Cardiometabolic diseases, including hypertension, type 2 diabetes, dyslipidemia, and obesity, along with their cardiovascular complications, remain leading causes of morbidity and mortality worldwide, imposing significant public health, economic, and societal burdens. Conventional pharmacological therapies often show limited efficacy and increased adverse effects because they do not account for the body’s intrinsic circadian rhythms, which regulate organ function, drug absorption, and metabolism. Chronopharmacology, which aligns treatment timing with these biological rhythms, offers a strategy to enhance therapeutic outcomes. This review presents a comprehensive analysis of chronopharmacology principles applied to cardiometabolic disease management, integrating molecular, physiological, and clinical perspectives. It examines how core clock genes and tissue-specific circadian patterns influence drug action and absorption and summarizes evidence-based time-optimized interventions for hypertension, diabetes, dyslipidemia, obesity, and multimorbid patients. Furthermore, the review highlights emerging innovations, including artificial intelligence-guided dosing, circadian-biomarker-informed therapy selection, and wearable digital devices for real-time monitoring of biological rhythms. By synthesizing mechanistic and clinical insights, circadian-aligned treatment strategies are shown to improve drug efficacy, reduce adverse effects, and support the development of precision, rhythm-based therapeutics, offering a practical framework for personalized cardiometabolic disease care.

Cancer immunotherapy has revolutionized oncology by leveraging the immune system’s ability to recognize and eliminate tumor cells. Among the most impactful advances are immune checkpoint inhibitors that target the programmed death-1 (PD-1) receptor and its ligand PD-L1, which can restore T cell activity and generate durable responses across several cancer types. However, their effectiveness is limited by both primary and acquired resistance, restricting long-term benefit to a subset of patients. This review highlights current progress in cancer immunotherapy and explores emerging strategies beyond PD-1/PD-L1 blockade. Novel inhibitory and co-stimulatory immune checkpoints such as lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin mucin-3 (TIM-3), T cell immunoreceptor with Ig and ITIM domains (TIGIT), OX40, CD137 (4-1BB), and CD40 are examined for their potential to enhance anti-tumor immunity. The rationale for combining immunotherapy with chemotherapy, radiotherapy, targeted therapies, oncolytic viruses, and neoantigen vaccines is discussed in the context of overcoming resistance. Additional emphasis is placed on modifying the tumor microenvironment, targeting tumor metabolism, and overcoming stromal barriers. Advanced delivery systems such as chimeric antigen receptor (CAR) T cells, bispecific antibodies, and nanoparticle-based platforms offer improved specificity and reduced toxicity. Biomarker-guided precision immuno-oncology using tumor mutational burden, microsatellite instability, and immune gene signatures is advancing clinical decision-making. Gut microbiota modulation and artificial intelligence-based tools are also emerging as critical components in optimizing therapeutic outcomes. Collectively, this review proposes a multidimensional and personalized immunotherapy paradigm aimed at broadening clinical efficacy and overcoming resistance beyond conventional PD-1/PD-L1 inhibition. Graphical Abstract

Timely diagnosis is a crucial factor in decreasing the death rate of patients with breast cancer. BI-RADS categories IVc and V indicate a strong suspicion of cancer. The categorisation of each group is determined by the characteristics of the lesion. Certain benign breast lesions might have radiological features indicative of malignancy; thus, biopsy is mandatory. This study aimed to identify the histopathological diagnosis of benign breast masses classified into BIRADS IVc and V subgroups, investigate the radiological characteristics of these masses, and identify ultrasound features that could lead to false positive results (benign lesions that mimic malignancy on imaging). This was a retrospective cross-sectional study at a single facility. Breast lesions reported as BIRADS IVc and V that underwent needle core/stereotactic vacuum-assisted biopsy were reviewed. Patients with benign pathologic diagnoses were analysed, delineating pathological diagnoses. Radiological descriptors were compared to those of a matched control of 50 malignant cases with BIRADS IVc. A total of 828 breast lesions classified as BIRADS IVc or V were detected during the period spanning from 2015 to 2022. Forty-four lesions (44/828, 5.3%) were benign at initial biopsy, while 784 lesions (784/828, 94.7%) were malignant. After histopathological testing and repeat biopsy, 26/828 (3.14%) patients had discordant benign diagnosis. Half of the repeated biopsies (10/20, 50%) showed malignant pathology. Compared to that in the control group, the presence of an oval shape of the mass was significantly more common in patients with benign pathology (p = 0.035). Conversely, the presence of posterior shadowing was significantly less common (p = 0.050) in benign lesions. No significant differences were observed for the other radiological characteristics. The most common histopathological diagnosis was fibrocystic change. This study highlights key findings regarding the sonographic imaging descriptors and histopathological diagnoses of benign breast lesions categorised as BIRADS IVc/V. The study recommends a correlation between clinical and radiological findings and encourages multidisciplinary decision-making among radiologists, pathologists, and clinicians to determine if a repeat biopsy is warranted. There is a need for continuous research to improve the diagnosis and treatment of breast lesions and reduce false-positive rates by incorporating other methodologies such as sonoelastography and incorporating deep learning and artificial intelligence in the decision-making to eliminate unnecessary procedures.

The obesity–metabolic syndrome–diabetes continuum is driven by interconnected mechanisms including insulin resistance, dysfunctional adiposity, chronic inflammation and progressive cardio–renal–metabolic injury. This triggered a need for therapies that extend beyond glucose lowering alone. The benefits of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) as disease-modifying drugs include weight loss, cardiovascular risk reduction, glycemic control and renal protection. However, treatment burden, adherence issues and access restrictions may limit the long-term effects of injectable formulations. One significant translational development that aims to close this gap is oral GLP-1-based treatments. In this review, we examine the mechanistic rationale, formulation science and clinical development of oral GLP-1 RAs. Oral semaglutide is presented as the first validated proof of concept for systemic peptide delivery by the gastrointestinal route. The biological barriers to oral peptide absorption, including enzymatic degradation, low epithelial permeability, pharmacokinetic variability and epithelial safety constraints, are critically discussed. Enabling technologies such as SNAC-based gastric absorption, nanocarriers, mucoadhesive systems and stability-optimization platforms are evaluated. Evidence from the PIONEER program and related studies demonstrating meaningful glycemic and weight-loss efficacy, acceptable safety and clinical utility in patients with type 2 diabetes and chronic kidney disease is further synthesized. Beyond first-generation oral peptide platforms, we discuss the emerging landscape of non-peptide oral GLP-1 RAs, dual and triple incretin agonists, precision dosing strategies and model-informed drug development. Oral GLP-1-based therapeutics are shifting from a formulation breakthrough to a broader translational strategy for disease modification across the obesity–metabolic syndrome–diabetes continuum. Long-term renal outcomes, access and implementation barriers remain important priorities for future research.