Background: Past few decades have witnessed the co-existence of diabetes and hypertension leading to other health disorders. Hence, it is imperative to look into new therapies for the treatment of both hypertension and diabetes simultaneously in order to gradually reduce the pill burden and subsequent side effects.
Objective: The goal of the current work was to use several in silico methods to develop new entities that have both anti-diabetic and anti-hypertensive activity.
Methods: Structure activity relationship was drawn from the literature considering Thiazolidinones (Anti diabetes), Indole (Antihypertensive) and naturally occurring polyphenols (Dual activity) for simultaneous management of hypertension and diabetes. Fifty-six new chemical entities were designed and subjected to ADME and docking studies. Based on the Lipinski filter, bioavailability and lead likeness nineteen molecules were further docked into three PDB's (5Y2T, 4BVN, 1O8A).
Results: The majority of the NCE's have shown higher binding affinities than the standard drugs, with Compound 42 having the best results. Among nineteen NCE's, 50% of the compounds have shown the involvement of Thiazolidinone, Indole and Catechol pharmacophores with prominent hydrogen bonds, hydrophobic, electrostatic and pi-pi stacking interactions with all three PDB's signifying their potential dual activity. Most favourable interactions were shown by compound 42.
Conclusion: The results obtained are encouraging for further exploration of the hit molecules for simultaneous treatment of the two diseases.
Background: Bernard Soulier Syndrome (BSS) is a rare autosomal recessive disorder due to deficiency or dysfunction of the glycoprotein GPIb-V-IX complex on the platelet surface. It is also known as hemorrhagiparous thrombocytic dystrophy or congenital hemorrhagiparous thrombocytic dystrophy. The patient usually presents with severe and prolonged bleeding along with characteristics of giant blood platelets and low platelet counts. Manifestations of BSS include epistaxis, gum bleeding, purpuric rashes, menorrhagia, rarely melena, and hematemesis. On the other hand, immune thrombocytopenic purpura (ITP) is an acquired autoimmune disorder in which there is accelerated platelet destruction and reduced platelet production. Isolated thrombocytopenia without fever, lymphadenopathy, and organomegaly usually lead to the diagnosis of immune thrombocytopenia.
Case presentation: A 20 years old female presented with complaints of recurrent episodes of epistaxis since childhood and menorrhagia during menarche. She was misdiagnosed as ITP elsewhere. Later, based on thorough clinical examination and investigation, the diagnosis was confirmed as BSS.
Conclusion: BSS should always be taken in the differential diagnosis of ITP, especially when persistent, refractory, and treated unsuccessfully with steroids or splenectomy.
Myocardial infarction and its sequalae remain the leading cause of death worldwide. Myocardial infarction (MI) survivors continue to live a poor quality of life due to extinguished heart failure. The post-MI period involves several changes at the cellular and subcellular levels, of which autophagy dysfunction. Autophagy is involved in the regulation of post-MI changes. Physiologically, autophagy preserves intracellular homeostasis by regulating energy expenditure and sources. Furthermore, dysregulated autophagy is considered the hallmark of the post-MI pathophysiological changes, which leads to the known short and long post-MI reperfusion injury sequalae. Autophagy induction strengthens self-defense mechanisms of protection against energy deprivation through economic energy sources and uses alternative sources of energy through the degradation of intracellular components of the cardiomyocyte. The protective mechanism against post-MI injury includes the enhancement of autophagy combined with hypothermia, which induces autophagy. However, several factors regulate autophagy, including starvation, nicotinamide adenine dinucleotide (NAD+), Sirtuins, other natural foods and pharmacological agents. Autophagy dysregulation involves genetics, epigenetics, transcription factors, small noncoding RNAs, small molecules, and special microenvironment. Autophagy therapeutic effects are signaling pathway-dependent and MI stage dependent. The paper covers recent advances in the molecular physiopathology of autophagy in post-MI injury and its potential target as a future therapeutic strategy.
Aims: The study aimed to assess the antihyperglycemic and antidyslipidemic activities of Artemisia mesatlantica.
Background: Artemisia mesatlantica is an endemic plant of Morocco used in traditional medicine as an alternative treatment for diabetes.
Objective: The study was designed to examine the antihyperglycemic and antidyslipidemicability of aqueous extract of Artemisia mesatlantica (AMAE) in experimental animal models.
Methods: The effect of the single and repeated oral administration (7 days of treatment) of AMAE (60 mg/kg) on blood glucose and lipid profile were assessed in normal and streptozotocin-induced diabetic rats. Furthermore, to confirm the antidyslipidemic effect of Artemisia mesatlantica, a model of hyperlipidemia induced by tyloxapol (Triton WR-1339) in rats was used.
Results: The AMAE (60 mg/kg) was able to significantly reduce glycaemia, improve lipid profile and increase hepatic glycogen content in STZ-induced diabetic rats. In addition, pretreatment of rats for 7 consecutive days with an aqueous extract of Artemisia mesatlantica (600 mg/kg) prior to tyloxapol injection prevented increases in plasma levels of total cholesterol, triglycerides and LDL-c.
Conclusion: From these observed results, it can be deduced that Artemisia mesatlantica possesses remarkable antidiabetic and antihyperlipidemic properties.
Introduction: Hypercholesterolemia is one of the main risk factors associated with atherosclerotic cardiovascular disease and coronary heart disease. Statins are the standard cholesterollowering treatment; however, they have shown, in clinical practice, a reduced adherence to therapy (<50%) and a modest achievement of the expected outcomes for treatment. This condition prompt scientific research to develop drugs with different mechanisms of action. In this regard, excellent results have been achieved with therapeutic use of monoclonal antibodies against PCSK9, enzyme involved in recycling of Low density lipoprotein receptors (LDLR) on the hepatocytes surface. Indeed, the reduction in receptor density caused by PCSK9 is associated with increased serum LDL levels.
Materials and methods: After the data extraction of all Local Health Authority (ASL) of Foggia patients (302) who received, in 2021, at least one administration of Alirocumab or Evolocumab, the therapeutic adherence was calculated, for each individual patient, by indirect method (calculation of the Medication Possession Ratio - MPR). According to scientific literature, patients were classified into: adherents (MPR>80%), average adherents (MPR between 40% and 80%) and non-adherents (MPR<40%). Patients were then stratified by gender and age groups (0-18, 19-49, 50-64, >65).
Results: The results show that, for both drugs (Alirocumab and Evolocumab), women are more adherent than men and the group of young adults (19-49 years old) is the one with the lowest adherence to therapy, 69% for Alirocumab and 56% for Evolocumab.
Conclusion: According to Italian Drug Agency (AIFA), poor therapeutic adherence is the main cause of ineffectiveness of drug therapies, and it is associated with increased hospitalizations, morbidity and mortality. Data obtained from this study allow to detect the categories of patients who need specific programs about the correct use of drugs, in order to increase therapeutic adherence and facilitate the achievement of the expected outcomes for treatment.
Introduction: Vitamin B deficiency causes cardiac hypertrophy, reduced cardiac contractility, and arrhythmias.The purpose of this study is to perform a network meta-analysis of randomized controlled trials of vitamin B supplements in a group of 150 patients who meet the eligibility criteria.The study also aims to describe the effect of synthetic multivitamins (pyridoxine, folic acid, and cyanocobalamin) on the laboratory findings reflecting the severity of chronic heart failure (cholesterol, glucose, and fibrinogen).
Methods: The experiment involved a group of people (150 individuals) diagnosed with chronic heart failure with reduced left ventricular ejection fraction. The study compared serum levels of B vitamins measured after the therapy and at baseline. The second part of the study focused on the assessment of the laboratory findings reflecting the severity of cardiovascular pathology and indicating an increased risk of vascular catastrophes.
Results: Clinical trials among patients diagnosed with chronic heart failure showed that the intake of synthetic forms of pyridoxine, folic acid, and cyanocobalamin slightly increases systolic, diastolic and central venous pressure while decreasing the heart rate and increasing LVEF. Thiamine acts as a vasodilator. It reduces the cardiac afterload and improves heart function.
Conclusion: The results obtained can be useful in terms of improving the comprehensive treatment strategy for chronic heart failure and further investigation of the effects produced by the intake of B vitamins.
β-thalassaemia is a genetic disorder resulting in a reduction or absence of β-globin gene expression. Due to the high prevalence of β-thalassaemia and the lack of available treatment other than blood transfusion and haematopoietic stem cell (HSC) transplantation, the disease represents a considerable burden to clinical and economic systems. Foetal haemoglobin has an appreciated ameliorating effect in β-haemoglobinopathy, as the γ-globin chain substitutes the β-globin chain reduction by pairing with the excess α-globin chain in β-thalassaemia and reduces sickling in sickle cell disease (SCD). BCL11A is a critical regulator and repressor of foetal haemoglobin. Downregulation of BCL11A in adult erythroblasts and cell lines expressing adult haemoglobin led to a significant increase in foetal haemoglobin levels. Disruption of BCL11A erythroid enhancer resulted in disruption of the BCL11A gene solely in the erythroid lineages and increased γ-globin expression in adult erythroid cells. Autologous haematopoietic stem cell gene therapy represents an attractive treatment option to overcome the immune complications and donor availability associated with allogeneic transplantation. Using genome editing technologies, the disruption of BCL11A to induce γ- globin expression in HSCs has emerged as an alternative approach to treat β-thalassaemia. Targeting the +58 BCL11A erythroid enhancer or BCL11A binding motif at the γ-gene promoter with CRISPR-Cas9 or base editors has successfully disrupted the gene and the binding motif with a subsequent increment in HbF levels. This review outlines the critical role of BCL11A in γ-globin gene silencing and discusses the different genome editing approaches to downregulate BCL11A as a means for ameliorating β-thalassaemia.
Background: Traditionally, the aerial parts of Rhamnus alaternus L. have been widely used in Mediterranean countries, including Morocco, to cure diabetes.
Aim: This study aimed to evaluate the antidiabetic effect of Rhamnus alaternus aqueous extract in streptozotocin(STZ)-induced diabetic rats.
Objective: This work aimed to evaluate the antihyperglycemic effect of Rhamnus alaternus aqueous extract (RAAE) in normal and diabetic rats. Then the phytochemical composition, antioxidant capacity, and potential toxicity of RAAE were also assessed.
Methods: The effects of acute (6 h) and subchronic (7 days) oral administration of RAAE (20 mg/kg) on blood glucose levels and lipid profiles were evaluated in normal and diabetic rats. Besides, a preliminary phytochemical screening, quantification of phenolic, flavonoid, and tannin contents as well as the antioxidant activity, using the DPPH method, were evaluated. Additionally, the toxicity of the aqueous extract (5 mg/kg) was also studied and the LD50 value was determined.
Results: RAAE (20 mg/kg) over 7 days of oral administration significantly decreased the blood glucose levels both in normal and diabetic rats. In diabetic rats, this extract also improved oral glucose tolerance. In addition, RAAE possessed significant antioxidant activity. According to preliminary phytochemical research, RAAE contains several chemical compounds, including alkaloids, polyphenols, flavonoids, cyanidins, anthraquinones, and sterols. On the other hand, the quantitative phytochemical study of the aqueous extract revealed a considerable amount of total phenolic compounds (497.93 ± 3.38 mg GAE/1g of RAAE), flavonoids (100.42 ± 0.32 mg RE/ g of RAAE), and tannins (14.32 ± 0.37 mg CE/1g of RAAE).
Conclusion: We conclude that RAAE exerts a significant antihyperglycemic effect in STZ-induced diabetic rats at a low dose. Indeed, more research is still required to support the use of this plant in the Moroccan population's diabetes care.
Aim: The current study aimed to evaluate the antidiabetic potential of Illicium verum fruits.
Background: Illicium verum fruits are frequently used by the Moroccan population in the treatment of diabetes.
Methods: The antihyperglycemic effect of the aqueous extract of Illicium verum fruits (AEIVF) in rats was assessed. The effects of AEIVF (20 mg/kg) on glycemia and lipid profile as well as its phytochemical and antioxidant properties were evaluated.
Results: In normal and diabetic rats, AEIVF reduced blood glucose levels 6 hours after administration. Furthermore, after 7 days of treatment, glycemia was lowered in diabetic rats, and this extract exhibited an antioxidant activity.
Conclusion: The study shows that Illicium verum possesses a potent antidiabetic activity. In addition, the toxicity of AEIVF was evaluated and the LD50 value was found to be greater than the 2 g/kg dose.
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