase , Extratos Vegetais/química , SoroRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Eleutherococcus senticosus (Rupr. et Maxim.) Maxim. has been used in traditional Russian medicine due to its recognized immunostimulant and anti-inflammatory activities. Compounds present in the fruits have demonstrated the capability to modulate the activity of enzymes such as hyaluronidase, suggesting their potential value in the development of effective therapies for various conditions where anti-inflammatory properties are beneficial, such as gastrointestinal diseases and tumor growth. AIM OF THE STUDY: In order to support the use of the fruits in folk medicine, this study is aimed to evaluate, post-mortem, the impact of E. senticosus fruits intractum (40 % extract made from fresh fruits) on the transepithelial electrogenic transport of sodium ions in the colon. The objective of this study was also to examine the impact of the intractum on proinflammatory serum hyaluronidase in children diagnosed with acute leukemia. METHODS: The study employed the Ussing technique to examine electrophysiological characteristics of isolated epithelial tissue, using the distal colon wall isolated from 10 New Zealand white male rabbits. The effect of the intractum on the inhibition of human serum hyaluronidase was examined with turbidimetric screening methods, using the blood samples collected from patients diagnosed with acute leukemia. RESULTS: For the first time, we discovered that the intractum used in the stimulation fluid, caused hyperpolarization reactions in colon tissue. Statistical analysis showed that these reactions were significantly different in relation to the control. The intractum significantly inhibited hyaluronidase activity with the mean value by group of 60 %, and 40 % for aescin used as a control. CONCLUSION: The results support the traditional use of the fruits in inflammatory-related diseases. The use of intractum of E. senticosus on the distal colon wall demonstrates its protective effect on the wall integrity and in a relation to hyaluronidase inhibition may additionally indicate its anti-inflammatory property. Thus, the results mean that the intractum may be used in colon-related diseases.
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Eleutherococcus , Leucemia , Criança , Humanos , Masculino , Coelhos , Animais , Extratos Vegetais/uso terapêutico , Frutas/química , Hialuronoglucosaminidase , Intestino Grosso , Leucemia/tratamento farmacológico , Anti-Inflamatórios/farmacologiaRESUMO
Iron overload emerges as a serious complication in myelodysplastic syndromes (MDS), particularly associated with frequent transfusions during the course of the disease. The discovery and description of hepcidin's mechanisms of action have contributed to a deeper understanding of iron metabolism. The existing literature reports a potential role of hepcidin in MDS, yet these data are fragmented and presented in an unstructured, somewhat chaotic manner. Hence, to address the existing data, we performed a systematic review of observational studies examining hepcidin levels in MDS. An extensive review of three bibliographic databases (Pubmed, Web of Science, and Scopus) enabled us to identify 12 observational studies. These studies focused primarily on adult patients with low-risk MDS who underwent transfusions and chelation therapy. An in-depth analysis of these manuscripts led to four main conclusions: (1) although high serum hepcidin levels are associated with MDS, most studies generally have not found a significant difference in these levels between patients and healthy individuals; (2) serum hepcidin levels are specific to MDS type; (3) serum hepcidin levels in MDS are strongly associated with transfusions and the genetic status of patients; and (4) high-risk MDS is associated with high serum hepcidin levels. While we have furnished a comprehensive summary of the significance of hepcidin in MDS, there are still gaps that future research should address. This pertains primarily to the capacity of hepcidin in predicting adverse outcomes for MDS patients and evaluating the efficacy of chelation therapy or the need for transfusion.
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Statins, which are inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, are an effective pharmacological tool for lowering blood cholesterol levels. This property makes statins one of the most popular drugs used primarily to prevent cardiovascular diseases, where hyperlipidemia is a significant risk factor that increases mortality. Nevertheless, studies conducted mainly in the last decade have shown that statins might prevent and treat liver cancer, one of the leading causes of cancer-related mortality worldwide. This narrative review summarizes the scientific achievements to date regarding the role of statins in liver tumors. Molecular biology tools have revealed that cell growth and proliferation can be inhibited by statins, which further inhibit angiogenesis. Clinical studies, supported by meta-analysis, confirm that statins are highly effective in preventing and treating hepatocellular carcinoma and cholangiocarcinoma. However, this effect may depend on the statin's type and dose, and more clinical trials are required to evaluate clinical effects. Moreover, their potential hepatotoxicity is a significant caveat for using statins in clinical practice. Nevertheless, this group of drugs, initially developed to prevent cardiovascular diseases, is now a key candidate in hepato-oncology patient management. The description of new drug-statin-like structures, e.g., with low toxicity to liver cells, may bring another clinically significant improvement to current cancer therapies.
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Despite the fact that there are many studies related to the adaptogenic and pro-healthy activities of plant-based compounds, there are some adaptogenic plants whose activities are not fully known, especially those coming from the wild regions of Asia, Africa, and South America. The aim of these studies was to examine the contents of non-nutritional compounds, such as polyphenols, flavonoids, and phenolic acids in ten adaptogenic species (Astragalus membranaceus (AM), Uncaria rhynchophylla (UR), Polygonum multiflorum (PM), Angelica sinensis (AS), Andrographis paniculatea (AP), Tinospora cordifolia (TC), Uncaria tomentosa (UT), Pfaffia paniculate (PP), Sutherlandia frutescens (SF), and Rhaponticum carthamoides (RC)). Considering biological activity, their antioxidant (DPPH, ABTS, FRAP, and ferrous-ion-chelating ability assays), anti-acetylcholinesterase, anti-hyaluronidase, and anti-tyrosinase activities were evaluated. The richest in polyphenols, flavonoids, and phenolic acids was UR (327.78 mg GAE/g, 230.13 mg QE/g, and 81.03 mg CA/g, respectively). The highest inhibitions of acetylcholinesterase, hyaluronidase, and tyrosinase were observed for TC, UR, and PM, respectively. In the case of antioxidant properties, extract from PM appeared to most strongly reduce DPPH, extract from UR inhibited ABTS, and extract from SF showed the best chelating properties. It should be noted that a particularly interesting plant was Ulcaria rhynchophylla. The results mean that there were compounds in UR with broad biological activities, and this species should be explored in more detail. Additionally, our results justify the traditional use of these species in the nutripharmacological or ethnopharmacological care systems of different regions.
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Antioxidantes , Fenóis , Antioxidantes/farmacologia , Polifenóis/farmacologia , África , Ásia , América do Sul , Flavonoides , AcetilcolinesteraseRESUMO
The pericardial sinuses are an important anatomical feature of the pericardial cavity, however, their clinical anatomy has not been thoroughly studied. In this study, we aim to provide the first classification of the oblique and transverse sinuses. We analyzed 121 computer tomography scans (46.3% female, age of 66 ± 12 years) of the pericardial cavity. The oblique sinuses were classified into four types: 1 (shallow with narrow entrance), 2 (shallow with wide entrance), 3 (deep with narrow entrance), and 4 (deep with wide entrance). The transverse sinuses were classified into four types: Concave, Wine-type, Straight, and Convex. The most common oblique sinus type was Type 1. The median oblique sinus volume was 8.4 (5.3) mL, the median entrance length was 33.0 (13.2) mm, and the depth was 38.2 (11.8) mm. The most common transverse sinus type was Concave. The median transverse sinus volume was 14.8 (6.5) mL, and the median length was 52.8 (17.7) mm. Our study provides an anatomical classification of the pericardial sinuses. The individual variability of the sinuses' morphology highlights the importance of understanding the clinical topography of the sinuses, particularly for minimally invasive thoracic ablation procedures.
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Factor VII activating protease (FSAP) was first isolated from human plasma less than 30 years ago. Since then, many research groups have described the biological properties of this protease and its role in hemostasis and other processes in humans and other animals. With the progress of knowledge about the structure of FSAP, several of its relationships with other proteins or chemical compounds that may modulate its activity have been explained. These mutual axes are described in the present narrative review. The first part of our series of manuscripts on FSAP describes the structure of this protein and the processes leading to the enhancement and inhibition of its activities. The following parts, II and III, concern the role of FSAP in hemostasis and in the pathophysiology of human diseases, with particular emphasis on cardiovascular diseases.
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Doenças Cardiovasculares , Fator VII , Animais , Humanos , Fator VII/metabolismo , Serina Endopeptidases/metabolismo , Peptídeo Hidrolases , Hemostasia/fisiologiaRESUMO
OBJECTIVE: Iron overload (IO) is a common and life-threatening complication resulting from the therapy of AL and HCT patients. This study aimed to evaluate the prognostic value of 12 serum biomarkers of iron metabolism in pediatric patients treated for AL or undergoing HCT. PATIENTS: Overall, 50 patients with AL after intensive treatment and 32 patients after HCT were prospectively included in the study. AL patients at diagnosis and healthy controls served as reference groups. METHODS: The impact of the following 12 serum iron metabolism parameters on the outcome of AL/HCT patients was analyzed: iron, transferrin (Tf), total iron-binding capacity (TIBC), ferritin, ferritin heavy chains (FTH1), ferritin light chains (FTL), hepcidin, soluble hemojuvelin (sHJV), soluble ferroportin-1 (sFPN1), erythroferrone (ERFE), erythropoietin (EPO), and soluble transferrin receptor (sTfR). RESULTS: With a median follow-up of 2.2 years, high levels of ferritin and low levels of sHJV had an adverse prognostic impact on OS and EFS in children after HCT. If these patients were combined with those with AL after intensive chemotherapy, the results were confirmed for OS and EFS both for ferritin and sHJV. CONCLUSIONS: Among the 12 analyzed serum parameters of iron metabolism, increased levels of ferritin and decreased levels of sHJV had an adverse prognostic impact on survival in children after HCT. More data are needed to clarify the relationship between ferritin, sHJV, and mortality of AL children after intensive chemotherapy, and more extensive prospective studies are required to prove sHJV predictivity.
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BACKGROUND: In March 2020, COVID-19 was announced as a global pandemic. The first COVID-19 patient was connected to an ECMO device in Israel during that time. Since then, over 200 patients have required ECMO support due to COVID-19 infection. The present study is a multi-institutional analysis of all COVID-19 patients requiring veno-venous (VV) ECMO in Israel. The aim was to characterize and compare the survivors and deceased patients as well as establish risk factors for mortality. METHODS: This retrospective multi-institutional study was conducted from March 2020 to March 2021 in eleven of twelve ECMO centers operating in Israel. All COVID-19 patients on VV ECMO support were included in the cohort. The patients were analyzed based on their comorbidities, procedural data, adverse event on ECMO, and outcomes. Univariate and multivariate analyses were used to compare the deceased and the surviving patients. RESULTS: The study included 197 patients, of which 150 (76%) were males, and the mean age was 50.7 ± 12 years. Overall mortality was 106 (54%). Compared with the deceased subjects, survivors were significantly younger (48 ± 11 vs. 53 ± 12 years), suffered less from ischemic heart disease (IHD) (3% vs. 12%), and were ventilated for a significantly shorter period (≤4 days) prior to cannulation (77% vs. 63%). Patients in the deceased group experienced more kidney failure and sepsis. Rates of other complications were comparable between groups. CONCLUSIONS: Based on this study, we conclude that early cannulation (≤4 days) of younger patients (≤55 years) may improve overall survival and that a history of IHD might indicate a reduced prognosis.
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Left atrial appendage occlusion affects systemic coagulation parameters, leading to additional patient-related benefits. The aim of this study was to investigate the differences in coagulation factor changes 6 months after epicardial left atrial appendage occlusion in patients with different LAA morphometries. This is the first study to analyze these relationships in detail. A prospective study of 22 consecutive patients was performed. Plasminogen, fibrinogen, tPA concentration, PAI-1, TAFI and computed tomography angiograms were performed. Patients were divided into subgroups based on left atrial appendage body and orifice diameter enlargement. The results of blood tests at baseline and six-month follow-up were compared. In a population with normal LAA body size and normal orifice diameter size, a significant decrease in analyzed clotting factors was observed between baseline and follow-up for all parameters except plasminogen. A significant decrease between baseline and follow-up was observed with enlarged LAA body size in all parameters except TAFI, in which it was insignificant and plasminogen, in which a significant increase was observed. Occlusion of the left atrial appendage is beneficial for systemic coagulation. Patients with a small LAA may benefit more from LAA closure in terms of stabilizing their coagulation factors associated with potential thromboembolic events in the future.
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OBJECTIVES: The association between hepcidin and acute leukemia (AL) or hematopoietic cell transplantation (HCT) in children and adults remains obscure. We aimed to assess this potential relationship through a systematic review of observational studies. METHODS: An electronic search of three databases, including PubMed, Scopus, and Web of Science Core Collection, was performed up to 31 March 2022. Two independent reviewers assessed the search results according to predetermined inclusion and exclusion criteria, following PRISMA guidelines. RESULTS: Of the 3607 titles identified, 13 studies published between 2008 and 2021 met the inclusion criteria. Most studies included a moderate number of participants and controls and used enzyme-linked immunosorbent assay (ELISA) to determine serum hepcidin levels. The principal findings: (1) serum hepcidin levels in patients with AL or undergoing HCT are increased compared to controls, regardless of the patient's age and the phase of disease treatment; (2) AL therapy and HCT significantly influence serum hepcidin levels; (3) serum hepcidin may predict a worse outcome in patients with AL and post-HCT. CONCLUSIONS: This systematic review provides an overview of observational studies that deal with the association of hepcidin with AL and HCT. Although disturbances in iron metabolism are common in AL and HCT, and hepcidin seems to play a cardinal role in their modulation, more extensive research is needed.
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In recent years, tremendous progress has been made in understanding the roles of extracellular vesicles (EVs) in cancer. Thanks to advancements in molecular biology, it has been found that the fraction of EVs called exosomes or small EVs (sEVs) modulates the sensitivity of cancer cells to chemotherapeutic agents by delivering molecularly active non-coding RNAs (ncRNAs). An in-depth analysis shows that two main molecular mechanisms are involved in exosomal modified chemoresistance: (1) translational repression of anti-oncogenes by exosomal microRNAs (miRs) and (2) lack of translational repression of oncogenes by sponging of miRs through long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs). At the cellular level, these processes increase the proliferation and survival of cancer cells and improve their ability to metastasize and resist apoptosis. In addition, studies in animal models have shown enhancing tumor size under the influence of exosomal ncRNAs. Ultimately, exosomal ncRNAs are responsible for clinically significant chemotherapy failures in patients with different types of cancer. Preliminary data have also revealed that exosomal ncRNAs can overcome chemotherapeutic agent resistance, but the results are thoroughly fragmented. This review presents how exosomes modulate the response of cancer cells to chemotherapeutic agents. Understanding how exosomes interfere with chemoresistance may become a milestone in developing new therapeutic options, but more data are still required.
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Antineoplásicos , Vesículas Extracelulares , MicroRNAs , Neoplasias , RNA Longo não Codificante , Animais , Antineoplásicos/uso terapêutico , Vesículas Extracelulares/patologia , MicroRNAs/genética , MicroRNAs/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , RNA Circular , RNA Longo não Codificante/uso terapêutico , RNA não TraduzidoRESUMO
The worsening of neurological status that occurs early after acute ischemic stroke (AIS) remains a serious issue, and the inflammatory response plays a key role in stroke pathobiology. Recently, endovascular treatment (EVT) has revolutionized the management and outcome of patients with AIS due to either extracranial carotid disease or intracranial disease. The neutrophil-to-lymphocyte ratio (NLR) represents an easily available inflammatory biomarker. The aim of the study was to assess the relationship between the NLR at admission and the occurrence of early neurological deterioration (END) in patients with AIS who underwent EVT. Patients with AIS and proximal arterial occlusion in the anterior circulation undergoing EVT were retrospectively identified. Absolute neutrophil count (ANC) and absolute lymphocyte count (ALC) were collected from admission blood work to calculate the NLR. The study outcome was END defined as an increase in at least 4 points in NIHSS score or death between baseline and 24 h after the ischemic event. Patients included were 211, and END occurred in 30 (14.2%). Patients with older age (OR = 1.07, 95% CI: 1.02−1.13), higher serum glucose (OR = 1.01, 95% CI: 1.01−1.02), and higher NLR (OR = 1.011, 95% CI: 1.04−1.18) had an increased risk of END. The best predictive cut-off value of NLR was 6.4, and END occurred in 24.1% and 3.9% of the patients with NLR ≥ 6.4 and <6.4, respectively (p < 0.001). In patients with AIS undergoing EVT, higher NLR values predicted a higher risk of END. Biomarkers able to identify inflammatory mechanisms might identify novel treatment targets and enhance proof-of-concept trials of immunomodulation in stroke.