Cardiovascular and Hematological Disorders - Drug Targets最新文献

Aims: The aim of the study was to investigate the antihyperglycemic effect of L-Tartaric acid.

Background: L-Tartaric acid is a natural product with possible beneficial effects on health.

Objective: The goal of this work was to evaluate the antihyperglycemic and antidyslipidemic effects of L-Tartaric acid (L-TA) in rats.

Materials and methods: In the first model, the effects of L-TA (10 and 40 mg/kg) on diabetes conditions induced by streptozotocin (STZ) in rats were investigated. In the second model, the effects of L-TA (40 and 80 mg/kg) on dyslipidemia induced by tyloxapol (Triton WR-1339) in rats were assessed.

Results: L-TA (40 mg/kg) had improved all studied parameters. L-TA at 40 mg/kg was able to significantly reduce glycaemia, improve oral glucose tolerance (OGT), increase glycogen content in liver and extensor digitorum longus (EDL) muscle, and ameliorate the lipidic profile and atherogenic indices in STZ-diabetic rats.

Conclusion: L-Tartaric acid was able to exhibit antihyperglycemic and antidyslipidemic effects in STZ-induced diabetic rats. Moreover, the antidyslipidemic effect of L-Tartaric acid was confirmed in tyloxapol-induced hyperlipidemic rats.

Background: Plant and their active phytoproducts have been used in modern medicine and playing an important role in the health sectors since a very early age. Human beings need a considerable amount of these plant-based phytochemicals for their health. The flavonoidal class phytochemical is an important class of natural products in modern healthcare because of their different pharmacological activities and health benefits. Flavonoidal class phytochemicals have been used to treat diabetes and related secondary complications in humans. Flavonoids have antiapoptotic, anti-hyperlipidemic, anti-inflammatory, and anti-oxidant potential in the health sectors. Sinensetin, also called 3',4',5,6,7-pentametoksiflavon is a colorless compound with a molecular weight 372.37g/mol and is found to be present in the Orthosiphon stamineus.

Methods: In the present investigation, we aim to collect scientific information on sinensetin and analyze it for its biological potential and therapeutic benefits against various types of disorders and complications. Medicinal importance and pharmacological activities data have been collected and analyzed in the present work for sinensetin through literature data analysis of different research works. Google Science Direct, PubMed, Scopus, and Google Scholar were mainly searched to collect the scientific information in the present work. The present work analyzed sinensetin biological potential, pharmacological activities, and analytical aspects.

Results: Literature data analysis of different scientific research works revealed the biological potential of phytochemicals in medicine, including flavonoids. Sinensetin has anti-tumor, antiinflammatory, anti-oxidant, anti-diabetic, and antibacterial activities through their testing in different in vitro and in vivo models. Sinensetin has physiological functions, including anti-oxidant, antiinflammation, and anti-cancer potential in medicine. Scientific data analysis signified the biological importance of sinensetin against tumors, gastric cancer, colorectal cancer, breast cancer, diabetes, influenza H1N1 infection, obesity, inflammation, colitis, brain disorders, and microbial infections. Further biological potential of sinensetin on enzymes and angiogenesis has been analyzed in the present work. Sinensetin was isolated through different analytical and extraction techniques, including chromatographic techniques.

Conclusion: Literature data analysis signified sinensetin's biological potential and pharmacological activities in medicine.

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.

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.

Aims: The study aimed to evaluate the glucose-lowering effect of Tetraclinis articulata.

Background: Tetraclinis articulata is commonly used for the treatment of diabetes characterized by chronic hyperglycemia.

Objective: This work aimed to evaluate the effect of Tetraclinis articulata (T. articulata) Aqueous Extract (TAAE) on glycemia and lipid profile in normal and Streptozotocin (STZ)-induced diabetic rats. Additionally, its acute toxicity, phytochemical composition, and antioxidant capacity were assessed.

Methods: To highlight the effect of TAAE on plasma glucose levels and lipid metabolism, blood glucose levels were measured at 1, 2, 4, and 6 hours of treatment for the acute test and on days 2, 4 and 7 over the daily oral administration for the subchronic test at two selected doses (10 mg/kg and 20 mg/kg). Furthermore, Triglycerides (TGs), Total Cholesterol (TC), and High-Density Lipoprotein cholesterol (HDL-c) were measured after the treatment. The rats' liver, extensor digitorum longus (EDL), and soleus muscle were isolated from diabetic rats treated with TAAE at a dose of 20 mg/kg at the end of the experiment to measure glycogen content using a standard method. The acute toxicity of TAAE was examined according to the OECD guideline. In addition, body weight, signs of toxicity, and/or mortality were observed for 14 days. Besides, a preliminary phytochemical screening, quantification of phenolic, flavonoid, and tannin contents as well as the antioxidant activity, were evaluated.

Results: The results showed that TAAE at the doses of 10 and 20 mg/kg possesses a potent antihyperglycemic effect in STZ-treated diabetic rats and an acute hypoglycemic effect in normal rats, as well as the extract provoked a decrease of blood glucose levels after glucose loading in the glucose tolerance test in a dose-dependent manner. TAAE at a dose of 20 mg/kg revealed a significant improvement in the lipid profile. However, treatment with TAAE at a dose of 20 mg/kg did not significantly modify the glycogen content. In the same way, the acute toxicity analysis revealed no death or signs of toxicity in rats, and the LD50 value was more than 2 g/kg. In addition, preliminary phytochemical screening revealed that TAAE revealed the presence of polyphenols, flavonoids, tannins, carbohydrates, saponins, quinones, sterols and terpenoids. Furthermore, TAAE exhibited a potent antioxidant activity, which may be due to the richness in polyphenol content (756.21 ± 6.72 mg GAE/1 g of extract).

Conclusion: The current study demonstrates for the first time that aqueous Tetraclinis articulata extract has a potent glucose-lowering effect.

Background: The Primary Percutaneous Coronary Intervention (PPCI) is the preferred therapeutic strategy for patients who experienced ST-Elevation Myocardial Infarction (STEMI).

Objective: We aimed to evaluate the association of hematological indices, including hemoglobin level, platelets, White Blood Cells (WBCs) count, and MPV before PPCI with the TIMI grade flow after PPCI.

Methods: STEMI patients who experienced PPCI were included in the present retrospective crosssectional study. Then participants were divided into three groups based on their post-procedural TIMI flow grades. Demographic data and hematologic indices of patients before PPCI were collected and their association with the TIMI grade flow after PPCI was evaluated. To compare the quantitative and qualitative variables, chi-square and t-tests were performed, respectively.

Results: We found that elevated levels of hemoglobin and decreased levels of MPV had a significant association with an advanced grade of TIMI flow. Interestingly, in the normal range, there was a significant association between higher platelet count and TIMI-flow grade 1. Besides, TIMI flow grades 2 and 3 had a significant association with low and moderate platelets count, respectively.

Conclusion: In conclusion, evaluating MPV, platelets, and hemoglobin levels before PPCI as easy and accessible parameters may be able to identify high-risk STEMI patients undergoing PPCI.

Background: ST-elevation myocardial infarction (STEMI) is known to be associated with significant arrhythmia and consequent mortality. QT prolongation is a risk factor for arrhythmia in STEMI patients who underwent primary percutaneous coronary intervention (PPCI). The aim of this investigation was to evaluate the association of corrected QT interval (QTc), QT dispersion (QTd), T-wave peak to end (TPE), and fragmented QRS with mortality in these patients.

Methods: Eligible patients with the characteristic symptoms of STEMI who underwent PPCI were included. QTc, QTd, TPE, and fragmented QRS were measured before and after the PPCI. These predictors were compared between patients who died during hospitalization and discharged patients.

Results: After coronary angiography, 10 patients (4%) died during the hospitalization after PPCI. Comparing the non-survivers and discharged patients in terms of arrhythmia predictors showed that the mean QT dispersion and TPE before intervention were significantly higher in the non-survivors. Also, the number of patients who experienced fragmented QRS before and after the intervention was significantly higher in the non-survivors.

Conclusion: These data suggested that evaluating such arrhythmia predictors, especially before PPCI, could be used as a predictor of mortality in STEMI patients who underwent PPCI.

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.

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.

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