Cardiovascular and Hematological Disorders - Drug Targets最新文献

Introduction: There is a high incidence of venous thromboembolism (VTE) in patients with Multiple Myeloma (MM), however; until now, the exact mechanisms behind VTE in MM are unknown, and some of the elements that may play a significant role are the treatment with an immunomodulator (IMiD) and acquired resistance to activated protein C (APC).

Objective: The study aims to reveal the possible mechanisms linked to the reduced antithrombotic activity of APC associated with thalidomide.

Methods: The molecular docking approach was used to ascertain the in silico inhibitory potential of thalidomide on the APC protease domain in the architecture of the catalytic triad and its interaction with major substrate binding sites.

Results: The coupling showed that the inhibitory activity of thalidomide depends on the induction of structural changes in the protease domain of APC, at the level of the Ser/His/Asp catalytic triad, as a result of a significant increase between the distances of CαAsp102 and Cα Ser195 (11.175 angstroms, increase 14.83%) and between CαSer195 and CαHis57 (9.478 angstroms, increase 13.78 %). This can result in an inefficient transfer of the proton between these residues, the other possible mechanism of inhibition, is a potential reduced binding of the substrate as a result of a direct interaction through a carbon-hydrogen bond on His57, an H-bond on Arg306, and a carbon hydrogen bond on Arg506.

Conclusion: We demonstrate the in silico inhibitory potential of thalidomide on APC, through two possible inhibition mechanisms, a pathophysiologically relevant finding to understand the factors that can affect the stability and functions of APC in vivo.

Aims: The study aimed to analyze the analgesic activity of Cistus ladanifer L.

Background: Cistus ladanifer L. is a fragrant shrub of the Cistaceae family widespread in the Mediterranean basin, it has various biological activities, including antidiabetic and antihypertensive effects.

Objectives: The objective of this work was to study the phytochemical profile, the acute toxicity and the analgesic power of the ethanolic extract of the species Cistus ladanifer L. (C. ladanifer) collected in Northern Morocco.

Methods: The evaluation of antinociceptive activity in mice was performed using two validated models, the formalin-induced paw-licking model and the acetic acid-provoked writhing test.

Results: According to the results, five phenolic compounds were identified in the ethanolic extract by HPLC-MS/MS. As regards the acute toxicity study, the results showed no mortality or clinical symptoms in mice treated to compare the control group at doses up to 5,000 mg/kg BW. Regarding the analgesic effect, the ethanolic extract at the doses of 400 and 800 mg/kg, BW showed a statistically significant (p <0.05) and dose-dependent analgesic effect in two nociceptive tests. On the other hand, in the syrup of ethanolic extract at the dose of 800 mg/kg, BW expressed the most superior pain-inhibiting effect in both tests, producing an analgesic effect equivalent to that of the reference drug (indomethacin).

Conclusion: These findings provide pharmacological justification that might aid in the development of a natural anti-nociceptive medication as an alternative to chemical analgesic drugs.

Background: Preterm labor is one of the most important causes of hospitalization during pregnancy and can lead to serious complications in neonates.

Objective: This study aims to compare the effect of transdermal nitroglycerin (TNG) patches and sublingual tablets of Isosorbide dinitrate (ISD) for the prevention of preterm delivery.

Methods: A total of 110 healthy pregnant women aged 18-35 years with a healthy and alive fetus and gestational age between 24-34 weeks who had at least 8 regular uterine contractions per hour were included in this single-blinded clinical trial. After exclusion, the women were randomly divided into TNG (n = 50) and ISD (n = 49) groups. After the first dose of medication (TNG or ISD), patients who developed complications such as hypotension, headache, or both, were also excluded from the study.

Results: A total of 58 patients completed the treatment course (29 patients in each group). A significant difference in delayed preterm labor and recovery time was reported between the TNG and ISD groups.

Conclusion: Complications and the number of contractions were not statistically different in the two groups. We concluded that the TNG patch is more effective than ISD in delaying labor. Both drugs are likely to have a similar incidence of side effects.

Background: Natural products and their derived pure phytochemicals have enormous potential to treat human disorders and associated secondary complications. Natural products are widely consumed by humans due to their rich phytochemical content, diverse therapeutic potential and cost-effectiveness compared to allopathic medicine. Flavonoids are a well-known class of polyphenolic compounds widely present in the plant kingdom. Tectochrysin is an important class of dietary flavonoids present in foods and fruits. Tectochrysin has anti-tumor, anti-Alzheimer's, and antimicrobial activities in medicine. Pharmacological studies have signified the biological application of tectochrysin in health sectors for the treatment of hepatic and gastrointestinal complications.

Methods: This current review summarizes the updated scientific information on the medicinal importance and pharmacological activities of tectochrysin. Scientific information on tectochrysin was collected from PubMed, Science Direct, Google Scholar, and Google with some additional resources, including books, dissertations, and scientific reports in the present work. Collected scientific information was further categorized into medicinal uses, pharmacological activities, and analytical aspects in the present paper. Furthermore, detailed pharmacological activities of tectochrysin were discussed in the present work, with analytical aspects used for the separation, isolation and identification of tectochrysin in order to explore its therapeutic potential in medicine.

Results: Phytochemical analysis of propolis, Alpinia oxyphylla and Lychnophora markgravii led to the isolation of tectochrysin. This present work signified the anticancer activity of tectochrysin on prostate cancer, human colon cancer, and breast cancer. Moreover, its anti-osteoporosis, antiinflammatory, anti-oxidant, anti-microbial, anti-diarrheal, and hepatoprotective activity were also discussed in the present work. Further effectiveness of tectochrysin in Alzheimer's disease, SARSCoV- 2, nitric oxide production, aryl hydrocarbon receptor, and age-related diseases was further explored in the present work. It has been found that experimental animal data also supports its antimicrobial, anti-oxidant, and metabolic functions. Analytical data indicated its separation, isolation, and identification in different samples.

Conclusion: Scientific data presented in this review signifies the biological importance and therapeutic potential of tectochrysin in medicine.

Dilated cardiomyopathy (DCM) is distinguished by ventricular chamber expansion, systolic dysfunction, and normal left ventricular (LV) wall thickness, and is mainly caused due to genetic or environmental factors; however, its aetiology is undetermined in the majority of patients. The focus of this work is on pathogenesis, small animal models, as well as the herbal medicinal approach, and the most recent advances in imaging modalities for patients with dilated cardiomyopathy. Several small animal models have been proposed over the last few years to mimic various pathomechanisms that contribute to dilated cardiomyopathy. Surgical procedures, gene mutations, and drug therapies are all characteristic features of these models. The pros and cons, including heart failure stimulation of extensively established small animal models for dilated cardiomyopathy, are illustrated, as these models tend to procure key insights and contribute to the development of innovative treatment techniques for patients. Traditional medicinal plants used as treatment in these models are also discussed, along with contemporary developments in herbal therapies. In the last few decades, accurate diagnosis, proper recognition of the underlying disease, specific risk stratification, and forecasting of clinical outcome, have indeed improved the health of DCM patients. Cardiac magnetic resonance (CMR) is the bullion criterion for assessing ventricular volume and ejection fraction in a reliable and consistent direction. Other technologies, like strain analysis and 3D echocardiography, have enhanced this technique's predictive and therapeutic potential. Nuclear imaging potentially helps doctors pinpoint the causative factors of left ventricular dysfunction, as with cardiac sarcoidosis and amyloidosis.

Aims: The study aimed to assess the antihyperglycemic activity of Pelargonium graveolens.

Background: Pelargonium graveolens (P. graveolens) (Geraniaceae) is a medicinal plant frequently used in traditional medicine in Morocco and Algeria as remedy against a multitude of illnesses. Interestingly, it is used in the Moroccan pharmacopeia for managing diabetes.

Objective: The current study was carried out in order to assess the antihyperglycemic activity of P. graveolens in normal and streptozotocin(STZ)-induced diabetic rats, as well as to evaluate the acute toxicity of the leaves aqueous extract of Pelargonium graveolens (PGLAE).

Methods: The therapeutic effect of PGLAE at a dose of 40 mg/kg on blood glucose levels was investigated in normal and STZ-induced diabetic rats after a single oral (6h) and a repeated (15 days) oral administration. The acute toxicity of the PGLAE was examined in accordance the OECD test guideline. Post-treatment, body weight, signs of toxicity, and/or mortality were observed for 14 days. Further assays such as the oral glucose tolerance test, histopathological examination and antioxidant activity was also performed according to standard protocols.

Results: Findings exhibited that both single and repeated oral doses of PGLAE (40 mg/kg) produced significant reduction of blood glucose levels in normal and diabetic rats. All treated animals survived and no apparent adverse effects were observed during the duration of the acute toxicity study. Importantly, oral LD50 of PGLAE was greater than 2000 mg/kg BW. Furthermore, a remarkable influence on glucose tolerance was also noticed after PGLAE treatment. Moreover, PGLAE was able to improve histopathological structure of liver and possesses a potential antioxidant effect in vitro.

Conclusion: In conclusion, this study reports the antidiabetic effect of PGLAE in rats supporting then its traditional use for the management of diabetes.

Background: Patients with hemophilia have a hypocoagulable state and less chances of thrombus formation. Therefore, expected to have a lower cardiovascular mortality than the general population. The lower cardiovascular mortality can be explained by less chances of thrombus formation due to hypocoagulability.

Case presentation: Here we present a case of a 42-year-old male patient presented with severe chest pain radiating to back for 4 days. ECG was suggestive of recent acute anteroseptal myocardial infarction. There was a history of receiving intravenous recombinant factor VIII, 1 hour prior to the onset of chest pain for knee joint swelling. The occurrence of acute coronary syndromes in patients with hemophilia A is uncommon and rarely reported.

Conclusion: Here we report a patient of severe hemophilia A who developed acute myocardial infarction after administration of recombinant factor VIII.

Purpose: Acute Coronary Syndrome (ACS) is currently the leading cause of death in industrialized countries. Morbidity after ACS includes physical and mental disorders affecting the patient's whole life situation and Quality of Life (QoL). The main aim of the study was to assess QoL and depression among post-ACS patients.

Methods: This was a cross-sectional observational study. A total of 112 patients who fulfilled the inclusion criteria were included in this study. A semi-structured questionnaire was administered to the patients to collect data from the patients. In this study, men and women aged 18 - 80 with ACS; patients diagnosed with Non-ST Segment Elevated Myocardial Infarction (NSTEMI) or STEMI or Angina Pectoris were included. Patients with severe mental, and physical illness and dementia were excluded from the study. QoL and depression assessment was done by RAND 36-Item Health Survey and Hamilton Depression Rating scale, respectively.

Results: Among 112 post-ACS patients, 78 patients were males, and 38 patients were females. The mean age of the study population was 64.25 ± 9.029 and with most individuals in the category of 61 -70 years. The majority of study populations were married (71.5%) and lived with their families (92.9%). In this study group, 42.9 % of the population reported at least high school education (SSLC) and 54.5% were full-time employees. Most of the patients (91.1%) were taking the medication regularly, while 55.4% of patients reported regular compliance with the follow-up. This study identified that, among various factors, older age, female gender, lower income, unemployment, low education status, poor compliance with medication, and depressive symptoms led to poor QoL.

Conclusion: This study confirms a negative correlation between depressive symptoms and QoL. This study's results reveal the magnitude of depression that is prevalent in the primary health care clinic that goes undiagnosed and unmanaged. Hence, it is recommended to properly screen depressive symptoms in ACS patients. Therefore, concurrently, better QoL can be achieved by managing both depression and ACS.