Targets

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

The quantification of endocannabinoids in biological fluids is becoming increasingly popular as an indicator of psychological and physiological function. Numerous methods to quantify the endocannabinoid ligands have been published so far, yet their concentrations and responses often exhibit significant variability across studies. Endocannabinoids regulate and interact with a wide range of biomolecules, causing their concentrations to vary between cohorts of individuals, and sensitivities to them depend on pre-experimental behaviours and activities. Moreover, matrix effects produced by the complex nature of biofluids necessitate rigorous sample preparation techniques, all of which introduce opportunities for both inter- and intra-assay variability. This review aims to address the causes of variability prior to mass spectrometric analysis, including biofluid choice, human variability, sample collection and extraction methods. If these factors are fully considered and standardised methods are introduced, endocannabinoid concentrations may become more reliable, allowing their utility as clinical markers to progress. Full article

Schizophrenia is a severe and complex psychological disorder characterised by psychosis, affecting approximately 20 million people worldwide, with its prevalence on the rise. It is hypothesised to arise from a multifactorial aetiology involving a complex interplay of genetic predisposition and environmental risk factors. The exact cause of schizophrenia remains unknown. There are significant interactions between genetic and environmental factors, making it a condition of great significance. Both pharmacological and non-pharmacological therapies are available to manage the various symptoms associated with this condition. Antipsychotic drugs are the primary pharmacological approach, addressing both the positive and negative symptoms of schizophrenia. However, their use has sparked controversies due to potential side effects and long-term consequences, necessitating individualised treatment plans. Non-pharmacological therapies, on the other hand, provide an alternative approach, focusing on reducing anxiety and fear and empowering patients to regain control over their lives. In this scientific review, an extensive analysis of existing research has been conducted to evaluate the efficacy and safety of antipsychotic drugs and non-pharmacological therapies for schizophrenia. Their impact on positive and negative symptoms as well as socio-economic implications have been assessed. Beyond treatment efficacy, this review also addresses broader societal aspects, emphasising the need for patient-centred mental healthcare services that consider individual differences and preferences. The review highlights the importance of a multidimensional translational approach to schizophrenia management and advocates for accessible mental healthcare services to cater to the unique challenges faced by individuals with schizophrenia. By considering advantages and disadvantages, we support the implementation of tailored treatment plans to optimise patient outcomes and overall societal well-being. A holistic translational approach to schizophrenia management, incorporating medical, psychological, and societal support systems is essential for improving the quality of life for individuals living with schizophrenia. Full article

Cornea vascularisation is a significant cause of ocular morbidity. Disease or injury often triggers the development of new blood vessels in the cornea, compromising its clarity and impairing vision. Common causes of corneal neovascularisation include infections, chemical burns, and local and systemic inflammatory disorders. Topical corticosteroid eye drops remain the standard therapy; however, extended use of corticosteroids has been known to cause side-effects including cataracts and raised intraocular pressure. As such, an alternative therapy has been actively sought. Vascular endothelial growth factor (VEGF) is a major angiogenic factor implicated in neovascularisation. The success of anti-VEGF agents in managing leaking blood vessels in neovascular age-related macular degeneration provides an opportunity to explore its use in the treatment of corneal neovascularisation. The therapeutic potential of anti-VEGF agents has been evaluated in experimental models of corneal neovascularisation and clinical trials with variable results. Here, we review the study results and discuss the development of new strategies that may improve treatment outcomes for corneal neovascularisation. Full article

Proteases play a pivotal role in cancer progression, facilitating processes such as extracellular matrix degradation, angiogenesis, and metastasis. Consequently, protease inhibitors have emerged as promising therapeutic agents in oncology. This review provides a comprehensive overview of the mechanisms by which protease inhibitors modulate cancer biology, categorizing inhibitors by their target protease classes, including matrix metalloproteinases, cysteine proteases, and serine proteases. We discuss the therapeutic potential of both synthetic and natural protease inhibitors, highlighting their applications in preclinical and clinical settings. Furthermore, challenges such as specificity, toxicity, and resistance mechanisms are addressed, alongside strategies to overcome these limitations through innovative drug designs and combination therapies. The future of protease inhibitors in cancer treatment lies in precision medicine, leveraging proteomic profiling to tailor therapies to individual tumors. This review underscores the importance of ongoing research and the development of novel approaches to harness protease inhibitors effectively for cancer management. Full article

Bombesin receptor subtype-3 (BRS-3) is a type 1 G-protein-coupled receptor (GPCR). BRS-3 is an orphan GPCR that is structurally related to neuromedin B and gastrin-releasing peptide receptors. When activated, BRS-3 causes phosphatidylinositol turnover in lung cancer cells. BRS-3 stimulates tyrosine the phosphorylation of the epidermal growth-factor receptor (ErbB1); however, it is unknown whether it transactivates ErbB2/HER2. Adding the nonpeptide BRS-3 allosteric agonist MK-5046 or the peptide agonist BA1 to the lung cancer cell line NCI-H727 or to BRS-3-transfected NCI-H1299 lung cancer cells increased the tyrosine phosphorylation of HER2/ERK2. This increase was antagonized by the BRS-3 peptide antagonist Bantag-1 and the small-molecule BRS-3 antagonist ML-18. The increase in HER2/ERK phosphorylation caused by MK-5046 was inhibited by the ROS inhibitors N-acetylcysteine and Tiron (superoxide scavengers). Adding MK-5046 to lung cancer cells increased reactive oxygen species, which was inhibited by NAC or Tiron. MK-5046 and BA1 increased non-small lung cancer cell (NSCLC) colony formation, whereas Bantag-1/ML-18 inhibited proliferation. These results indicate that in lung cancer cells, the activation of BRS-3 regulates HER2 transactivation in an ROS-dependent manner, which can mediate tumor growth. These results raise the possibility that the use of HER2-inhibiting compounds alone or in combination with other agents could represent a novel approach to the treatment of these tumors. Full article

Many health benefits are associated with Vitamin D (VitD), although deficiency is associated with poor health outcomes and the increased risk of cancer development. For example, many tissue-specific enzymes are involved in VitD metabolism, and mutations or deletions within Vitamin D receptor (VDR) genes are known to increase the cancer risk by altering their functions or bioavailability, although less is known about these phenomena in oral cancers. Using well-characterized, commercially available oral cell lines (OKF4, HGF-1, SCC4, SCC9, SCC15, SCC25, and CAL27), the mRNA expression of P450 cytochrome VitD metabolic enzymes and receptor genes by qPCR revealed differential results. One oral cancer line (SCC15) did not express either the Vitamin D receptor (VDR) or FOK1 polymorphism and was also least affected by VitD3 administration in growth assays. In contrast, most oral cancers were missing one or more hydrolase (CYP2R1 and CYP24A1) or hydrolate (CYP27A1 and CYP27B1) enzymes. SCC25 was missing both the hydrolate enzymes and was the most inhibited in the VitD3 growth assays, while SCC4 was missing both the hydroxylase enzymes and was the least inhibited by VitD2. These associations between mRNA expression (or lack thereof) and VitD3 and VitD2 responsiveness can be used to identify molecular targets, which may lead to effective screening tools for VitD-related, complementary and alternative therapies. Full article

The fibroblast growth factor (FGF) family includes 22 proteins in humans. Based on their mode of action, there are three families of FGFs: paracrine FGFs (FGF 1–10, 16, 17, 18, 20, and 22), intracrine FGFs (FGF 11–14), and endocrine FGFs (FGF 19, 21, and 23). FGF signaling plays critical roles in embryonic development, tissue repair, regeneration, angiogenesis, and metabolic regulation. They exert their cellular functions by binding, dimerization, and activation of transmembrane FGF receptors (FGFRs). Aberrant FGF signaling is associated with various human diseases. Thus, understanding the unique properties of FGF signaling will help to explore new therapeutic interventions against FGF-mediated pathological conditions. This review will discuss the differential expression and regulation of each FGF under normal human physiological and pathological conditions. Moreover, we will outline current therapeutics and treatment strategies that have been developed against FGF-related pathology. Full article

Colorectal cancer (CRC) is one of the major reasons for cancer-related deaths around the world. Constitutive activation of WNT pathway, due to APC gene mutation, is the characteristic feature of most human colon tumors. Familial adenomatous polyposis (FAP) patients inherit APC mutations and pose an absolute risk of developing CRC in their lifetime. The genetically modified APC mouse models have paved the way to study various aspects of the hereditary human CRC, including biochemical, molecular, and histological aspects. Preclinical and clinical data suggest that certain dietary supplements, NSAIDs, natural products, and chemically synthesized compounds, can help in intercepting CRC incidence and progression by modulating various hallmarks of cancer. In this review, we have provided a summary of promising natural and synthetic agents that demonstrated chemopreventive efficacy against CRC in the FAP-mimicking APC^Min/+ mouse model. Full article

We recently found that myometrial distension stimulates maternal uterine vascular remodeling, and hypothesized that this may be a previously unrecognized mechanism for inducing arterial growth during pregnancy. The aim of this study was to further characterize a recently developed surgical model in which medical-grade silicone was infused into one uterine horn of a non-gravid rat to induce acute myometrial stretch, followed by an additional, gradual distension due to the secretion of an exudate into the uterine lumen. Our objectives were to better understand the effects of stretch on the myometrium and to look for the expression of proangiogenic and proinflammatory factors that may stimulate uterine vascular remodeling. Morphometric analysis showed hypertrophy of the uterine corpus that was primarily due to axial growth since the myometrial cross-sectional area was unchanged due to a thinning of the uterine wall secondary to stretch. This finding was supported by significantly increased myometrial smooth muscle cell mitosis. There was also an increase in the concentration of myometrial elastin but not collagen. The analysis showed modest increases in neutrophils, activated and unactivated macrophages, and the proinflammatory cytokines RANTES, MIP-3α, GRO-KC, and TNFα. The most dramatic change was the extremely high level of VEGF in the exudate, which was increased >900× above circulating levels. Full article

In recent years, machine learning algorithms have seen extensive application in chemical science, especially in cell detection technologies. Machine learning, a branch of artificial intelligence, is designed to automatically discover patterns in data. This review provides an overview of cell detection methods such as bright-field microscopy (BL), dark-field microscopy (DL), surface-enhanced Raman scattering (SERS), and fluorescence detection (FL). We highlight key computational models like support vector machines and convolutional neural networks that significantly enhance the precision and efficiency of automated cell detection. Relevant research applications are discussed, along with future prospects for machine learning in cell analysis. Full article

Aromatic properties of two series of quinoline derivatives were studied theoretically using the Density Functional Theory (DFT) approach. One series of compounds possesses antimalarial activity while the other does not have such properties. The B3LYP functional and the 6-311++G** basis set were employed in the study. The optimized geometries of the studied compounds were used for aromaticity level determination using several aromaticity indices, like HOMA, NICS, PDI, I₆, FLU, and PLR. It was shown that the level of aromaticity seems to be a feature that differentiates these two series of compounds. This is reasonable because it has been presented, previously in the literature, that this type of drug acts as an antimalarial drug through the formation of the π-π complex with ferriprotoporphyrin. There are two types of rings in the quinoline system, a benzene type, and a pyridine type. The aromaticity of the benzene-type ring in both series of studied compounds is similar while the aromaticity of the pyridine-type ring is lower for compounds that have antimalarial properties. It is derived on the basis of performed research that the properties of the pyridine-type ring are more important for the drug activity of studied compounds. Full article

Head and neck cancer (HNC) is the seventh most commonly diagnosed malignancy worldwide, and its incidence is expected to increase in coming years. Current diagnostic methods for HNC are often limited by suboptimal accuracy and speed, which can negatively impact therapeutic decision-making and patient outcomes. To address the shortcomings of conventional diagnostics, biomarker detection has attracted increasing clinical interest as a promising alternative. However, a major challenge is the identification of biomarkers with sufficient accuracy and sensitivity for HNC. The integration of bioinformatics tools with omics data analysis has proven to be a robust approach for biomarker discovery. In this study, we outline a bioinformatics protocol aimed at identifying differentially expressed genes (DEGs) in HNC and evaluating the diagnostic and prognostic relevance of specific genes, including FN1, LGALS3, MMP9, TIMP1, MMP2, and TIMP2, in this pathology. In addition, we performed an enrichment analysis for the genes of interest. The prognostic significance of the selected genes was evaluated in relation to patient survival. This study contributes to the growing body of knowledge by identifying potential biomarkers with diagnostic and prognostic utility in this malignancy. Full article

Alzheimer’s disease is a neurodegenerative disease that continues to have a rising number of cases. While extensive research has been conducted on Alzheimer’s disease in the last few decades, only a few drugs have been approved by the FDA for its treatment, and even fewer aim to be curative rather than manage symptoms. There remains an urgent need to understand disease pathogenesis, as well as identify new targets for further drug discovery. Alzheimer’s disease (AD) is known to stem from the build-up of amyloid beta (Aβ) plaques, as well as tangles of tau proteins. Furthermore, inflammation in the brain is known to arise from the degeneration of tissue and the build-up of insoluble material. Therefore, there is a potential link between the pathology of AD and inflammation in the brain, especially as the disease progresses to later stages, where neuronal death and degeneration levels are higher. Proteins that are relevant to both brain inflammation and AD, thus, make ideal potential targets for therapeutics; however, the proteins need to be evaluated to determine which targets would be ideal for potential drug therapeutic treatments, or ‘druggable’ targets. Druggability analysis was conducted using two structure-based methods (i.e., drug-like density analysis and SiteMap), as well as a sequence-based approach, SPIDER. The most druggable targets were then evaluated using single-nucleus sequencing data for their clinical relevance to inflammation in AD. For each of the top five targets, small molecule docking was used to evaluate which FDA approved drugs were able to bind with the chosen proteins. The top targets included DRD2 (inhibits adenylyl cyclase activity), C9 (binds with C5B8 to form the membrane attack complex), C4b (binds with C2a to form C3 convertase), C5AR1 (a GPCR that binds C5a), and GABA-A-R (the GPCR involved in inhibiting neurotransmission). Each target had multiple potential inhibitors from the FDA-approved drug list with decent binding infinities. Among these inhibitors, two drugs were found to be top inhibitors for more than one protein target. They were C15H14N2O2 and v316 (paracetamol), originally used to treat pain/inflammation for cataracts and relieve headaches/fever, respectively. These results provide the groundwork for further experimental investigations or clinical trials. Full article

Pulmonary arterial hypertension (PAH) is a progressive and rare condition characterised by the occlusion of pulmonary arterioles, with clinical manifestations resulting from the cross-sectional area reduction of the small pulmonary arteries. The disease is driven by a combination of factors including vasoconstriction, thrombosis, inflammation, proliferation, and the obstructive remodelling of the pulmonary artery walls. Heterozygous mutations in the type II bone morphogenetic protein receptor (BMPR2) underlie the majority of the inherited and familial forms of PAH. Current evidence indicates that in PAH, the BMPR2-mediated-signalling is diminished and the TGFβ signalling is heightened. Even when managed with current therapeutic approaches, the disease eventually results in increased pulmonary vascular resistance, right heart failure, and premature death. Natural products act as vascular disease treatment agents and have been used in clinical practice following compelling clinical trials. The rationale for the selection of natural compounds derives from their multi-targeted approach and synergistic effects. Although novel medicines licenced by the FDA (USA) between 1981 and 2010, constitute approximately 34% natural products or derivatives of natural products, their potentials for the treatment of PAH are not fully explored. The objective of this review is to emphasise the significance of natural products in the therapeutic resolution of PAH. Full article

This review article explores the current landscape of acute myeloid leukemia treatment, including novel target molecules and recent advancements in cell therapy and immunotherapy focused on T cell activity. Advances in treatment have been promising in recent years, driven by the development of therapies targeting new molecular and genetic therapeutic targets. These findings allowed for the approval of several target therapies by the European and American drug agencies in the last 5 years. However, mortality remains very high, particularly in relapsed or refractory (R/R) patients. In recent years, the development of immunotherapy has expanded this field, leading to the introduction of new drugs and treatments. Full article