Victória Dogani Rodrigues

Background: Artificial intelligence (AI) is increasingly being integrated into insulin management through decision-support systems, adaptive bolus calculators, conversational platforms, and automated insulin delivery (AID) technologies. However, the clinical effectiveness and safety of AI-assisted insulin management remain uncertain. Objective: To systematically evaluate evidence from randomized controlled trials (RCTs) investigating AI-assisted insulin management systems in individuals with type 1 or type 2 diabetes. Methods: A systematic literature review was conducted following PRISMA guidelines. PubMed/MEDLINE, Embase, and Cochrane CENTRAL were searched for RCTs evaluating AI-enabled insulin management interventions in insulin-treated individuals with diabetes. Eligible studies compared AI-based systems with standard care, clinician-guided insulin titration, conventional bolus calculators, or other AID algorithms. Outcomes included glycemic control, insulin titration, safety, and implementation-related measures. Owing to substantial heterogeneity, findings were synthesized narratively. Results: We included seven RCTs published between 2020 and 2025. Interventions comprised clinical decision-support systems, adaptive bolus calculators, conversational AI platforms, neural-network-based artificial pancreas algorithms, and exercise-aware AID systems. AI-assisted interventions consistently demonstrated favorable safety profiles, with no increase in severe hypoglycemia, diabetic ketoacidosis, or serious adverse events. Some systems, particularly fully automated closed-loop platforms and conversational AI-guided insulin titration, showed improvements in time in range, glucose control, adherence, and insulin optimization. User acceptance and adherence emerged as important determinants of effectiveness. Conclusions: Current randomized evidence suggests that AI-assisted insulin management systems are safe, feasible, and capable of achieving glycemic outcomes comparable to conventional care. Although certain technologies demonstrate promising clinical benefits, the evidence base remains limited by small sample sizes, short follow-up durations, and heterogeneity across interventions. Larger, long-term randomized trials are needed to establish comparative effectiveness, optimize human–AI interaction, and support broader clinical implementation.

Bergapten is a plant-derived linear furanocoumarin widely distributed in Rutaceae and Apiaceae species and increasingly recognized for its multifunctional anticancer potential. This review critically synthesizes current evidence on bergapten’s biosynthesis, physicochemical and pharmacokinetic properties, anti-inflammatory and antioxidant pharmacodynamics, and mechanistic antitumor activity, highlighting its translational relevance within pharmaceutical development. Preclinical studies across diverse malignancies demonstrate pleiotropic anticancer effects. Mechanistically, bergapten activates mitochondrial apoptosis via Bax/Bcl-2 modulation and caspase cascades, induces cell cycle arrest through p53–p21 signaling, and suppresses PI3K/Akt/mTOR and NF-κB pathways. Additional effects include PTEN-mediated autophagy induction, interference with metabolic reprogramming, reversal of multidrug resistance through ABC transporter modulation, and context-dependent photoactivated cytotoxicity. Beyond direct tumor cell targeting, bergapten attenuates pro-inflammatory mediators and regulates redox homeostasis through downregulation of NOX4-derived ROS and activation of Nrf2-driven antioxidant defenses, addressing the redox–inflammatory axis implicated in carcinogenesis. Despite promising mechanistic depth, clinical translation is limited by incomplete human pharmacokinetic data and poor aqueous solubility. Nanotechnology-enabled delivery systems and structural derivatives offer strategies to enhance bioavailability and therapeutic index. Overall, bergapten emerges as a systems-level phytochemical candidate warranting further translational investigation in oncology.

Imperatorin, a naturally occurring furanocoumarin found in several medicinal plants, has attracted considerable scientific interest due to its broad spectrum of pharmacological activities and emerging relevance in oncology. In recent years, an increasing number of experimental studies have investigated its biological effects and molecular mechanisms across different tumor models. Due to this, the review synthesizes the current preclinical and pharmacological evidence on imperatorin in cancer, with the aim of consolidating the main mechanistic pathways involved in its antitumor activity, identifying its therapeutic opportunities, and highlighting existing challenges and future research perspectives. Available in vitro and in vivo studies demonstrate that imperatorin exerts multi-targeted antitumor effects, including the induction of apoptosis, inhibition of proliferation, suppression of angiogenesis, modulation of oxidative stress, attenuation of inflammation, and disruption of oncogenic signaling pathways such as PI3K/Akt, MAPK, mTOR, and NF-κB. Imperatorin also influences the tumor microenvironment by reducing pro-inflammatory mediators, impairing stromal–tumor cross-talk, and enhancing immune-cell-mediated cytotoxicity. In addition, we also summarize pharmacokinetic and safety limitations that hinder clinical translation, including low oral bioavailability, extensive plasma protein binding, cytochrome P450 interactions, and insufficient toxicological data. In parallel, we highlight recent advances in the genetics and biosynthesis of imperatorin, which support perspectives for sustainable production and structural optimization of imperatorin derivatives. Finally, we outline key knowledge gaps and future directions, including improved delivery strategies, investigation of additional regulatory pathways, and more robust in vivo and translational studies, emphasizing that imperatorin remains a promising yet still incompletely characterized anticancer candidate. The review highlights the need for more comprehensive pharmacokinetic and safety assessments, as well as the development of improved delivery systems to address absorption and stability challenges. Further research into imperatorin’s effects on autophagy, ferroptosis, metabolic reprogramming, and the immune microenvironment is essential to deepen mechanistic understanding. Additionally, fully elucidating the biosynthetic enzymes responsible for imperatorin formation may facilitate sustainable production and the design of structurally optimized analogs.

Liver cancer remains a significant global health challenge, with hepatocellular carcinoma (HCC) being the most prevalent form. Despite advancements in treatment, high recurrence rates and the limited efficacy of conventional therapies highlight the need for novel interventions. Cinobufagin (CB), a bufadienolide extracted from the parotid secretion of Bufo gargarizans and B. melanostictus, has emerged as a promising compound with multiple antitumor mechanisms. This comprehensive review assesses the current evidence regarding CB and its containing medicine, cinobufacini, in liver cancer models. Cinobufacini is a traditional Chinese medicine extract, whereas CB refers specifically to one of its active components. The pharmacodynamic actions of CB include induction of apoptosis, DNA damage, inhibition of proliferation and migration, and modulation of key oncogenic pathways such as PI3K/Akt/mTOR, Akt/ERK, and AURKA-mTOR-eIF4E. Additionally, CB disrupts tumor metabolism and induces oxidative stress. Preclinical studies, both in vitro and in vivo, demonstrate significant antitumor efficacy. However, concerns remain regarding CB’s toxicity profile at high doses. This review emphasizes the therapeutic potential of CB in HCC treatment and advocates for further translational research to optimize its clinical applicability, dosage, and safety.

Background/Objectives: The objective was to analyze the effects of Dipeptidyl Peptidase-4 (DPP-4) inhibitors on glycemic control, insulin dose, and preservation of β-pancreatic function (C-peptide) in patients with type 1 diabetes mellitus (T1DM). Methods: A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, with a search in the PubMed database. Five randomized clinical trials evaluating the use of different DPP-4 inhibitors in patients with T1DM were selected, measuring parameters including glycated hemoglobin (HbA1c), C-peptide, time in glycemic target/range (TIR), and daily insulin dose. Results: HbA1c showed significant reduction in some studies and no significant alterations in others. TIR increased in one study (~77.87% → ~84.40%). C-peptide showed variable effects across studies. The insulin dose did not show a substantial reduction. Conclusions: DPP-4 inhibitors demonstrated modest benefits for glycemic control and preservation of β-cell function in T1DM, but these effects were inconsistent due to methodological heterogeneity. Standardized studies are needed to define beneficial subgroups and long-term efficacy.

Cancer remains one of the leading global health challenges, with increasing resistance to conventional therapies hindering treatment efficacy. Ligustilide, a bioactive compound derived from Ligusticum chuanxiong, has garnered attention for its multifaceted pharmacological properties, including anti-inflammatory, neuroprotective, and anticancer effects. This review comprehensively examines Ligustilide and its isomer, (Z)-Ligustilide, focusing on their anticancer potential across various cancer types. Ligustilide exerts its therapeutic effects through multiple mechanisms, including inhibition of cell proliferation, induction of apoptosis, and modulation of autophagy. Additionally, (Z)-Ligustilide has been shown to enhance drug sensitivity and modulate epigenetic regulation, providing a novel approach to overcoming chemoresistance. Despite promising preclinical results, the precise molecular mechanisms, pharmacokinetics, and bioavailability of Ligustilide remain under investigation. Future research should focus on optimizing its therapeutic applications, exploring its synergy with other chemotherapeutic agents, and assessing its potential in personalized cancer therapies. This review offers an in-depth analysis of Ligustilide’s anticancer mechanisms, its role in overcoming drug resistance, and its potential as a novel therapeutic strategy in cancer treatment.

Background/Objectives: Dyslipidemia is a global health concern. It refers to increased blood levels of LDL-C, triglycerides, and total cholesterol, accompanied by decreased blood HDL-C levels. Many pharmacological and non-pharmacological approaches have been designed to improve dyslipidemia management. However, nutritional therapies have gained more attention due to their antioxidant and anti-inflammatory properties. In this scenario, the carotenoid crocin stands out as a prominent anti-dyslipidemia phytochemical. Its unique structure permits lipid-lowering effects via various mechanisms, including the enhancement of lipid breakdown, reduction in lipid formation, bolstering of antioxidant defenses to diminish lipid toxicity, and decreased absorption of dietary fats. However, no recent systematic review or meta-analysis has addressed its anti-dyslipidemia effects with statistical power. Therefore, we aim to fill this gap with our current meta-analysis, as well as dose and time–response assessments. Methods: PubMed, SpringerLink, ScienceDirect, Cochrane, and Google Scholar databases were searched, and PRISMA guidelines were followed. Ten studies comprising eleven results were included. Results: Crocin did not improve LDL-C (0.2120, 95% CI: −0.0799 to 0.5040), HDL-C (−0.1937, 95% CI: −0.4896 to 0.1022), triglyceride (−0.2063, 95% CI: −0.5764 to 0.1638), or total cholesterol (0.1528, 95% CI: −0.1074 to 0.4129). The dose–response or time–response was also not statistically significant. Conclusions: More clinical studies with robust designs must be conducted to thoroughly assess crocin’s effectiveness in modulating lipid levels with the utmost care.

The aging process is closely linked to cognitive decline, and numerous studies have demonstrated a decrease in both the quality and quantity of sleep in the general population. Melissa officinalis (lemon balm) is a plant rich in bioactive compounds, including flavonoids, phenolic acids, and essential oils, which are responsible for its neuroprotective and antidepressant properties. Its positive effects on the sleep quality are probably, at least in part, attributable to the presence of rosmarinic acid, which modulates γ-aminobutyric acid transaminase activity. This review aimed to investigate the effects of M. officinalis on cognition and sleep quality in human clinical trials. For cognition, studies have shown that the plant improved cognitive performance and mood. In elderly individuals with mild cognitive impairment or early Alzheimer’s disease, extracts standardized in rosmarinic acid stabilized cognitive functions and reduced neuropsychiatric symptoms such as agitation. Regarding sleep, a combination of lemon balm and valerian significantly improved sleep quality in postmenopausal women. Isolated lemon balm extracts also reduced sleep disorders in cardiac patients. When compared to citalopram, lemon balm enhanced the quality of life, including sleep quality. It is concluded that lemon balm has the potential to improve cognition and sleep quality; however, robust evidence is needed, as more rigorous trials are required.

Background/Objectives: Astaxanthin, a naturally occurring carotenoid renowned for its potent antioxidant properties, has been proposed as a dietary supplement for weight management due to its potential effects on adipose tissue and skeletal muscle metabolism, as well as its anti-inflammatory properties. This meta-analysis systematically evaluated the impact of astaxanthin supplementation on body mass index (BMI) and body weight in adult populations. Methods: Comprehensive searches of reputable databases were conducted, adhering to the PRISMA guidelines, with statistical analyses performed using Jamovi. Results: The study incorporated data from nine clinical trials. Pooled results indicated no significant reduction in the context of BMI (−0.2162; 95% CI: −0.4697 to 0.0374) and a non-significant decrease in body weight (0.0230; 95% CI: −0.4534 to 0.4994) relative to control groups. The heterogeneity observed across studies was 30.1251% (p = 0.1593) for BMI and 73.3885% (p = 0.0002) for body weight management. The dose–response analysis showed no statistically significant association between astaxanthin dosage and outcomes related to BMI and body weight management. Additionally, statistical assessment of funnel plot asymmetry indicated no evidence of publication bias. Conclusions: The findings indicate that astaxanthin does not provide benefits in BMI regulation nor in weight control management, highlighting the need for additional large-scale and long-term clinical trials. This study contributes to the growing body of evidence on the role of nutraceuticals in metabolic health, providing a foundation for future clinical recommendations.

Background/Objectives: Depression is a mood disorder that causes persistent sadness and loss of interest, and its etiology involves a condition known as hypoadiponectinemia, which is prevalent in depressive individuals compared with healthy individuals and causes neuroinflammation. The use of intact adiponectin protein to target neuroinflammation in depressive moods is complex due to the difficulties associated with using the intact protein. AdipoRon, a synthetic oral adiponectin receptor agonist that targets the AdipoR1 and AdipoR2 receptors for adiponectin, has emerged in this context. Its most prominent effects include reduced inflammation and the attenuation of oxidative stress. To the best of our knowledge, no comprehensive review has addressed these results so far. To fill this literature gap, we present a comprehensive review examining the effectiveness of AdipoRon in treating depression. Methods: Only preclinical models are included due to the absence of clinical studies. Results: Analyzing the included studies shows that AdipoRon demonstrates contrasting effects against depression. However, most of the evidence underscores AdipoRon-based adiponectin replacement therapies as potential candidates for future treatment against this critical psychiatric condition due to their anti-neuroinflammatory potential, ultimately inhibiting several neuroinflammatory pathways. Conclusions: Future research endeavors must address several limitations due to the heterogeneity of the studies’ methodologies and results.