Cardiovascular & Haematological Disorders - Drug Targets - Volume 22, Issue 2, 2022

A turbulent coagulation system is a prominent feature of Coronavirus Disease 2019 (COVID-19), with venous thromboembolism (VTE) a leading cause of death. Our hypothesis is that patients with inherited hypocoagulability, like congenital bleeding disorders (CBD), enjoy a protective effect against COVID-19-induced hypercoagulability and related fatal consequences. Our primary and follow-up observations revealed this effect, at least among patients with moderate to severe congenital bleeding disorders, particularly coagulation factor deficiencies. Theoretically, patients with inherited hypocoagulobility have only a potential protective effect against COVID-19-related hypercoagulability. Yet the lower rate of morbidity and mortality in patients with CBDs suggests that hypercoagulability and thrombotic events are the main cause of death in COVID-19. Therefore, appropriate and timely administration of anticoagulants could significantly decrease the rate of morbidity and mortality in COVID-19.

Background: Heart failure is the leading cause of morbidity and mortality worldwide. With improved longevity, the incidence and prevalence of heart failure continue to rise with an estimated prevalence of around 26 million worldwide. Heart failure with preserved ejection fraction (HFpEF) constitutes around 50% of the total heart failure cases and is the most common cause of heart failure in the elderly population. The cost of heart failure care continues to rise with care for heart failure hospitalization taking the major bulk. The cost was around 30 billion in the US in 2012 and is projected to reach 70 billion by 2030. Objective: This study aims to provide updated pharmacotherapy of heart failure with a preserved ejection fraction (HFpEF). Methods: We performed a comprehensive literature review to examine the available pharmacotherapeutics in the management of heart failure with a preserved ejection fraction using online databases (PubMed and Embase). Results: We reviewed multiple studies examining pharmacotherapeutics in the management of HFpEF and reducing heart failure hospitalizations in this cohort. Until recently, our management mainly focused on aggressively managing diabetes, hypertension, atrial fibrillation, and coronary artery disease anticipating improving the outcome. Beta-blockers, Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, sildenafil, digoxin, vericiguat, praliciguat, and Ivabradine did not improve heart failure hospitalization in this cohort. Conclusion: EMPEROR-PRESERVED (Empagliflozin) and PRESERVED-HF (Dapagliflozin) results in the management of HFpEF look promising irrespective of diabetes status. Sacubitrilvalsartan and Empagliflozon are the only medications approved for its management as per the PARAGON-HF and EMPEROR-PRESERVED studies, respectively.

Post-transplant lymphoproliferative disorders (PTLDs) are characterized by hyperproliferation of B cells due to solid organ or allogeneic hematopoietic stem cell transplant. Based on histological findings, it is divided into 4 categories. Most PTLD patients are Epstein–Barr virus (EBV) positive. Additionally, aggressive immunosuppressive therapies can also lead to PTLD. Reducing immunosuppressive regimes, antivirals, monoclonal antibodies, chemotherapy, and radiotherapy are available therapeutic options, depending on the nature and phase of the disease. This review briefly highlights pathogenesis, risk factors, prevention, and therapeutic strategies regarding PTLDs.

Background: Hypertension and heart failure are known risk factors for coronavirus disease 2019 (COVID-19) severity and mortality outcomes. Beta-blocker is one of the drugs of choice to treat these conditions. The purpose of this study is to explore the relationship between preadmission beta-blocker use and COVID-19 outcomes. Methods: PubMed and Europe PMC were used as the database for our search strategy by using combined keywords related to our aims until December 10th, 2020. All articles related to COVID- 19 and beta-blocker were retrieved. Review Manager 5.4 and Comprehensive Meta-Analysis 3 software were used to perform statistical analysis. Results: A total of 43 studies consisting of 11,388,556 patients were included in our analysis. Our meta-analysis showed that the use of beta-blocker was associated with increased risk of COVID-19 [OR 1.32 (95% CI 1.02 - 1.70), p = 0.03, I² = 99%, random-effect modelling], clinical progression [OR 1.37 (95% CI 1.01 - 1.88), p = 0.04, I² = 89%, random-effect modelling], and mortality from COVID-19 [OR 1.64 (95% CI 1.22 - 2.19), p = 0.0009, I² = 94%, random-effect modelling]. Metaregression showed that the association with mortality outcome were influenced by age (p = 0.018) and hypertension (p = 0.005). Conclusion: The risk and benefits of using beta-blocker as a drug of choice to treat hypertensive patients should be considered and reviewed individually, case by case, knowing their association with higher incidence and severity of COVID-19 infections. Other first-line antihypertensive drugs may be considered as an alternative therapy if the risk of administering beta blockers outweighs the benefits of COVID-19 infection. Registration details: PROSPERO (CRD42021260455).

Aims: The study aimed to assess the antidiabetic effect of Salvia tingitana (S. tingitana). Background: S. tingitana is an aromatic plant that belongs to the Lamiaceae family. Phytochemical analysis of the aerial parts of S. tingitana revealed the existence of terpenoids and flavonoids. In addition, S. tingitana possesses antimicrobial activity. Objective: The goal of the study was to obtain information about the antihyperglycemic, antihyperlipidemic, antioxidant abilities of S. tingitana aqueous extract. Methods: The effect of an acute and sub-chronic administration of S. tingitana aqueous extract (AEST) at the doses of 60 and 80 mg/kg on glucose, lipid profile, and lipoprotein profile was examined in normoglycemic and hyperglycemic rats. Additionally, a preliminary phytochemical screening and the antioxidant activity using DPPH assay were carried out. Results: Rats treated with AEST at a dose of 60 mg/kg showed a significant decrease in the serum glucose levels during the single oral administration at the 4th and 6th hour of treatment in both normal and streptozotocin(STZ)-induced hyperglycemic rats. Interestingly, a dose of 80 mg/kg AEST produced a significant lowering effect on blood glucose levels at the 2nd, 4th, and 6th hour of treatment after a single oral administration in both diabetic and normal rats. Both doses of AEST (60 and 80 mg/kg) revealed a significant amelioration of lipid and lipoprotein profile. In addition, the qualitative and quantitative phytochemical analysis proved the presence of polyphenols compounds, flavonoids, and tannins. Results suggest that S. tingitana contains some secondary metabolites like alkaloids, phenols, flavonoids, and saponins. Importantly, the study revealed that the aqueous extract of S. tingitana has a very interesting antioxidant activity (IC50 = 553.21 μg/ml). Conclusion: The study illustrates the beneficial action of the aqueous extract of S. tingitana as an antihyperglycemic and antihyperlipidemic agent.

Background: Reactivation of HbF is a potential strategy to ameliorate symptoms of hemoglobinopathies such as sickle cell disease and b-thalassemia. After birth, there is a switch from fetal to adult hemoglobin, for which the molecular mechanisms and key regulators await further understanding in order to develop effective methods for HbF reactivation. Bcl11a, one of the major HbF reactivation regulators, demonstrates no significant changes at transcriptional levels in F erythroblasts compared to the non-HbF expressing cells. Therefore, it is possible that posttranscriptional regulation and epigenetic effects, for which the miRNAs play an important role, are the primary causes of the decreased Bcl11a protein level in adult erythroblasts. Objective: This paper aims to determine the differentially expressed mRNAs and miRNAs of erythroblasts in HSCs from the fetal liver and bone marrow. Methods: Raw high-throughput sequencing data (GSE110936, GSE90878) was downloaded from Gene Expression Omnibus (GEO) database. After RNAseq analysis, several data sets and tools were used to select key genes and examine selection validation. Results: We selected 42 DEmRNAs and nine DEmiRs, including hsa-let-7f-5p, hsa-miR-21-5p, hsamiR- 22-3p, hsa-miR-126-5p, hsa-miR-146b-5p, hsa-miR-181a-5p, hsa-miR-92a-3p, hsa-miR-25-3p and hsa-miR-191-5p. Furthermore, hub genes including hist1h2bl, al133243.2, trim58, abcc13, bpgm, and fam210b were identified in the coexpression network, as well as RPS27A in the PPI network. Functional analysis revealed that these DEmRNAs and DEmiRs might play a role in gene expression regulation at multiple levels. Gene set enrichment analysis, in particular, revealed a possible role for genes in the globin switching process. Conclusion: According to our findings, a number of the DEmRNAs and DEmiRs may play significant roles in globin switching regulation and thus have the potential to be applied for HbF reactivation.