Johra Khan

Early identification of coronary artery disease (CAD) is important for reducing mortality and improving patient outcomes. This study aimed to evaluate the usefulness of neutrophil-to-lymphocyte ratio (NLR) and creatine kinase-MB (CK-MB) as predictive biomarkers of CAD in patients suspected of requiring percutaneous coronary intervention (PCI). This hospital-based retrospective cross-sectional study included patients admitted to Prince Abdullah Bin Abdulaziz Bin Musaed Cardiac Centre (PAAMCC) between 1 July and 30 November 2023. Clinical, hematological, and biochemical data were collected from electronic medical records. Patients were divided into two groups according to NLR level: normal (≤ 3.0) and high (> 3.0). A total of 276 patients were included, comprising 256 males (92.8%) and 20 females (7.2%), with a mean age of 48.09 ± 7.97 years. Among them, 157 patients (56.9%) underwent PCI and were classified as having CAD. NLR was significantly associated with PCI (P < 0.001), and 143 of the 157 patients who underwent PCI (91.1%) had a high NLR level. Significant differences were also observed between the normal and high NLR groups in serum levels of CK, CK-MB, troponin I, and LDL (P < 0.001). Multivariate analysis showed that both NLR and CK-MB were significant predictors of PCI, with adjusted odds ratios (AORs) of 3.08 (P < 0.001) and 1.10 (P = 0.001), respectively. In conclusion, NLR and CK-MB were independently associated with PCI among patients from the Northern Border Region of Saudi Arabia. However, further studies are needed to confirm the clinical value of NLR as an effective diagnostic biomarker for CAD.

The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the current coronavirus disease 2019 (COVID-19) pandemic, which has disclosed alarming challenges to global health. The disease demonstrates several clinical issues, from mild symptoms to severe acute respiratory-related problems, including multi-organ failure. The virus is key in COVID-19’s pathogenesis, triggering different inflammatory responses. A well-known inflammatory biomarker, C-reactive protein (CRP), has become a possible diagnostic and prognostic marker in COVID-19 patients. This review aims to explain CRP in COVID patients and disease progression. It also shows how it can have a predictive value for clinical outcomes and potential therapeutic purposes. Additionally, we address the limitations and offer recommendations for future CRP studies. Overall, this review underscores the potential of CRP as a promising biomarker for managing COVID-19 and highlights the necessity of further research to understand its clinical significance thoroughly.

HMGB1 (high mobility group box 1 protein) refers to a chromatin-associated protein localized in the cytosol to be secreted to the extracellular milieu from multiple cell types including immune and non-immune cells. In this context, HMGB1 functions as a proinflammatory cytokine. Microglia as the main resident immune cells in the brain actively express and secrete HMGB1. Accumulative evidence suggests that HMGB1, released not only by microglia but also astrocytes and endothelial cells, plays a central role in mediating inflammatory signaling and driving the progression of neuroinflammation. In this review, we aim to discuss the critical role and key implications of HMGB1 in neuroinflammation, focusing on the most recent studies and discoveries in this area.

Objective: The overexpression of aurora a kinase is associated with leukaemia as it is an essential regulator of mitotic progression, rendering it a promising therapeutic target. This study employed a multi-step in silico strategy that incorporated computational screening, molecular docking, Density Functional Theory (DFT) analysis, free energy calculations (MM-GBSA), and Molecular Dynamics (MD) simulations to evaluate the potential of natural compounds as Aurora A kinase inhibitors. Methods: An initial virtual screening of 3,093 natural compounds from the Selleckchem library was performed. Drug-likeness was assessed using Lipinski’s Rule of Five, which filters compounds based on key pharmacokinetic parameters: molecular weight (≤ 500 Da), LogP (≤ 5), hydrogen bond donors (≤ 5), and hydrogen bond acceptors (≤ 10). A total of 2,045 compounds that satisfied all these criteria were selected for further analysis and bioactivity evaluation. Results: After ML-based QSAR screening, molecular docking identified 683 ligands with binding affinities of ≤-6.0 kcal/mol. Out of all natural compounds, PubChem CID: 94381 (Coumarin 7) and PubChem CID: 1830 (7-Iodo-7-deaza-D-guanosine) showed minimal RMSD (0.1-0.3 nm), and high hydrogen bonding (2-6 stable contacts) during the 100 ns MD simulations, suggesting stable binding within the aurora A kinase active site. The strong binding affinity of MM-GBSA was further validated by the binding free energy calculations, which showed favourable values of ΔG =-27.93 kcal/mol (94381) and -27.50 kcal/mol (1830). Conclusion: Further, with a dipole moment of 2.80 D, 1830 had great electrical stability, and the lowest HOMO-LUMO gap (-0.1580 eV/-0.1311 eV) was observed in 94381, according to DFT calculations, which indicated significant reactivity. Additionally, synthetic accessibility scores of 3.19 and 4.00, respectively, and iLOGP (integrative octanol–water partition coefficient) values of 2.46 (94381) and 1.57 (1830), both compounds showed ideal drug-like characteristics and may be developed further.

Sirtuin 1 (SIRT1) is a NAD ⁺ ‐dependent deacetylase belonging to the sirtuin family, which regulates a broad spectrum of cellular processes through deacetylation of both histones in the nucleus and non‐histone proteins in the cytosol. Accumulating evidence indicates that biological aging is associated with a marked decline in the expression and activation of SIRT1 /SIRT1, which contributes to the onset and progression of various age‐related diseases. Conversely, activation of SIRT1 has been shown to mitigate aging‐associated cellular anomalies including mitochondrial dysfunction, oxidative stress, and cellular senescence. In this review, we summarize recent advances in understanding the role of SIRT1 in aging and age‐associated diseases across various experimental models, and we also discuss current limitations in the field as well as potential future research direction.

Sirt1 (sirtuin 1) is a member of the sirtuin family of NAD⁺‐dependent histone deacetylases, which mediates the deacetylation of both histone and nonhistone protein substrates, including enzymes and transcription factors. Through this process, Sirt1 regulates gene transcription and activates various cellular functions. FOXO1 (forkhead box protein O1), a key substrate of sirt1, is a transcription factor that controls the expression of genes involved in a wide range of cellular processes. In the context of cancer, the activation of the sirt1–FOXO1 signaling pathway is influenced by various molecular mechanisms, leading to complex and often contradictory outcomes. Depending on the type of malignancy and experimental cell model, this pathway can either promote or inhibit tumorigenesis, cancer progression, drug resistance, and tumor growth. In this perspective, we aim to explore the mechanisms underlying Sirt1–FOXO1 signaling in cancer pathophysiology, tumorigenesis, and drug resistance. We will provide an in‐depth discussion of the current in vitro and in vivo data, hoping to shed light on potential new research directions and to contribute to the development of therapeutic strategies, pending further investigation.

It is reported that according to WHO report (2020), more than 229 million people in 87 countries have malaria despite the use of antimalarial drugs. Moreover, modern combination therapy cannot exclude this disease either. The fact is that malaria pathogens, as well as pathogens of other infectious diseases, gradually acquire resistance to anti-infective drugs. And such resistance of parasites to antimalarial drugs increases with increasing duration of use of these drugs in the community. In other words, antimalarial drugs used in the treatment and prevention of malaria are not only factors in the treatment and prevention of malaria, but gradually acquire the role of factors affecting the “natural” selection of pathogens. It is with the help of applied antimalarial drugs that parasites gradually adapt to existence in the organism of malaria patients, trying to survive despite the availability of drugs. It is shown that the intensity of mutations of malaria pathogens in their population, parasite load, choice of antimalarial drugs, accounting and control of antimalarial activity of the drugs used, the effectiveness and safety of the drugs used, their single and course doses, the effectiveness of individual course antimalarial therapy and control of drug-parasite interaction are the main factors in the effectiveness of treatment and prevention of malaria, as well as the factors of drug resistance of parasites. The review reiterates the importance of knowledge of the basic metabolism and life cycle of both parasite and host in understanding the mechanism of drug action and drug resistance in parasites. This knowledge is very important for the selection of new drug targets for the search and development of new antimalarial drugs. It is reported that fever, diurnal rhythm of body temperature, and therapeutic hyperthermia are not only factors in preventing infection, keeping patients healthy, and the course of malaria, but also factors in the mechanism of action of antimalarial drugs, the efficacy of drug therapy for infection, and the resistance of malaria pathogens to antimalarial drugs.