Precision cancer therapies frequently fail due to tumors’ evolving clonal diversity rather than drug efficacy. Even when initial treatment succeeds, resistance often emerges, leading to relapse. Clinicians then find themselves in the same cycle of repeating the process of testing a new drug until therapeutic exhaustion. The cycle escalates with each new treatment until no further options are available. The real-life experience of precision therapy will undeniably lead to an upgrade - from biomarker testing to drug response prediction - accordingly to favor more effective treatment options, more clinical benefit, and more patient coverage to include non-responders. While biomarker tests (or companion diagnostics) advance precision medicine by identifying only a fraction of patients as responders, drug response prediction aims to expand treatment options - particularly for non-responders - by tailoring personalized therapies to optimize outcomes while minimizing side effects. Artificial intelligence-driven approaches (e.g., deep learning and predictive modeling) leverage large datasets to generate these predictions. However, such systems remain experimental, not yet ready for clinical use. Patient-derived gene expression-informed anticancer drug efficacy (PGA) is the ultimate answer to the unmet clinical need for a quick turnaround and cost-efficient drug response prediction technology. With PGA, therapeutic non-responders now are able to benefit from more drug options than ever before. Since the technology is fitted with patient testing, gene activity detection, data mapping, drug matching, and efficacy ranking capabilities, clinicians can be quickly notified of potentially effective drugs, winning the decisive time for decision-making.

Pancreatic cancer (PC) remains one of the most lethal forms of cancer. Unfortunately, existing drugs for PC would cause significant side effects, and the tumor may develop resistance to these treatments. Therefore, there is an urgent need to develop new drugs to provide more treatment options for PC patients. Compared to traditional protein-targeted and DNA-based drugs, ribonucleic acid (RNA)-based therapies have gained significant attention in recent years due to their unique physicochemical and physiological properties. Various strategies have been developed to enhance the metabolic stability and intracellular delivery of small RNA drugs, making them a key focus in cancer drug development in recent years. To explore the therapeutic potential of small RNA drugs in PC, an overview of the status of small RNA drug development is provided, including 17 approved small RNA drugs and 43 small RNA drug candidates in clinical trials. In addition, genetic factors involved in PC progression are examined, identifying 17 protein-coding genes and 15 microRNA genes. Finally, six strategies for developing small RNA drugs for PC are discussed.

The advancement of nanotechnology in the biomedical field has garnered growing interest due to the diverse physical properties of nanoparticles (NPs) and their potential applications in cancer theranostics. Although various nanodrug delivery systems, such as polymeric, lipid-based, and gold NPs, are available, superparamagnetic iron oxide NPs (SPIONs) have attracted significant attention due to their multifunctionality, biocompatibility, ease of surface functionalization, and responsiveness to external magnetic fields, enabling both cancer diagnostics and drug delivery applications. This review provides an overview of SPIONs as a powerful theranostic tool in cancer treatment. It also focuses on the synthesis and stabilization of SPIONs, discussing various protection and stabilization strategies using both organic coatings (synthetic and natural polymers) and inorganic coatings (such as silica and gold), as well as liposomes. In addition, the review highlights targeted biomedical applications of SPIONs, including magnetic resonance imaging, hyperthermia, and drug delivery. Finally, it also addresses the challenges and limitations of SPIONs, as well as their future perspective in clinical translation in cancer theranostics.

One of the greatest challenges faced by precision medicine is the identification of biomarkers capable of detecting clinically meaningful change at the individual level, not just among large-scale population studies. To this end, the high-volume nature of an individual’s social media data could be leveraged with single-user precision to monitor sleep patterns and tweet content to determine emotional state. However, there is a lack of established methods to detect and estimate sleep and mood using social-media activity. We present here a new approach (digital rest-activity rhythms analysis) to using social media to track both sleep and mood, with potential applications to mental health monitoring and prevention. Our proof-of-concept showed that the emotional content of a single user’s tweets (Kanye West “@Ye”) were influenced by sleep disturbances inferred from usage over a 2-year period. We herein provide an ethical and theoretical-framework of how to proceed among this sensitive yet potentially fruitful field.

Atherogenic plasma lipid and glycemic profiles are commonly observed in obesity and adult-onset type 2 diabetes mellitus (T2DM) and may improve following therapeutic intervention. The effects of the luminal α-glucosidase inhibitor miglitol (MIG) on carbohydrate digestion and plasma lipid profiles were evaluated in adult male obese spontaneously hypertensive and diabetes-prone/Ntul//-cp rats, a genetic model that develops early-onset obesity and T2DM independently of diet. Rats were fed either a nutritionally complete diet (formulated by the United States Department of Agriculture) containing 54% sucrose as the carbohydrate component (control) or the same diet supplemented with MIG at 150 mg/kg of diet admixture ad libitum for <8 weeks. MIG treatment resulted in a ~15% decrease in energy intake (p<0.05), net weight gain (p<0.05), and a 14% decrease in adiposity (p<0.05), along with significant decreases in fasting glucose, insulin, and glycated hemoglobin (p<0.05). In addition, MIG reduced the glucose area under the curve by 20% (p<0.05), triglycerides by 15% (p<0.05), and the total cholesterol, α-lipoprotein (low-density lipoprotein), and β-lipoprotein (high-density lipoprotein) fractions by 20% (p<0.05, all comparisons). MIG regimen also led to decreases in liver glucokinase, malic enzyme, and glucose-6-phosphate dehydrogenase (p<0.05). In conclusion, these results suggest that therapeutic α-glucosidase inhibition through MIG improves multiple insulin-related atherogenic parameters and may serve as a useful adjunct in the long-term clinical management of plasma lipid and glycemic profiles in the glucose-intolerant states of obesity and T2DM.

Liver steatosis is a common cause of chronic liver disease. To investigate the molecular basis of hepatic steatosis, low-density lipoprotein receptor-deficient (LDLR -/-) mice were fed a Western diet (WD, 42% of calories from fat) for 5, 14, or 42 days and evaluated against mice fed a normal laboratory diet. Histological analyses revealed that steatosis was detected as early as 14 days of WD feeding. Bulk RNA sequencing demonstrated that WD feeding altered liver transcriptomes related to inflammation and cell adhesion consistent with the progression of liver steatosis. Previous studies determined that hepatocyte-specific deficiency of angiotensinogen (AGT), the unique substrate of the renin-angiotensin system (RAS), alleviates WD-induced hepatic steatosis in mice. However, the effects of hepatic AGT deficiency were not mimicked by pharmacological inhibition of the RAS, and the molecular mechanisms by which AGT deficiency protects against WD-induced steatosis is unknown. Therefore, liver transcriptomes were compared between hepatocyte-specific AGT-deficient mice (hepAGT -/-) and their wild-type littermates (hepAGT +/+) after 14 days of WD feeding. Gene ontology analyses showed that upregulated genes in hepAGT -/- mice were enriched for metabolic processes and downregulated genes were enriched for cell division pathways. The integration analysis of the two RNA sequencing data identified 5 key genes, Smpd3, Dtl, Cdc6, Mki67, and Top2a, which were primarily associated with cell division processes in hepAGT +/+ mice and were suppressed in hepAGT -/- mice. In conclusion, hepatic AGT deficiency downregulated genes related to cell division during the progression of liver steatosis.

With obesity reaching epidemic proportions worldwide, its impact on thyroid function is gaining increasing attention. Epidemiological studies show an association between obesity, hypothyroidism, and circulating thyroid antibodies but experimental research is needed to investigate the mechanisms underlying these associations. This study aimed to investigate thyroid function indicators in male and female rats subjected to a high-calorie diet for 16 weeks. We assessed mass-metric indices, blood biochemical markers, thyroid morphometry, and tissue concentrations of triglycerides, malonic dialdehyde (MDA), and thyroperoxidase (TPO) activity. The results revealed biochemical features of metabolic syndrome, including elevated thyroxine (T4) levels in peripheral blood. Morphological analysis indicated steatosis and thyroid hypofunction, with increased triglyceride accumulation, decreased TPO activity, and lower MDA levels in the thyroid tissue. These findings suggest that visceral obesity in male and female rats promotes early signs of thyroid dysfunction, potentially leading to hypothyroidism.

The integration of clinical, biochemical, radiological, and pathological data is crucial for diagnosing and managing pituitary adenomas (PAs). The objective of the study is to compare the clinical and biochemical classifications of PAs with their histopathological findings to improve diagnosis and treatment. This study characterized the clinical, hormonal, and pathological profiles of 40 patients with histologically confirmed PAs. Histopathological analysis identified eosinophilic adenomas in 75% of cases, amphophilic adenomas in 15%, and basophilic adenomas in 10%. Hormonal profiling revealed 22.5% prolactinomas, 15% somatotroph adenomas, 0.5% Cushing disease, and 57.5% non-functioning adenomas. Morphologically, tumors exhibited solid (55%), trabecular (30%), and papillary (15%) growth patterns. Immunohistochemical (IHC) analysis revealed monohormonal secretion in 31.5%, mixed growth hormone/prolactin secretion in 39.4%, and plurihormonal secretion in 28.9% of cases. In conclusion, this study highlights prolactinomas as the most prevalent subtype, underscoring the critical role of integrating histopathological and IHC findings for accurate diagnosis and classification of adenomas.

Platelets perform many important bodily functions, with their primary task being the prevention of bleeding by facilitating hemostasis. While platelets protect the body from blood loss, they also contribute to the development of serious diseases, such as atherosclerosis and its complications. Understanding the dual role of platelets is crucial for developing new treatments aimed at reducing thrombotic risk while improving the prognosis for patients with cardiovascular diseases. Specifically, elucidating the mechanisms underlying platelet activation may facilitate the development of selective agents that inhibit pathological platelet activity without compromising their protective function. In this context, the present study evaluated the antiplatelet activity of newly synthesized fluorophenyl-substituted 2-isoxazoline-5-carboxylic acids and their derivatives. Results showed that all compounds demonstrated the ability to suppress platelet aggregation. Increasing the concentration of the active substance from 1 to 25 mmol/L enhanced the inhibitory effect of the compounds. Methyl esters, compared to derivatives with a free carboxyl group, exhibited a stronger ability to suppress the activation of platelet receptors glycoprotein (GP) IIa/IIIb, thereby inhibiting their binding to fibrinogen and subsequent aggregation. The half-maximal inhibitory concentration values for two of the studied compounds were 7.5 mmol/L (methyl ester of 3-[3-fluorophenyl]-2-isoxazoline carboxylic acid) and 12.5 mmol/L (methyl ester of 3-[2-fluorophenyl]-2-isoxazoline carboxylic acid), respectively. In conclusion, the findings of this study indicate that 3-aryl-2-isoxazoline-5-carboxylic acids and their methyl esters, containing a single fluorine atom in the aryl group, effectively suppress the activation of platelet receptors GPIIa/IIIb.