Targets, Volume 3, Issue 2 (June 2025) – 11 articles

In West Africa, Paullinia pinnata (P. pinnata) alcohol leaf extracts are used to treat disorders such as depression and anxiety with no documented scientific justification. We have therefore evaluated the potential anxiolytic and antidepressant effects of Paullinia pinnata methanol leaf extract (PPME) in mice, along with probable underlying mechanisms. Adult Swiss albino mice were administered 100, 200, and 400 mg/kg of PPME orally before subjecting them through elevated plus maze (EPM) and hole-board tests to assess the anxiolytic effect. The tail suspension test (TST) and the forced swim test (FST) were used to assess the antidepressant-like effects. Reserpine, labetalol, and risperidone were used to investigate probable mechanisms of action. In both FST and TST, the duration of immobility was considerably reduced by PPME. Conversely, PPME had no significant effect on the number of mice who dipped their heads into the hole-board or entered the EPM’s open arm. Mechanistic analysis revealed that in mice given labetalol or risperidone beforehand, PPME dramatically reduced the length of immobility and reversed ptosis and akinesia caused by reserpine. Our findings suggest that PPME possesses antidepressant-like, but not anxiolytic-like, effects in mice, and antidepressant action may involve enhancing noradrenergic and serotonergic mechanisms. Full article

Gastrointestinal metastases of malignant melanoma are relatively common and pose significant challenges to clinical management due to their complex presentation and resistance to therapy. Early detection and a multidisciplinary treatment approach are critical to improve outcomes. This review highlights targeted treatment strategies for gastrointestinal melanoma metastases, focusing on current therapeutic options and the mechanisms underlying drug resistance. Advances in immune checkpoint inhibitors (ICIs) and targeted therapies, such as BRAF and MEK inhibitors, have revolutionized melanoma treatment, yet their efficacy is often limited by the emergence of resistance mechanisms, including genetic mutations, tumor microenvironment factors, and immune escape. Herein, we explore potential resistance biomarkers for resistance and emerging targeting treatments targeting these pathways. Understanding the molecular and cellular mechanisms driving drug resistance remains critical to overcoming therapeutic limitations, emphasizing the importance of collaborative efforts in research and clinical practice to refine therapeutic approaches and improve survival rates for patients with metastatic melanoma involving the gastrointestinal tract. Future directions include optimizing combination therapies and leveraging precision medicine to address resistance and disease progression. Full article

Non-small-cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide with only approximately 30% of new diagnoses manifesting with localized stages IA–IIA. Osimertinib is a third-generation inhibitor of the epidermal growth factor receptor (EGFR), which is used for treating metastatic, locally advanced, and early-stage NSCLC expressing common EGFR mutations. Two phase III clinical trials supported yresectable locally advanced disease, consisting of the ADAURA and LAURA studies, respectively. On the other hand, conflicting data on neoadjuvant efficacy led to the design of the ongoing Neo-ADAURA trial. In this review, we describe the pivotal trials that led to the approval of osimertinib use as an adjuvant treatment in radically resected NSCLC patients and as maintenance therapy after chemoradiotherapy. We also summarize the principal ongoing clinical trials in the neoadjuvant and adjuvant settings. Finally, we analyze several issues about the use of osimertinib in those different early settings while also depicting future perspectives and the potential evolution of treatment strategies. Full article

Pharmacological relevance: Ethnic people residing in the Chittagong Hill Tracts (CHTs) of Bangladesh use Pouzolzia sanguinea to alleviate flatulence, for menstruation, inflammation, insomnia, and analgesia. However, there is no scientific evidence regarding the bioactivity of these plants. Aim: This study aimed to isolate bioactive fractional compounds from Pouzolzia sanguinea (IFCPS) crude extract to assess the anti-inflammatory, analgesic, and anxiolytic activities. Materials and Methods: Preparative TLC-bioautography and silica gel two-stage column chromatography were used to isolate bioactive fractional compounds from P. sanguinea methanol crude extracts. The anti-inflammatory, analgesic, and anxiolytic activities of extracts and IFCPS were studied by inhibiting protein denaturation, acetic acid-induced writhing, Eddy’s hot plate, field cross, and hole cross methods. Results: The dried crude extract’s chemical analysis revealed alkaloids, flavonoids, terpenoids, saponins, vitamin C, and tannins. Nine single isolated fractional compounds (IFC₁PS to IFC₉PS) were isolated through TLC. Among these, IFC₂PS exhibited (p ˂ 0.01) the most potent anti-inflammatory activity in the inhibition of protein denaturation studies (70.51%), which was slightly lower than acetyl salicylic acid (82.29%), at160 µg/mL. This inhibitory effect occurred in a dose-dependent manner. IFC₂PS exhibited the most potent peripheral analgesic and moderate central analgesic effects compared to the standard. In contrast, IFC₁PS showed moderate effects in both areas. IFC₈PS showed superior anxiolytic activities compared to crude extracts and other IFCPS. Conclusions: Out of the nine fractional compounds isolated, the IFC₂PS reduced pain and inflammation, whilst IFC₈PS exhibited anxiolytic activities. This is the first comprehensive study demonstrating the anti-inflammatory, analgesic, and anxiolytic effects of crude extracts and isolated fractional compounds from the whole plant of P. sanguinea, which may have immediate experimental and clinical applications. Full article

The liver is an essential metabolic organ that is involved in energy metabolism, protein synthesis, and detoxification. Many endogenous and exogenous factors can cause liver injury, a complex pathological condition. It poses a serious risk to human health due to its extremely varied clinical manifestations, which range from mild fatty liver to liver fibrosis, cirrhosis, and even hepatocellular carcinoma. Because of their low specificity, lack of real-time monitoring, and invasiveness, traditional diagnostic techniques for liver injury, such as histopathological examination and serological analysis, have inherent limitations. Fluorescent probe technology, which offers high sensitivity, non-invasiveness, and real-time imaging capabilities, has become a potent tool in liver injury research and early diagnosis in recent years. The pathophysiology of liver injuries caused by alcohol, chemicals, drugs, and the immune system is methodically covered in this review, along with new developments in fluorescent probe development for their detection. The focused imaging properties of various fluorescent probes are highlighted, along with their possible uses in drug screening and early liver injury detection. This review attempts to offer theoretical insights to support the optimization of precision diagnostic and therapeutic approaches by summarizing these findings. Full article

Background: Obesity has been defined as a true worldwide “pandemic” by the World Health Organization and represents one of the major public health problems. It is associated with a reduction in life expectancy of about 7–8 years due to related cardiovascular diseases such as arterial hypertension, metabolic syndrome, insulin resistance, type 2 diabetes mellitus, and dyslipidemia. Adipose tissue is not merely a fat storage site but a true endocrine and immunologically active organ that secretes hormones and mediators (adipokines), influencing cardiovascular risk and host physiology. Objective: This review summarizes the current understanding of the role of epicardial adipose tissue (EAT) in cardiovascular disease pathophysiology and discusses its clinical diagnostic and therapeutic implications. Methods: A narrative non-systematic review was conducted focusing on recent literature concerning the biological and clinical aspects of cardiac adipose tissue, with particular emphasis on epicardial adipose tissue. The review examined its gene expression profile, secretory function, and interaction with cardiovascular structures and diseases. Findings: There are different types of adipose tissue, including cardiac adipose tissue, which comprises epicardial and pericardial (or paracardiac) fractions. Epicardial adipose tissue is unique due to its proximity to the heart and a distinct gene expression profile compared to other adipose depots such as visceral and subcutaneous fat. EAT plays a crucial role in the development and progression of cardiovascular diseases with high morbidity and mortality, acting both as a metabolic and inflammatory mediator. Conclusion: Cardiac adipose tissue, particularly EAT, is a key player in cardiometabolic disease. Understanding its pathophysiological role and incorporating imaging tools to evaluate EAT may enhance cardiovascular risk stratification and disease management. Full article

Influenza viruses pose a significant threat to human health, and vaccination remains the most cost-effective and efficient strategy for controlling outbreaks. This review first introduces the molecular characteristics of influenza A virus (IAV) and examines how conserved epitopes contribute to overcoming its high variability, laying the foundation for broadly protective vaccine design. Different vaccine platforms are then categorized and analyzed through representative examples to highlight their research significance and application potential. The discussion further extends to the role of adjuvants in modulating immune responses, with a focus on how their optimization enhances vaccine efficacy. We explore future directions in vaccine design, highlighting the synergistic potential of conserved epitope targeting and adjuvant improvement in advancing the next generation of influenza vaccines. Full article

Background and Clinical Significance: Cystic echinococcosis (CE), also known as hydatid disease, is a zoonosis in whose life cycle humans can be an accidental intermediate host. The liver is the most commonly affected organ, with complications like cyst rupture, hematogenous spread, and infection. Imaging techniques, such as ultrasound, CT, and MRI scans, play a vital role in diagnosing and classifying the disease, facilitating the appropriate therapeutic approach. Treatment options include albendazole for early stage cysts, with more invasive procedures like PAIR, MoCAT, and surgery for advanced cases. This article highlights the importance of imaging modalities in the diagnosis and therapeutic management of CE. Case Presentation: We report a case of a 23-year-old female patient presenting with nausea, fatigue, and loss of appetite to the emergency department, who was diagnosed with a giant echinococcosis lesion. The patient received ultrasound, MR, and CT diagnostics initially. The surveillance included ultrasound and MRI, as well as an anthelmintic therapy, and eventually led to an open resection. Conclusions: This case highlights the importance of imaging modalities in diagnosing and therapeutically managing CE. It explains the key features of each WHO classification stage of the disease for each modality, emphasizing the value of an MRI scan as a possibility for surveillance and a bridge to surgery. Full article

Air pollution, particularly from vehicular emissions, has emerged as a critical environmental health concern, contributing to a global estimated 7 million premature deaths annually. Diesel exhaust, a major component of urban air pollution, contains fine particulate matter and gases that evade respiratory filtration, penetrating deep into the lungs and triggering oxidative stress, inflammation, and immune dysregulation. Epidemiological and in vitro studies have linked diesel exhaust exposure to respiratory diseases such as asthma, chronic obstructive pulmonary disease, pulmonary fibrosis, and lung cancer, with immunological mechanisms playing a central role. Diesel exhaust particles induce oxidative stress, impair macrophage phagocytosis, and skew T-cell polarization toward pro-inflammatory Th2 and Th17 responses, exacerbating chronic inflammation and tissue damage. Despite these insights, significant gaps remain in understanding the precise immunomodulatory pathways and long-term systemic effects of diesel exhaust exposure. While animal models and in vitro studies provide valuable data, they often fail to capture the complexity of human exposure and immune responses. Further research is needed to elucidate the mechanisms underlying diesel exhaust-induced immune dysregulation, particularly in vulnerable populations with pre-existing respiratory conditions. This review focuses on summarizing the current knowledge and identifying gaps that are essential for developing targeted interventions and policies to mitigate the adverse health impacts of diesel exhaust and improve respiratory health outcomes globally. Full article

Glycogen synthase kinase-3 beta (GSK-3β) plays a crucial role in multiple cellular processes and is implicated in different types of cancers and neurological disorders, including Alzheimer’s disease. Despite extensive efforts to develop novel GSK-3β inhibitors, the discovery of potent and selective lead compounds remains a challenge. In this study, we evaluated the GSK-3β inhibitory potential of semisynthetic flavonoid derivatives, which exhibited sub-micromolar activity. To gain further insights, we employed molecular docking, molecular dynamics simulations, and pharmacokinetic profile predictions. The docking studies revealed that the most potent inhibitor, compound 10, establishes key interactions with the ATP-binding site. Molecular dynamics simulations further confirmed that compound 10 maintains stable interactions with GSK-3β throughout the simulation. Additionally, pharmacokinetic predictions identified compound 3 as a promising candidate for Alzheimer’s disease therapy due to its ability to cross the blood–brain barrier. These findings suggest that, within the studied flavonoid derivatives, these compounds (particularly 10 and 3) hold potential as lead compounds for GSK-3β inhibition. The combination of strong enzymatic inhibition, stable binding interactions, and favorable pharmacokinetic properties highlights their promise for further development in cancer and neurodegenerative disease research. Full article

Pure red cell aplasia (PRCA) following major ABO-mismatched allogeneic hematopoietic stem cell transplantation (HSCT) is a challenging complication, affecting 7–10% of patients and significantly impacts quality of life. Despite half of patients showing a resolution within three–six months after HSCT, PRCA might require treatment. Various therapeutic approaches have been investigated, including erythropoietin, plasmapheresis or immunomodulatory therapies (rituximab, bortezomib, corticosteroids, donor lymphocyte infusion (DLI), or the early tapering of immunosuppressive drugs), and TPO-mimetic agents, though responses have generally remained suboptimal. Recently, daratumumab has emerged as a promising, safe, and effective treatment for PRCA, documented by numerous case reports and series. We present a case of PRCA arising in a patient with mixed chimerism following a sibling HSCT for aplastic anemia (AA). In line with the literature, our findings highlight the effectiveness of daratumumab in PRCA from the first dose, although daratumumab administrations were delayed by the onset of infectious complications. Our case supports the earlier introduction of daratumumab in the treatment strategy of PRCA to avoid patient exposure to ineffective therapies that carry risks of increased immunosuppression and infections. Indeed, in our specific case, the early introduction of daratumumab may interrupt the immune hematologic mechanism underlying PRCA, which, in the context of mixed chimerism, could increase the risk of graft failure. Full article