Analyzing a higher order q(t)q(t) model and its implications in the late evolution of the Universe using recent observational datasets

In this research paper, we explore a well-motivated parametrization of the time-dependent deceleration parameter, characterized by a cubic form, within the context of late time cosmic acceleration. The current analysis is based on the $f(Q,T)$ gravity theory, by considering the background metric as the homogeneous and isotropic Friedmann Lema\^itre Robertson Walker (FLRW) metric. Investigating the model reveals intriguing features of the late universe. To constrain the model, we use the recent observational datasets, including cosmic chronometer (CC), Supernovae (SNIa), Baryon Acoustic Oscillation (BAO), Cosmic Microwave Background Radiation (CMB), Gamma Ray Burst (GRB), and Quasar (Q) datasets. The joint analysis of these datasets results in tighter constraints for the model parameters, enabling us to discuss both the physical and geometrical aspects of the model. Moreover, we determine the present values of the deceleration parameter ($q_0$), the Hubble parameter ($H_0$), and the transition redshift ($z_t$) from deceleration to acceleration ensuring consistency with some recent results of Planck 2018. Our statistical analysis yields highly improved results, surpassing those obtained in previous investigations. Overall, this study presents valuable insights into the higher order $q(t)$ model and its implications for late-time cosmic acceleration, shedding light on the nature of the late universe

Targeting eosinophils in respiratory diseases: Biological axis, emerging therapeutics and treatment modalities

Eosinophils are bi-lobed, multi-functional innate immune cells with diverse cell surface receptors that regulate local immune and inflammatory responses. Several inflammatory and infectious diseases are triggered with their build up in the blood and tissues. The mobilization of eosinophils into the lungs is regulated by a cascade of processes guided by Th2 cytokine generating T-cells. Recruitment of eosinophils essentially leads to a characteristic immune response followed by airway hyperresponsiveness and remodeling, which are hallmarks of chronic respiratory diseases. By analysing the dynamic interactions of eosinophils with their extracellular environment, which also involve signaling molecules and tissues, various therapies have been invented and developed to target respiratory diseases. Having entered clinical testing, several eosinophil targeting therapeutic agents have shown much promise and have further bridged the gap between theory and practice. Moreover, researchers now have a clearer understanding of the roles and mechanisms of eosinophils. These factors have successfully assisted molecular biologists to block specific pathways in the growth, migration and activation of eosinophils. The primary purpose of this review is to provide an overview of the eosinophil biology with a special emphasis on potential pharmacotherapeutic targets. The review also summarizes promising eosinophil-targeting agents, along with their mechanisms and rationale for use, including those in developmental pipeline, in clinical trials, or approved for other respiratory disorders

Clinical efficacy and safety of angiogenesis inhibitors: sex differences and current challenges

Vasoactive molecules, such as vascular endothelial growth factor (VEGF) and endothelins, share cytokine-like activities and regulate endothelial cell (EC) growth, migration and inflammation. Some endothelial mediators and their receptors are targets for currently approved angiogenesis inhibitors, drugs that are either monoclonal antibodies raised towards VEGF, or inhibitors of vascular receptor protein kinases and signaling pathways. Pharmacological interference with the protective functions of ECs results in a similar spectrum of adverse effects. Clinically, the most common side effects of VEGF signaling pathway inhibition include an increase in arterial pressure, left ventricular (LV) dysfunction ultimately causing heart failure, and thromboembolic events, including pulmonary embolism, stroke, and myocardial infarction. Sex steroids such as androgens, progestins, and estrogen and their receptors (ERα, ERβ, GPER; PR-A, PR-B; AR) have been identified as important modifiers of angiogenesis, and sex differences have been reported for anti-angiogenic drugs. This review article discusses the current challenges clinicians are facing with regard to angiogenesis inhibitor treatments, including the need to consider sex differences affecting clinical efficacy and safety. We also propose areas for future research taking into account the role of sex hormone receptors and sex chromosomes. Development of new sex-specific drugs with improved target and cell-type selectivity likely will open the way personalized medicine in men and women requiring antiangiogenic therapy and result in reduced adverse effects and improved therapeutic efficacy