Augmented weighted K-means grey wolf optimizer: An enhanced metaheuristic algorithm for data clustering problems.

This study presents the K-means clustering-based grey wolf optimizer, a new algorithm intended to improve the optimization capabilities of the conventional grey wolf optimizer in order to address the problem of data clustering. The process that groups similar items within a dataset into non-overlapping groups. Grey wolf hunting behaviour served as the model for grey wolf optimizer, however, it frequently lacks the exploration and exploitation capabilities that are essential for efficient data clustering. This work mainly focuses on enhancing the grey wolf optimizer using a new weight factor and the K-means algorithm concepts in order to increase variety and avoid premature convergence. Using a partitional clustering-inspired fitness function, the K-means clustering-based grey wolf optimizer was extensively evaluated on ten numerical functions and multiple real-world datasets with varying levels of complexity and dimensionality. The methodology is based on incorporating the K-means algorithm concept for the purpose of refining initial solutions and adding a weight factor to increase the diversity of solutions during the optimization phase. The results show that the K-means clustering-based grey wolf optimizer performs much better than the standard grey wolf optimizer in discovering optimal clustering solutions, indicating a higher capacity for effective exploration and exploitation of the solution space. The study found that the K-means clustering-based grey wolf optimizer was able to produce high-quality cluster centres in fewer iterations, demonstrating its efficacy and efficiency on various datasets. Finally, the study demonstrates the robustness and dependability of the K-means clustering-based grey wolf optimizer in resolving data clustering issues, which represents a significant advancement over conventional techniques. In addition to addressing the shortcomings of the initial algorithm, the incorporation of K-means and the innovative weight factor into the grey wolf optimizer establishes a new standard for further study in metaheuristic clustering algorithms. The performance of the K-means clustering-based grey wolf optimizer is around 34% better than the original grey wolf optimizer algorithm for both numerical test problems and data clustering problems.

Reserpine Induces Apoptosis and Cell Cycle Arrest in Hormone Independent Prostate Cancer Cells through Mitochondrial Membrane Potential Failure.

BACKGROUND: Reserpine, an indole alkaloid commonly used for hypertension, is found in the roots of Rauwolfia serpentina. Although the root extract has been used for the treatment of cancer, the molecular mechanism of its anti-cancer activity on hormonal independent prostate cancer remains elusive. METHODS: we evaluated the cytotoxicity of reserpine and other indole alkaloids, yohimbine and ajmaline on Prostate Cancer cells (PC3) using MTT assay. We investigated the mechanism of apoptosis using a combination of techniques including acridine orange/ethidium bromide staining, high content imaging of Annexin V-FITC staining, flow cytometric quantification of the mitochondrial membrane potential and Reactive Oxygen Species (ROS) and cell cycle analysis. RESULTS: Our results indicate that reserpine inhibits DNA synthesis by arresting the cells at the G2 phase and showed all standard sequential features of apoptosis including, destabilization of mitochondrial membrane potential, reduced production of reactive oxygen species and DNA ladder formation. Our in silico analysis further confirmed that indeed reserpine docks to the catalytic cleft of anti-apoptotic proteins substantiating our results. CONCLUSION: Collectively, our findings suggest that reserpine can be a novel therapeutic agent for the treatment of androgen-independent prostate cancer.

In silico pharmacokinetic and molecular docking studies of small molecules derived from Indigofera aspalathoides Vahl targeting receptor tyrosine kinases.

Angiogenesis is the formation of new blood vessels from preexisting vascular network that plays an important role in the tumor growth, invasion and metastasis. Anti-angiogenesis targeting tyrosine kinases such as vascular endothelial growth factor receptor 2 (VEGFR2) and platelet derived growth factor receptor ß (PDGFRß) constitutes a successful target for the treatment of cancer. In this work, molecular docking studies of three bioflavanoid such as indigocarpan, mucronulatol, indigocarpan diacetate and two diterpenes namely erythroxydiol X and Y derived from Indigofera aspalathoides as PDGFRß and VEGFR2 inhibitors were performed using computational tools. The crystal structures of two target proteins were retrieved from PDB website. Among the five compounds investigated, indigocarpan exhibited potent binding energy ΔG = -7.04 kcal/mol with VEGFR2 and ΔG = -4.82 with PDGFRß compared to commercially available anti-angiogenic drug sorafenib (positive control). Our results strongly suggested that indigocarpan is a potent angiogenesis inhibitor as ascertained by its potential interaction with VEGFR2 and PDGFRß. This hypothesis provides a better insight to control metastasis by blocking angiogenesis.

Effect of iron deficiency on glycation of haemoglobin in nondiabetics.

BACKGROUND: Protein glycation is a spontaneous reaction that is believed to play a key role in the pathogenesis of many clinical disorders. The glycation of proteins is enhanced by elevated glucose concentrations. The major form of protein glycation with a clinical consideration is glycated haemoglobin (HbA1c). The HbA1c fraction is abnormally elevated in chronic hyperglycaemic diabetic patients and it correlates positively with the glycaemic control. However, increased glycated haemoglobin levels have been documented in iron de.ciency anaemic patients without any history of diabetes. AIMS AND OBJECTIVE: The aim of this study was to determine the effect of IDA on the HbA1c levels in nondiabetic patients, so as to consider IDA as an important factor which influenced the HbA1c levels, while monitoring the glycaemic status of diabetics. METHODOLOGY: Fifty non-diabetic, anaemic patients and 50 age-matched healthy subjects were enrolled in this study. The patients who had glucose tolerance abnormalities (impaired glucose tolerance or diabetes mellitus), haemoglobinopathies, haemolytic anaemia, infestation, chronic alcohol ingestion and chronic renal failure were excluded from the study. Haematologic investigations were done and the fasting and postprandial glucose and HbA1c levels were measured in all the subjects. RESULTS: The mean HbA1c (7.6 ± 0.5%) level in the patients with IDA was higher than that in the control group (5.5% ± 0.8) (p < 0.001). There were no differences in the levels of fasting and postprandial glucose between the IDA and the control groups (p > 0.05). The haemoglobin, serum ferritin, fasting and postprandial glucose, and the HbA1c levels were normal in the control group (p > 0.05). CONCLUSION: HbA1c is not affected by the blood sugar levels alone, and there are various confounding factors when HbA1c is measured, especially that of iron de.ciency, which is the commonest of the de.ciency diseases worldwide. It is hence prudent to rule out IDA before making a therapeutic decision, based on the HbA1c levels.

Prescribing pattern of anti-seizure medications (ASMs): an evaluation of extent of xanthine co-medication.

This study was conducted to evaluate the prescribing pattern of anti-seizure medications (ASMs) at a tertiary care hospital. The extent and pattern of concurrently used medications for co-exiting illnesses was also studied. Attention was focussed in particular on co-existence of bronchial asthma with epilepsy and co-medication of ASMs with xanthines. The study was carried out at the Central Pharmacy and at the Medical Records Department. Data analysis at the central pharmacy showed 3.98% prescriptions for ASMs, with maximum number for males. More drugs were prescribed during the second decade of life and there were 2.17 drugs per prescription. The data for pattern and extent of use of ASMs along with polytherapy and concurrently used medications revealed the highest number of prescriptions for phenytoin, maximum number with single ASM, and phenytoin with phenobarbitone as most frequently prescribed combination. Co-administration of ASMs with respiratory medications was found in 2.47%, with 38.8% prescriptions having xanthines prescribed in them. Xanthines, the well known CNS stimulants, a property attributed to their adenosine receptor antagonistic activity, are considered potential seizurogenic agents. The results of the present preliminary survey show an indirect evidence for co-existence of epilepsy with asthma along with the extent of co-medication of ASMs with xanthines. Results indicate the need for further studies to evaluate the consequences of co-medication of ASMs with xanthines.