Identification of therapeutic phytochemicals targeting B-cell lymphoma 2 (BCL2) as anti-acute myeloid leukemia agents: An in-silico approach

ackground: Acute myeloid leukemia (AML) is a deadly cancer. B cell lymphoma 2 (BCL2) is frequently upregulated in AML and plays a vital role in the viability of both AML and AML stem cells. This study aimed to identify novel phytochemicals against BCL2 and evaluate their pharmacokinetics and toxicity prediction using in-silico tools.Methods: In-silico screening of phytochemicals against BCL2 active site using the PyRx0.8 AutoDock tool, followed by in silico pharmacokinetic and toxicity predictions was performed. Protein-protein interaction analysis was performed using the STRING database for assessing the interactions between BCL2 and neighboring interacting proteins.Results: In total, 1106 terpenoid compounds were screened to evaluate their binding affinity toward BCL2. Five natural compounds demonstrated strong binding to the BCL2 protein after extensive screening, detailed interaction analysis, and visual inspections. Notably, these compounds had higher binding energies than the positive control (venetoclax). In addition, these compounds were found to bind to key BCL2 residues and possess good drug-like properties.Conclusions: The identified phytochemicals represent an important initial step in drug discovery for AML management. Experimental validation is required to optimize the identified phytochemicals as potential BCL2 inhibitors

Rancang Bangun Sistem Monitoring Kelembaban Pada Lahan Pertanian Bawang Merah

Bawang merah merupakan tanaman hortikultura yang berumur pendek dan memiliki nilai komersial yang tinggi dengan resiko yang tinggi. Sebagai tanaman yang banyak dimanfaatkan masyarakat, bawang merah telah lama dibudidayakan secara intensif oleh petani.Meskipun banyak produsen bawang merah saat ini, namun masih menghadapi kendala dalam budidayanya,terutama pada pengairan sebab tumbuhan bawang merah merupakan umbi , oleh karna itu tumbuhan itu memerlukan air yang lumayan semenjak perkembangan dini sampai menjelang panen.kelembaban tanah menjadi perhatian utama, karena hasil bawang merah tidak optimal tanpa pemantauan kelembaban tanah. Inilah yang melatarbelakangi dibangunnya aplikasi yang dapat memonitoring kelembaban tanah pada lahan bawang secara real time Rancang Bangun Aplikasi Monitoring Kelembaban Pada Lahan Bawang Merah yang dicoba mencakup, Membuat sistem yang bisa membaca kelembaban tanah dengan memakai Soil Moisture Sensor tipe YL- 69 serta Membuat sistem yang bisa membagikan data berbentuk pemberitahuan melewati aplikasi terhadap petani alhasil bisa dilakukan penyiraman.dibuatnya System Monitoring Kelembaban Pada Lahan Bawang Merah ini di buat dengan tujuan guna mempermudah petani memonitoring nilai kelemaban tanah melalui aplikasi secara realtime. menggunakan sensor yl69 yang dikoneksikan dengan ESP32 ,kemudian Sensor Soil Moistur akan membaca serta mengirim informasi ke Firebase.Setelah itu firebase akan mengirimkan data ke aplikasi smartphone yang telah di buat dan Buzzer akan menyala Ketika kelembaban tidak memenuhi 50-70 %. Riset ini sukses mewujudkan Rancang Bangun Aplikasi Monitoring Kelembaban Pada Lahan Bawang Merah dengan membagikan data berbentuk notifikasi dan nilai kelembaban tanah pada petani melewati smartphone, alhasil petani bisa melaksanakan penyiraman bila kelembaban tanah kurang dari 50%.Tidak ditemukan nilai error pada perbandingan antara firebase dan aplikasi pada smartphone

Association of serum asymmetric dimethyl-arginine and troponin I levels as a risk of myocardial infarction in thalassemia

Background: The current study evaluated level of serum asymmetric dimethylarginine (ADMA) and its association to cardiac biomarkers in thalassemia patients for early diagnosis of abnormality in myocardial infarction. Subjects and methods: This study was conducted on 80 subjects divided into four groups each with 20 subjects. Group I: Control: healthy subjects. Group II: Myocardial infarction: Patients with elevated serum troponin T. Group III: thalassemia patients. Group IV: thalassemia with myocardial infarction patients: Included 20 thalassemia patients with Myocardial infarction. Serum samples were subjected for assay of creatine kinase (CK:MB), Lactate dehydrogenase, troponin I ,ADMA, Serum MDA level was determined. Results: Data obtained showed that serum CKMB, LDH1, AST, Troponin T and ADMA levels were significant elevated in MI with or without Thalassemia compared with control groups. Serum MDA was statistically significantly elevated in MI with or without Thalassemia compared with control groups. The serum level of troponin T showed an area under curve (AUC) of 0.92 ,(sensitivity 91.0 % and specificity, 88%). Also, the ADMA supported the diagnostic profile, showing an AUC of 0.85 with (sensitivity, 92.0%; specificity, 91,9%). Conclusion: Serum ADMA is sensitive marker for incidence of MI in thalassemia patients.Keywords: CKMB, LDH1, AST, Troponin T, asymmetric dimethylarginie, Thalassemia

Target-based virtual screening and molecular dynamics approach to identify potential antileishmanial agents through targeting UvrD-like helicase ATP-binding domain

Background: About 0.7-1.0 million people worldwide have been suffering from Leishmaniasis. It falls under a neglected tropical disease (NTD) and is transmitted by biting infected female phlebotomine sandflies. The implication of “the NTD road map: together towards 2030” in the infection-prone regions worldwide has curtailed morbidity to a greater extent. However, limited options in antileishmanial oral and topical drugs must decipher more therapeutically efficacious agents to cure and eradicate the disease. Methods: Virtual screening based on structure, docking, & molecular dynamics approaches were adopted to identify potential lead molecules against UvrD-like helicase of Leishmania donovani from the MCULE database. Lipinski rule of five, N/O atoms (1-15), number of rings (1-2), HBDs (4-5), and HBAs (5-10) were applied as initial filters of SBVS. AutoDock Vina and GROMACS packages were used for docking and MD simulations, respectively. Results: Initial filters of SBVS workflow yielded 93885 ligand hits out of 100 plus million investigational ligands. Following the toxicology test, 28 ligands were gotten that were additional reduced to molecules (17) when accepted done the BOILED Egg model of the ADME. Six molecules were shortlisted with zero violation compliance of drug-likeness further than Lipinski RO5 viz., Egan, Veber, Muegge, Ghose, & bioavailability score having ΔG (-6.7 to -7.4 kcalmol-1) lesser than reference inhibitor miltefosine (-4.9 kcalmol-1). The stability of MCULE-5754880195-0-2 was found to be greater than the known inhibitor and ligand molecules mentioned above.Conclusion:  MCULE-5754880195-0-2 has all therapeutic features by way of an admirable oral drug molecule & could be encouraging in Leishmaniasis prevention & treatment.Keywords: UvrD-like helicase; ADME; Leishmaniasis; MCULE database; SBVS; Docking; BOILED Egg; MD simulation; ATP-binding domain

The sensitivity of Na+, K+ ATPase as an indicator of blood diseases

Background: Blood-related hereditary diseases are widespread in Eastern and SouthWestern regions of Saudi Arabia until recently. In this study, we used Na+, K+ATPase as an enzymatic indicator for the diagnosis of the diseases.Materials and methods: Individuals with different blood diseases (iron deficiency (n=13), anemia (n=14), thalassemia (n=16) and sickle cell anemia (n=12) were studied for Na+, K+-ATPase activity in the plasma membrane of red blood cell and compared with those of the healthy ones (n=20) of the same age and gender living in Jeddah, Saudi Arabia.Results: There was a significant elevation in the specific activity of Na+, K+ATPase in individuals with anemia compared with those of control (0.0094 + 0.001 nmol / mg protein/min versus 0.0061 0.001). On the other hand, there was a significant reduction in enzyme activity in thalassemia (0.0028 0.002 nmol / mg protein/min) and sickle cell anemia cases (0.0042 0.001 nmol / mg protein/min) compared to the control group. The cut off value for Na+, K+ATPase activity is 0.005 μmol Pi/minshowing 94% sensitivity and 93% specificity for the differentiation of blood abnormality.Conclusion: It can be recommended that the activity of Na+, K+-ATPase can be used for the diagnosis of individuals with blood diseases/disorders.Keywords: Na+, K+-ATPase, red blood cell, plasma membrane, iron deficiency anemia, thalassemia, sickle cell anemia, indicato

Association of serum asymmetric dimethyl-arginine and troponin I levels as a risk of myocardial infarction in thalassemia

Background: The current study evaluated level of serum asymmetric dimethylarginine (ADMA) and its association to cardiac biomarkers in thalassemia patients for early diagnosis of abnormality in myocardial infarction. Subjects and methods: This study was conducted on 80 subjects divided into four groups each with 20 subjects. Group I: Control: healthy subjects. Group II: Myocardial infarction: Patients with elevated serum troponin T. Group III: thalassemia patients. Group IV: thalassemia with myocardial infarction patients: Included 20 thalassemia patients with Myocardial infarction. Serum samples were subjected for assay of creatine kinase (CK:MB), Lactate dehydrogenase, troponin I ,ADMA, Serum MDA level was determined. Results: Data obtained showed that serum CKMB, LDH1, AST, Troponin T and ADMA levels were significant elevated in MI with or without Thalassemia compared with control groups. Serum MDA was statistically significantly elevated in MI with or without Thalassemia compared with control groups. The serum level of troponin T showed an area under curve (AUC) of 0.92 ,(sensitivity 91.0 % and specificity, 88%). Also, the ADMA supported the diagnostic profile, showing an AUC of 0.85 with (sensitivity, 92.0%; specificity, 91,9%). Conclusion: Serum ADMA is sensitive marker for incidence of MI in thalassemia patients

Changes in erythrocyte ATPase activity under different pathological conditions

Background: Studies have shown that Na+-K+ ATPase activity was altered in disrupted red blood cell membranes and this enzyme is believed to be the site of active transport of Na+ and K+ in intact red blood cells. The enzyme is often referred to as Na+- K+ pump because it pumps Na+ out and K+ into the cell against gradients with the concomitant hydrolysis of intracellular ATP.Objective: The aim of this study was to find out the possibility of using Na+-K+-ATPase activity as a biomarker for the diagnosis of individuals with different physiological conditions.Materials and methods: The activity of Na+-K+ ATPase was determined in blood samples collected from different pathological and physiological conditions such as pregnancy, smoking, diabetes and renal dysfunction compared with healthy subjects matched for age and sex.Results: The Na+-K+ ATPase activity in pregnancy (0.094 ± 0.0051 μM Pi/min. mg protein), smoking (0.064 ± 0.0011 μM), diabetes (0.047 μM 0.002 μM) and kidney disease (0.069 ± 0.0014 μM) was higher compared to the measurements in healthy individuals (0.0081 ± 0.0031 μM).Conclusion: Na+- K+ATPase specific activity is a biomarker for the diagnosis of individuals with different physiological diseases.Keywords: Na+-K+ATPase, red blood cell, pregnancy, smoking, diabetes, kidney diseases

Comparative Analysis of the Performance of Popular Sorting Algorithms on Datasets of Different Sizes and Characteristics

Abstract: The efficiency and performance of sorting algorithms play a crucial role in various applications and industries. In this research paper, we present a comprehensive comparative analysis of popular sorting algorithms on datasets of different sizes and characteristics. The aim is to evaluate the algorithms' performance and identify their strengths and weaknesses under varying scenarios. We consider six commonly used sorting algorithms: QuickSort, TimSort, MergeSort, HeapSort, RadixSort, and ShellSort. These algorithms represent a range of approaches and techniques, including divide-and-conquer, hybrid sorting, and simple comparison-based methods. To assess their performance, we employ a diverse set of datasets, including the Iris dataset (1K), student dataset (5.8K), Wine dataset (6.5K), Uniform (10K), Normal (10K), Exponential (10K), Bimodal (10K), Yelp dataset (10K), MNIST dataset (42K), Uniform (100K), Normal (100K), Exponential (100K), Bimodal (100K), Uniform (500K), Normal (500K), Exponential (500K), Bimodal (500K), Uniform (1M), Normal (1M), Exponential (1M), and Bimodal (1M). These datasets cover a wide range of sizes and characteristics, allowing us to analyze the algorithms' performance across different dimensions. We measure and compare several key metrics, including execution time, memory usage, algorithmic complexity and stability. By analyzing these metrics, we gain insights into the efficiency and suitability of each algorithm for different dataset sizes and characteristics. We also discuss the implications of the findings in practical applications. Our results reveal important trade-offs among the sorting algorithms. While some algorithms excel in certain scenarios, others demonstrate better scalability or memory efficiency. We identify the best-performing algorithms for specific dataset characteristics and highlight their strengths and limitations. This research can assist developers and practitioners in selecting appropriate sorting algorithms based on their specific requirements and dataset characteristics. In conclusion, this comparative analysis provides a valuable contribution to the understanding of sorting algorithm performance. The findings contribute insights into the efficiency and suitability of popular sorting algorithms across datasets of different sizes and characteristics. By evaluating key metrics and discussing the implications, we offer guidance for selecting the most appropriate sorting algorithm in various practical scenarios

The sensitivity of Na+, K+ ATPase as an indicator of blood diseases.

Background: Blood-related hereditary diseases are widespread in Eastern and SouthWestern regions of Saudi Arabia until recently. In this study, we used Na+, K+ATPase as an enzymatic indicator for the diagnosis of the diseases. Materials and methods: Individuals with different blood diseases (iron deficiency (n=13), anemia (n=14), thalassemia (n=16) and sickle cell anemia (n=12) were studied for Na+, K+-ATPase activity in the plasma membrane of red blood cell and compared with those of the healthy ones (n=20) of the same age and gender living in Jeddah, Saudi Arabia. Results: There was a significant elevation in the specific activity of Na+, K+ATPase in individuals with anemia compared with those of control (0.0094 + 0.001 nmol / mg protein/min versus 0.0061 \ub10.001). On the other hand, there was a significant reduction in enzyme activity in thalassemia (0.0028 \ub1 0.002 nmol / mg protein/min) and sickle cell anemia cases (0.0042 \ub1 0.001 nmol / mg protein/min) compared to the control group. The cut off value for Na+, K+ATPase activity is 0.005 \u3bcmol Pi/minshowing 94% sensitivity and 93% specificity for the differentiation of blood abnormality. Conclusion: It can be recommended that the activity of Na+, K+-ATPase can be used for the diagnosis of individuals with blood diseases/disorders

Targeting NF-κB signaling cascades of glioblastoma by a natural benzophenone, garcinol, via in vitro and molecular docking approaches

Glioblastoma multiforme (GBM) is regarded as the most aggressive form of brain tumor delineated by high cellular heterogeneity; it is resistant to conventional therapeutic regimens. In this study, the anti-cancer potential of garcinol, a naturally derived benzophenone, was assessed against GBM. During the analysis, we observed a reduction in the viability of rat glioblastoma C6 cells at a concentration of 30 µM of the extract (p < 0.001). Exposure to garcinol also induced nuclear fragmentation and condensation, as evidenced by DAPI-stained photomicrographs of C6 cells. The dissipation of mitochondrial membrane potential in a dose-dependent fashion was linked to the activation of caspases. Furthermore, it was observed that garcinol mediated the inhibition of NF-κB (p < 0.001) and decreased the expression of genes associated with cell survival (Bcl-XL, Bcl-2, and survivin) and proliferation (cyclin D1). Moreover, garcinol showed interaction with NF-κB through some important amino acid residues, such as Pro275, Trp258, Glu225, and Gly259 during molecular docking analysis. Comparative analysis with positive control (temozolomide) was also performed. We found that garcinol induced apoptotic cell death via inhibiting NF-κB activity in C6 cells, thus implicating it as a plausible therapeutic agent for GBM