Joachim Kavalakatt

Cholesterol acts as a metabolic cue that reshapes diverse signaling networks, including hedgehog and several sterol-regulated pathways orchestrated by key proteins, including sterol regulatory element-binding protein 2 (SREBP2), sterol O-acyltransferase 1 (SOAT1), Niemann–Pick type C1 (NPC1), and proprotein convertase subtilisin/kexin type 9 (PCSK9). Research over the past decade has highlighted cholesterol metabolism as a key modulator of cancer development and a promising therapeutic target. By integrating mechanistic and translational evidence, this review seeks to clarify how cholesterol metabolism interfaces with oncogenic signaling and set directions for future investigation. Accumulating preclinical and clinical data suggest that dysregulated cholesterol levels, often associated with high-fat diets, may contribute to tumorigenesis and malignant transformation. Implicated pathways, such as SREBP, NPC1, PCSK9, and SOAT1, orchestrate various processes of lipid metabolism, including cholesterol synthesis, esterification, receptor degradation, and transport, that harbor a tumorigenic environment and promote oncogenic processes. Additionally, these enzymes and corresponding pathways provide a promising direction for developing metabolism-oriented anticancer strategies. Cholesterol metabolism dysregulation serves as a major avenue for cancer signaling and growth, but studies also highlight key molecular mechanisms and targets for future treatments. Future studies should focus on expanding studies into further cancer types, investigating combination therapies, and developing novel inhibitors of key molecular targets.

Cancer remains a major global health concern, and thus, there is a growing demand for efficient and selective therapies with low systemic toxicity. Natural bioactive compounds have emerged as promising alternatives, and terpenoids have shown notable anticancer properties. They exert antiproliferative, proapoptotic, anti-invasive, and antimetastatic effects through the regulation of multiple molecular targets and signaling pathways, including modulation of apoptosis, suppression of angiogenesis, and inhibition of tumor-promoting inflammation. However, their clinical translation is constrained by poor aqueous solubility, low bioavailability, rapid systemic clearance, and inadequate tumor accumulation. Recent advances in nanotechnology offer strategies to overcome these limitations. Nanocarrier-based systems improve the solubility, stability, and pharmacokinetics of terpenoids, while enabling tumor-targeted delivery and controlled release. Various strategies, such as enhanced permeability and retention effect, ligand-mediated active targeting, and stimuli-responsive release have been used to achieve selective tumor accumulation and improved therapeutic outcomes. The purpose of this review is to provide a comprehensive evaluation of nanoformulated terpenoids in cancer with a special emphasis on their therapeutic applications and mechanisms of action. Preclinical studies demonstrate that nanocarrier-loaded terpenoids significantly increase bioavailability, enhance apoptosis, and suppress tumor angiogenesis compared with free terpenoids. The incorporation of artificial intelligence and machine learning further holds promise for the rational design of nanomedicines, accelerating their path toward clinical translation. Collectively, these developments position nanoformulated terpenoids as a powerful platform in precision oncology with strong potential for future application in cancer therapy.

Background: High blood pressure (hypertension) disproportionately affects African American/Black (Black) women. Previous research suggests that self-managing hypertension may be challenging, yet mobile applications (apps) can help to empower patients and increase medication adherence. We developed questions to test the usability of evaluating the WHISE (Wellness, Hypertension, Information Sharing, Self-Management, Education) mobile app for Black women with hypertension. Methods: Fifteen participants completed usability testing; five were potential app users (Black women with hypertension); each invited two of their peers to participate. Each testing session (n=5) included a brief overview of the app, time for participants to complete surveys and have an active discussion about the app (concurrent and retrospective think-aloud, concurrent and retrospective probing, per usability.gov), and observation of participants’ body language during the session. Testing sessions were designed to familiarize participants with the app’s features and examine their navigating ability. Results: The app received overwhelmingly positive feedback, with 80% of participants finding it to be a valuable tool in hypertension management. Participants praised the app’s user-friendliness and educational value, with one stating, ‘It is a good educational piece for helping people manage hypertension, at least to understand its basics.’ Another participant highlighted the potential for community support, saying, ‘Having a community, having some people to be accountable, to check in with and see how things are going, could encourage and motivate people to be more diligent about managing their hypertension.’ Some participants also provided constructive feedback, suggesting font size adjustments (73%) and color scheme changes (60%) for certain screens. Conclusions: Based on the feedback we received, we were able to mitigate the participants’ concerns about font size and color and create tutorial videos to guide future users in using the app. We completed these changes prior to deploying the app in our randomized clinical controlled trial.