Mustansiriyah University

Despite optimal lipid-lowering treatment, numerous older adults with atherosclerotic cardiovascular disease continue to experience progression driven by inflammation, referred to as residual inflammatory risk. Cellular senescence and the senescence-associated secretory phenotype (SASP) significantly contribute to vascular inflammaging; however, pharmacological interventions in aging populations are still inadequately investigated. This review synthesizes evidence regarding the role of SASP in atherosclerosis and critically evaluates senotherapeutic strategies, emphasizing mechanisms, preclinical efficacy, and translational potential. Senescent endothelial cells, vascular smooth muscle cells, and foam cells aggregate in plaques, secreting pro-inflammatory cytokines (IL-1α, IL-6, MCP-1) and matrix metalloproteinases that enhance plaque susceptibility. Two complementary pharmacological strategies have emerged. Senolytics (dasatinib combined with quercetin, fisetin, and lanatoside C) specifically eradicate senescent cells by inhibiting anti-apoptotic pathways (BCL-2, PI3K/AKT, and HSP90). Senomorphics (rapamycin, metformin, JAK/STAT inhibitors, NF-κB inhibitors) attenuate SASP expression through modulation of mTOR, NF-κB, and JAK/STAT pathways. Preclinical studies indicate that senolytics diminish the burden of senescent cells, reduce plaque area, and limit necrotic core expansion, while simultaneously improving plaque stability. Senomorphics provide comparable advantages with profiles appropriate for prolonged utilization. Targeting SASP constitutes a rational strategy to alleviate residual inflammatory risk. Nonetheless, significant knowledge deficiencies persist concerning patient selection, dosing protocols, drug-drug interactions with cardiovascular treatments, and long-term safety. Translation necessitates stringent clinical trials in geriatric cardiovascular patients. This review offers an extensive pharmacological framework for senotherapeutics in atherosclerosis.

Gestational trophoblastic neoplasia (GTN) includes a unique group of human neoplastic diseases that derive from fetal trophoblastic tissues. Choriocarcinoma is the most aggressive type of GTN, and patients tend to develop early systemic metastases. It can be either gestational or non-gestational in origin. Although most patients with gestational trophoblastic neoplasia are cured by chemotherapy and tumor resection, some patients suffer from metastatic diseases that are refractory to conventional chemotherapy. Therefore, new therapeutic regimens are needed to reduce the toxic effects associated with current chemotherapy and to salvage the occasional non-operable patients with recurrent and chemo-resistant disease. Until the fundamental biology of gestational trophoblastic neoplasia becomes more clearly understood, development of a new treatment will remain empirical. It has been shown that the antidiabetic metformin, by its antiproliferative effect, can reduce the proliferation and metastasis of choriocarcinoma. However, the fundamental cellular and molecular mechanisms of metformin in treating gestational choriocarcinoma are not fully elucidated. Therefore, this review will briefly summarize the recent advances in understanding the molecular mechanisms of metformin in gestational choriocarcinoma.

Istradefylline, a selective adenosine 2A receptor (A2AR) antagonist, was approved in 2019 as an adjuvant treatment to reduce "OFF" periods in Parkinson's disease (PD) patients. This comprehensive review evaluates its dual impact on PD, contrasting established therapeutic benefits in motor symptom management with emerging concerns regarding cognitive safety. Istradefylline enhances dopaminergic transmission in the substantia nigra pars compacta (SNpc), significantly reducing L-DOPA-induced akinesia. Beyond motor control, it exhibits neuroprotective potential by mitigating neuroinflammation, oxidative stress, and alpha-synuclein-induced neurotoxicity. However, preclinical evidence suggests a concerning paradox: istradefylline may exacerbate cognitive decline by promoting amyloid-beta (Aβ) accumulation through the overactivity of γ-secretase and the disruption of brain-derived neurotrophic factor (BDNF) signaling pathways. Furthermore, its inhibitory effect on D-aspartate protein may trigger mitochondrial dysfunction and endoplasmic reticulum stress, potentially accelerating neurodegeneration in the SNpc. While istradefylline remains a valuable non-dopaminergic strategy for stabilizing motor fluctuations, its influence on long-term cognitive function necessitates careful clinical consideration. Understanding the molecular mechanisms behind these opposing effects is essential for optimizing its use and minimizing neurocognitive risks in PD patients. Future longitudinal trials are vital to clarify its long-term safety profile and disease-modifying potential.

Allergies are a common health issue where the immune system reacts to substances in the environment that are normally harmless. This study further investigates the effects of vascular endothelial growth factor (VEGF), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-38 (IL-38), immunoglobulin E (IgE), and the neutrophil-lymphocyte ratio (NLR) in these individuals, offering insight into the probable processes behind allergic responses following the pandemic. The study comprised 120 non-vaccinated females with previous COVID-19 infection. Groups included controls and food and air (F&A) allergic patients, with 60 individuals matched for age and gender. Serum levels of IL-38, VEGF, IgE, and NGLA were assessed using ELISA kits, while complete blood count (CBC) parameters were analyzed using Coulter LH 750 Hematology Analyzer. Significant differences in biomarkers were found in individuals with F&A compared to controls. F&A patients had decreased white blood cell (WBC) counts but no significant differences in red blood cell count (RBC) or hemoglobin (Hb) count. VEGF and NLR were significantly increased in F&A patients (ppp

Broken heart syndrome (Takotsubo or stress cardiomyopathy) is a transient form of acute left ventricular dysfunction commonly triggered by emotional or physical stress. Despite its reversible nature, it may lead to severe complications such as pulmonary edema, arrhythmias, or cardiac arrest. Current management remains largely supportive, with no established pharmacological therapy. Metformin, a well-known anti-diabetic drug, has emerged as a potential cardioprotective agent due to its multifaceted actions on cellular metabolism, vascular function, and neuro-hormonal balance. By activating the AMP-activated protein kinase (AMPK) pathway, Metformin improves microvascular perfusion, enhances endothelial nitric oxide bioavailability, and inhibits oxidative stress and NLRP3 inflammasome activation, thereby reducing myocardial inflammation and injury. It also restores the adiponectin/leptin ratio, attenuates macrophage polarization, and modulates the PI3K/AKT/mTOR signaling cascade, thereby preserving mitochondrial function and cardiomyocyte viability. Furthermore, metformin contributes to stabilization of the autonomic and brain–heart axes by mitigating catecholamine-driven sympathetic surges and monoamine oxidase-mediated oxidative damage. Collectively, these mechanisms suggest that Metformin may have significant cardioprotective potential in broken heart syndrome by targeting endothelial dysfunction, neurogenic stress, and inflammatory responses, warranting further preclinical and clinical investigation to validate its therapeutic role. Proposed mechanisms of Metformin in mitigating broken heart syndrome under hyperglycemic conditions. Hyperglycemia contributes to sympathetic overactivity, promoting excessive catecholamine release, coronary vasospasm, and endothelial dysfunction, all of which culminate in broken heart syndrome. Metformin exerts protective effects through multiple mechanisms: it improves coronary microcirculation by enhancing microvascular perfusion, reducing oxidative stress, and alleviating peri-coronary inflammation; restores autonomic regulation by normalizing catecholamine levels and improving brain-heart axis function; and modulates key signaling pathways, including suppression of the PI3K/AKT/mTOR and NLRP3 inflammasome cascades via AMPK-dependent mechanisms. (Created with BioRender.com).