Cardiovascular & hematological disorders drug targets最新文献

The past decade has appreciated personalized medicine as a novel medical approach that deals with all practices that are tailored to individual patients. Personalized treatment or personalized cardiology for cardiovascular disorders is an emerging medicine system for related patients. Personalized cardiology is solely based on genomics and proteomics; molecular diagnostics and biomarkers of the cardiovascular system link diagnosis with therapy. Bioinformatics is useful in CVD risk stratification and might improve risk-estimating algorithms. Personalized cardiology involves 3D printing, pharmacotherapy, surgery, lifestyle modifications, and combinations thereof. Understanding the pathology of CVD and identifying causative factors at the individual level can provide opportunities for developing personalized medicine. Since it offers novel avenues for diagnosing, preventing, and treating CVD, molecular genetics has made a substantial contribution to the field of molecular cardiology. Nonetheless, there are still a lot of obstacles to overcome from the standpoints of science and policy. These obstacles can be avoided using evidence-based procedures, clinical applications, biomarker-based detection techniques, comprehensive concepts, and understanding. Targeted therapies may be developed as a result of improved disease classification and a better knowledge of the individual differences in pathology. Cardiovascular disorders, like hypertension, angina, or ischemic heart, a condition of reduced blood flow to the heart, coronary artery disease or damaged blood vessels, myocardial infarction or resisted blood flow to the myocardium, and cardiac arrhythmia or irregular cardiac cycles are the primary targets for personalized cardiology. The current review discusses various parameters for personalizing the treatment of cardiovascular disorders.

Objective: 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: Casimiroa edulis La Llave (Rutaceae), commonly known as "zapote blanco", is a tree widely distributed in the tropical and subtropical areas of Mexico. The decoction of its leaves is traditionally used as a natural remedy to treat hypertension and anxiety.

Objective: The present study aimed to determine the vasorelaxant and antihypertensive effects of C. edulis extracts and evaluate the acute and sub-acute toxicity of one of the most active extracts.

Methods: The hydro-alcohol and organic (hexane, dichloromethane, and methanol) extracts, obtained from the leaves of C. edulis, were evaluated on isolated aorta rat rings in the presence and absence of endothelium to determine their vasorelaxant effect. Then, most active extracts were studied to evaluate the functional mechanism of their vasorelaxant action and antihypertensive effect on spontaneously hypertensive rats (SHR). The acute and sub-acute toxicity of dichloromethane extract was evaluated following the OECD 423 and 407 protocols.

Results: The hexane (HE) and dichloromethane (DE) extracts from Casimiroa edulis induced significant vasorelaxant action on isolated rat aortic rings with (Emax 104.7 ± 1.4% and Emax 97.3 ± 6.7%, respectively) and without (Emax 94.9 ± 3.5% and Emax 67.4 ± 1.0%, respectively) endothelium, and this effect was partially endothelium-dependent. Their vasorelaxant action was modified by L-NAME (nitric oxide synthase inhibitor) and ODQ (soluble guanylyl cyclase inhibitor); however, indomethacin did not modify the effect. Also, both HE and DE significantly decreased the contraction induced by KCl in a concentration-dependent manner and the maximal effect induced by CaCl2. Moreover, DE showed a significant decrease in systolic and diastolic blood pressure in SHR at 7 hours and 15 days after treatment, respectively. Finally, the toxicity test of DE allowed classifying it in category 5, indicating it to be a non-toxic extract based on OECD guideline 423; the LD50 value was estimated to be greater than 2,000 mg/Kg and smaller than 5,000 mg/Kg in Wistar rats.

Conclusion: The results demonstrated hexane and dichloromethane extracts to exert a vasorelaxant effect through endothelium-dependent NO release and cGMP increase, as well as by calcium channel blockade. Also, dichloromethane extract showed efficacy and security as a potential antihypertensive agent.

Background: Chronic myeloid leukemia [CML] is a common hematological malignancy where patients present with varied clinical symptoms and are usually diagnosed with incidentally detected elevated total leucocyte counts in hemogram. The presence of pelvic hematoma at the presentation of CML is an uncommon finding.

Case presentation: Two male young adults presented with massive splenomegaly and pelvic hematoma. On evaluation for anemia and leukocytosis with massive splenomegaly, diagnosis of CML chronic phase [CML-CP] was made on peripheral smear, bone marrow examination including cytogenetic study and molecular methods [peripheral blood quantitative BCR: ABL1 by real-- time PCR]. The first patient underwent aspiration of hematoma, and the second patient presented late where the hematoma organized into a solid mass and no intervention could be possible. A basic available coagulation study revealed no abnormalities and was managed with tyrosine kinase inhibitors.

Conclusion: Initial manifestation of CML with pelvic hematoma is uncommon and should undergo aspiration or drainage to avoid organization of hematoma and compressive symptoms locally.

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 (SGH), 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]. Also, these studies compared thyroperoxidase antibodies between TPOAb-positive participants with TPOAb-negative controls (OR=1.01, 95% CI: (0.80, 1.28), I² =0.00%, P =0.90). However, LT4 reduced the risk of GH in TPOAb+ women compared with untreated TPOAb+ (OR=0.43, 95% CI: (0.30, 0.62), I² =0.00%, P =0.00).

Conclusion: After LT4 therapy, the incidence rates of GH and PE in any form of hypothyroidism were not significantly different from controls. However, the reduction of GH in women with TPOAb+ who used levothyroxine needs further consideration.

Background: Pulmonary embolism (PE) is a frequent cause of death. Acute PE may be treated either with full anticoagulation (AC) alone or thrombolytic therapy with systemic tissue-- type-plasminogen-activator (tPA) based on risk assessment. Currently, AC is the standard of care for most patients with intermediate-high-risk PE, with low-dose tPA emerging as an effective alternative. However, studies directly comparing the efficacy and safety of low-dose tPA to AC are lacking in this patient population.

Objective: The aim of this study was to retrospectively compare the efficacy and safety of low-- dose tPA, compared to AC alone in right ventricular function and in-hospital mortality and bleeding complications in patients presenting with intermediate-high risk PE.

Methods: This is a single-center, retrospective cohort trial conducted at a university hospital. A total of 148 patients were screened, and 88 patients qualified for this study. The primary endpoints were changes in right ventricular function on echocardiogram in 24 hours, in-hospital mortality, and major bleeding complications.

Results: Eighty-eight consecutive patients with intermediate high-risk PE were included. Twenty- six patients (29.5%) received low-dose systemic tPA administered via intravenous infusion, and 62 patients (70.4%) received standard full-dose anticoagulation. There were no significant differences in baseline vital signs or PESI scores between the low-dose tPA and the AC group. Patients in the low-dose tPA group had worse RV function and higher troponin levels at baseline but showed significant improvement in all RV parameters assessed during the 24-hour follow-up. In comparison, there was no significant improvement in RV function in the AC group. There were more bleeding events in the AC group. LOS was shorter in the low-dose tPA group.

Conclusion: Treatment with low-dose prolonged infusion of tPA may be an effective and safe therapy in patients with intermediate-risk PE. Compared to AC, low-dose tPA was effective in decreasing PASP and restoration of RV function.

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.

Objective: 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.

Introduction: In-stent restenosis (ISR) is a recurrence of a blockage in a section of the coronary artery that has previously been treated with a stent. Molecular/biochemical pathways underlying ISR are not fully understood, but inflammation and reactive oxygen species (ROS) induced oxidative stress play a significant role in the pathogenesis of restenosis. As blood cells are highly sensitive to oxidative stress and blood is readily accessible compared to other tissues, the current study flow cytometrically investigated intracellular ROS and cytokine profile of blood cells as possible markers of restenosis. Flow cytometry is commonly used for detecting ROS and analyzing oxidative stress but so far, it has not been utilized for prediction of ISR. So, the aim of the study was to explore the potential of flow cytometric assessment of ROS levels in the blood cells as predictor of ISR.

Methods: The study was carried out in a total of 60 patients who had previously undergone coronary artery stent implantation. They were categorized as Group I - Coronary stent implanted patients without restenosis (n=30) and Group II - Coronary stent implanted patients with restenosis (n=30). Sociodemographics, biochemical and angiographic characteristics were assessed. Intracellular ROS and cytokine estimation in blood cells was done by using flow cytometric analysis.

Results: Flow cytometric measurements demonstrated a 1.3-fold increase in ROS levels in red blood cells (RBCs) and 2-fold increase in ROS levels in leucocytes in group II as compared to group I. Mean serum concentrations of pro-inflammatory cytokines: tumor necrosis factor-α (33.54 ± 6.48 vs. 20.10 ± 5.61, p <0.001***), interferon-gamma (21.76 ± 4.46 vs. 20.10 ± 5.61, p <0.001***), interleukin 6 (152.56 ± 30.67 vs. 113.95 ± 23.38, p <0.001***) were found to be higher in restenotic patients as compared to the non-restenotic patients. Correlation analysis showed that intracellular ROS levels of RBCs exhibited a significant positive correlation with late lumen loss in restenotic (r=0.71, p <0.01) as well as non-restenotic patients (r=0.59, p <0.01). Similarly, intracellular ROS levels of WBCs exhibited a significant positive correlation with late lumen loss in restenotic (r=0.72, p <0.01) as well as non-restenotic patients (r=0.61, p <0.01).

Conclusion: This study highlights the role of increased levels of intracellular ROS in blood cells in the subsequent development of ISR, which can be detected flow cytometrically. The study suggests that intracellular ROS estimation in blood cells may serve as a potential marker for restenosis and their flow cytometric analysis may facilitate the prediction of ISR.

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.