Cardiovascular & hematological disorders drug targets最新文献

Objectives: This study aims to investigate the mechanisms underlying the role of chromatin regulator-related genes (CRRGs) in coronary artery disease (CAD) and develop a diagnostic model for CAD.

Methods: We downloaded CAD datasets from the GEO database and utilized R software for machine learning, modeling, and classification of CAD based on CRRGs.

Results: The random forest model was found to be the best approach, identifying USP44, MOCS1, SSRP1, ZNF516, and SCML1 as the top contributing genes for CAD diagnosis and prevention. Differentially expressed CRRGs were associated with aberrant immune cell infiltration in CAD patients. CAD patients were classified into two subtypes based on the expression of differentially expressed CRRGs. The differential expression analysis identified MMP9, LCE1D, LOC92659, SYNGR4, EN2, CACNA1E, GPR78, and LOC92249 as differentially expressed genes distinguishing the two subtypes of CAD. Functional analyses revealed that the differentially expressed genes are enriched in biological processes related to cellular functions, such as responses to metal ions and inorganic substances. The enriched pathways included inflammation and hormone-related pathways, such as IL-17 signaling, endocrine resistance, TNF signaling, and estrogen signaling pathways.

Conclusion: CAD is associated with CRRGs, which may represent a new direction for CAD treatment.

Background: Gestational hypertension (GH) and preeclampsia (PE) are two important complications of pregnancy. Considering the U-shaped association between thyroidstimulating hormone (TSH) and hypertensive disorders of pregnancy in some reports, we decided to investigate the effect of levothyroxine treatment on GH and PE in pregnant women with subclinical hypothyroidism (SCH) overt hypothyroidism (OH), and autoimmune thyroid diseases.

Methods: Google Scholar and databases, such as ProQuest, Medline, Cochrane Library, ScienceDirect, and Scopus were searched electronically for clinical trials and observational studies using the following search terms: (("levothyroxine" OR "LT4" OR "thyroxine supplementation") AND ("subclinical hypothyroidism" OR "SCH" OR "thyroid peroxidase antibodies" OR "autoimmune thyroid disease") AND ("pregnancy outcomes" OR "preeclampsia" OR "gestational hypertension" OR "PIH")). Further, we investigated the impact of levothyroxine on the incidence of GH and/or PE compared with control or placebo groups from April 4 to November 1, 2022.

Results: After treatment with levothyroxine, the odd ratios (ORs) of GH and PE in subclinical [OR = 1.03, 95% CI: (0.85, 1.25), I² = 35.25%, P =0.78, OR = 1.02, 95% CI: (0.66,1.58), I² = 46.86%, P =0.94, respectively] and overt hypothyroidism [OR=1.10, 95% CI: (0.70,1.71), I²=38.44%, P =0.69, OR=1.32, 95% CI: (0.83, 2.09), I²=0.00%, P =0.24, respectively] were not different from controls. Furthermore, this result was observed in studies that recruited women with SCH and OH [OR=1.12, 95% CI: (0.58, 2.14), I²=92.74%, P =0.74, OR=0.51, 95% CI: (0.15, 1.72), I²=97.30%, P =0.28, respectively]. Additionally, the odds ratios of GH and PE were statistically similar in women who were TPOAb-positive compared to those who were TPOAbnegative (OR=1.01,95% CI: (0.80, 1.28), (I² =0.00%, P =0.00). However, LT4 reduced the risk of GH in treated TPOAb+ women compared with untreated TPOAb+ (OR=0.43, 95% CI: (0.30, 0.62), I²=0.00%, P =0.00).

Conclusion: Following LT4 therapy, the incidence rates of GH and PE in all forms of hypothyroidism showed no significant difference compared to the control group. However, the decrease in GH was noteworthy for TPOAb+ women using levothyroxine compared to those not using it.

Atherosclerosis and ischemic events play a pivotal role in the pathogenesis of several cardiovascular diseases (CVD). The primary aim of preventing recurrent thrombosis in patients who underwent cardiovascular surgery is the antiplatelet agent administration. Nevertheless, despite the aspirin therapy or double (aspirin plus clopidogrel) therapy, the effectiveness of antithrombotic treatment remains controversial. In recent years, we have learned that some percentage of patients still demonstrate no clinical response to aspirin treatment and may experience a vascular complication. This article provides an overview of recent scientific studies that have focused on experimental detection and genotyping of single nucleotide polymorphisms (SNPs) in patients, involving the main therapeutic target genes: cyclooxygenase COX-1 and COX-2, guanylate cyclase GUCY1A3, the glycoprotein complex GPIIb-IIIa, and the platelet receptor protein PEAR1." The aspirin resistance (AR) ranges considerably from 0 % to 66% in patients with ischemic heart disease (IHD) and relatively healthy people (control group). SNP distribution analysis has been proposed to explain the inadequate high platelet reactivity (HPR) among patients with IHD under aspirin treatment. Various SNPs have been proposed to explain the development of CVD and the persistent HPR under aspirin treatment widely used in the prevention of recurrent cardiovascular thrombotic events. Meanwhile, the efficacy of aspirin therapy in secondary thrombosis prevention in patients with IHD is not strongly associated with known SNP. The inconsistent results of different AR clinical trials are likely due to the design of the experiments and methodological and quantitative issues; therefore, careful interpretation of the SNP genotyping results is necessary.

Background: The consumption of coffee as a beverage and honey as a sweetener is prevalent worldwide, with each having potential health implications. However, studies on the combined effect of coffee and honey on blood pressure, heart rate, and blood glucose level are lacking.

Objectives: The objective of this study is to determine whether a three-day consumption of honey- sweetened coffee will significantly alter the systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR), and fasting blood glucose (BG) levels in young, healthy female adults.

Methods: Thirty participants studying at the University of Uyo, aged 18 to 26 years, were randomly assigned to three groups: control, coffee, and honey-sweetened coffee groups with 10 subjects each. The control group was given 250 mL of warm water, the coffee group was given 2.25 g of coffee dissolved in 250 mL of hot water, and the honey-sweetened coffee group was given 2.25 g of coffee with 20 mL of honey dissolved in 250 mL of hot water for three consecutive days. Before the start of the experiment, the subjects were asked to rest by sitting comfortably for 15 minutes. Baseline measurements of blood pressure, heart rate, and blood glucose were taken and recorded before the consumption of the assigned beverage. Follow-up measurements were taken at 15, 30, 45, and 60 minutes after consumption for blood pressure and heart rate and 30 and 60 minutes for blood glucose level. This procedure was repeated for three days.

Results: The results showed no significant changes in systolic blood pressure, diastolic blood pressure, mean arterial pressure, heart rate, and blood glucose level in the coffee and honey-sweetened coffee groups compared to the control group.

Conclusion: The findings of this study revealed that honey-sweetened coffee has no acute effect on blood pressure, heart rate, and blood glucose level in healthy female individuals. It can, therefore, be concluded that honey-sweetened coffee has a neutral effect on these physiological parameters, but a more elaborate study is highly recommended.

Background: Thromboembolism with solid malignancies is a commonly associated feature, which is less common in hematological malignancies. Disseminated intravascular coagulation (DIC) causing thrombotic events is characteristically associated with certain hematological malignancies (e.g., acute promyelocytic leukemia (APL). Acute myeloid leukemia (AML) presenting as extensive thromboembolism is not a common clinical presentation. Anticoagulation in these subsets of patients remains a major challenge since patients often have thrombocytopenia and bleeding manifestations, requiring close monitoring.

Case presentation: A 54-year-old male with a known case of ischemic heart disease on regular anti- platelet therapy presented with acute onset progressive shortness of breath with mild anemia. On further evaluation, the patient was diagnosed with bilateral pulmonary artery and venous thrombosis along with left complete renal and partial inferior vena cava (IVC) thrombosis. The patient was started safely on anticoagulant therapy with normal platelet counts. Later, peripheral smear and immunophenotyping by flow cytometry revealed the diagnosis of acute myeloid leukemia, and the patient started its treatment.

Conclusion: Extensive arterial and venous thrombosis at presentation of acute myeloid leukemia is an uncommon finding and needs anticoagulation therapy along with the treatment of the underlying disease. Close monitoring of bleeding and maintaining an adequate platelet count is required, especially in hematological malignancies.

Toll-like receptors (TLRs) belong to the innate immune system. TLRs identify and respond to invading pathogens by recognizing certain molecular patterns associated with the infections. TLRs are crucial for the host's defence against these diseases. TLRs are capable of detecting several endogenous chemicals through the recognition of damage-associated molecular patterns, which are generated in response to various harmful situations. Recent animal studies have shown that TLR signaling has a significant role in the development of serious heart diseases, such as ischemia myocardial damage, myocarditis, and septic cardiomyopathy, where inflammation of the heart muscle is a key factor. This manuscript examines the animal research findings on (1) TLRs, TLR ligands, and the signal transduction system, and (2) the significant involvement of TLR signaling in these crucial cardiac diseases.

Background: Inter-atrial septum (IAS) stenting in duct-dependent congenital heart disease patient has shown to be an effective way to maintain inter-atrial blood flow, however it is still considered a high risk procedure and inter-atrial septum stenting remains a low-frequency procedure.

Method: A single-center observational cohort study was carried out at the National Cardiovascular Center Harapan Kita (NCCHK) between April 2019 and April 2023. This study included duct-dependent congenital heart disease patients. The extracted data were baseline characteristics, clinical findings, complications, and outcomes of the patients.

Result: Eleven patients with duct-dependent physiology were intervened with inter-atrial septum stenting. The patients were 4 females and 7 males with the median age of implantation being 150 days (range 11-703 days) and the median weight being 3.9 (range 2.8-9) kg, with 2 patients weighing less than 3 kg. The average stent diameter was 8.50 (2.03) mm with an average length of 24.45 (7.94) mm. Non-restrictive atrial flow was successfully achieved in 90.90% of the procedures, corresponding to 10 patients.

Conclusion: Inter-atrial septum stenting in duct-dependent congenital heart disease patients produces reliable patency with a very good intra-procedural success rate.