Gut microbiota has increasingly been shown to exert effects beyond the gastrointestinal tract, some of which are mediated through its metabolites, such as trimethylamine N-oxide (TMAO)—a compound converted by gut bacteria from dietary choline found predominantly in animal products that is associated with cardiovascular disease (CVD). However, a significant gap persists in human clinical trials assessing its potential causal role. This narrative review aims to present the current understanding of the gut microbiome, TMAO, and their relationship with CVD, while proposing future directions that may support the use of TMAO as a biomarker and guide potential interventions to reduce its harmful impact. Both animal and human studies have demonstrated a link between TMAO and CVD, with animal studies also indicating a causal effect—showing increased cardiovascular risk following TMAO administration and reduced risk when TMAO is eliminated. While direct extrapolation from animal models to humans is limited due to biological differences, these findings offer a foundation for the development of well-designed clinical trials in human populations. Although direct approaches to target TMAO—such as trimethylamine (TMA) lyase inhibitors and antisense oligonucleotide (ASO) therapy—have shown promising results in animal studies, they have yet to be investigated in human trials, leaving indirect strategies such as dietary changes and probiotics as the only currently available options.

Cancer is a leading cause of death globally, claiming millions of lives each year. Despite the availability of numerous anticancer drugs, the need for new treatment options remains essential. Many current therapies come with significant toxicity, lead to various side effects, or do not consistently deliver the expected therapeutic results. Purines and pyrimidines are fundamental building blocks of nucleic acids and play crucial roles in cellular metabolism and signaling. Recent advances in medicinal chemistry have led to the development and synthesis of various derivatives that exhibit selective cytotoxic effects against cancer cells while minimizing toxicity to healthy tissues. Purine and pyrimidine scaffolds, due to their well-established biological roles and structural versatility, have emerged as key pharmacophoric fragments in anticancer drug discovery. In recent years, the rational design of hybrid molecules incorporating these heterocycles has shown promise in overcoming drug resistance, improving target selectivity, and enhancing pharmacological profiles. Purine and pyrimidines scaffolds hold significant potential as foundations for novel antitumor drugs, with established representatives in cancer treatment, including 5-fluorouracil, cladribine, capecitabine, and several others. In addition, the article discusses the challenges and future developments of purine and pyrimidine derivatives and hybrid molecules as antitumor drugs and emphasizes the need for continued research to optimize their effectiveness and reduce side effects. Overall, the innovative use of these compounds represents a major advance in targeted cancer therapy and holds promise for improving the therapeutic efficacy of malignant diseases.

The root of metabolic disease lies in the gastrointestinal tract, where nutrient absorption occurs. Within this environment, a diverse community of microorganisms exerts effects that extend beyond the intestinal barrier. Akkermansia muciniphila (A. muciniphila), one such bacterium, has been associated with enhanced intestinal integrity, reduced intestinal inflammation, weight loss, and improved insulin sensitivity, mediated through mucus fermentation, production of short-chain fatty acids (SCFAs), bacterial proteins, and extracellular vesicles (EVs). Research in this field is promising, yet far from perfect. Its clinical applicability remains limited by factors such as strain variability, scarcity of human intervention studies, and the lack of established causality. While associations have been consistently observed in both rodent and human studies, causality has thus far been demonstrated only in animal models. This issue is of critical importance, as metabolic disease remains highly prevalent, carries systemic consequences, and imposes a substantial burden on healthcare systems, underscoring the urgent need for alternative therapeutic strategies. The aim of this narrative review is to synthesize current knowledge on A. muciniphila and to highlight the key limitations consistently reported in the literature. By addressing these factors, the review seeks to provide realistic perspectives on its therapeutic potential and to outline directions for future research.

Peri-implantitis, a common biological complication of dental implants, is characterized by soft-tissue inflammation and progressive bone loss. Oxidative stress is increasingly implicated in its pathogenesis, yet the diagnostic potential of salivary redox biomarkers remains unclear. This study’s objective was to assess the association between salivary malondialdehyde (MDA) and total antioxidant capacity (TAC) and peri-implant disease via a pre-registered, quantitative meta-analysis of previously published studies using predefined statistical criteria. Following a priori PROSPERO registration, we systematically searched PubMed, Scopus, and Web of Science (2004–September 2025), extracted data in duplicate, and pooled effects using random-effects models; certainty of evidence was appraised with GRADE (Grading of Recommendations Assessment, Development and Evaluation) and risk of bias with ROBINS-I (Risk Of Bias In Non-randomized Studies of Interventions)/QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies-2). Twelve studies were included qualitatively: seven (n = 726) contributed to MDA and five (n = 485) to TAC meta-analyses. Peri-implant disease was associated with elevated MDA (SMD = 1.64, 95% CI 1.39–1.88) and reduced TAC (SMD = −1.88, 95% CI −2.17 to −1.58); statistical heterogeneity was not detected, and results were robust to sensitivity and exploratory assay-based subgroup analyses. Salivary MDA and TAC show consistent, large, standardized differences in peri-implant disease; however, observational designs, assay variability, and the absence of validated diagnostic thresholds warrant cautious interpretation and prospective validation before clinical adoption.

Background: Type 1 diabetes (T1D) is a chronic autoimmune disorder characterized by the destruction of pancreatic β-cells, leading to absolute insulin deficiency. Despite advancements in insulin therapy and glucose monitoring, achieving optimal glycemic control remains a challenge. Emerging technologies and novel therapeutic strategies are transforming the landscape of T1D management, offering new opportunities for improved outcomes. Methods: This review synthesizes recent advancements in T1D treatment, focusing on innovations in continuous glucose monitoring (CGM), automated insulin delivery systems, smart insulin formulations, telemedicine, and artificial intelligence (AI). Additionally, we explore biomedical approaches such as stem cell therapy, gene editing, immunotherapy, gut microbiota modulation, nanomedicine-based interventions, and trace element-based therapies. Results: Advances in digital health, including CGM integration with hybrid closed-loop insulin pumps and AI-driven predictive analytics, have significantly improved real-time glucose management. AI and telemedicine have enhanced personalized diabetes care and patient engagement. Furthermore, regenerative medicine strategies, including β-cell replacement, CRISPR-based gene editing, and immunomodulatory therapies, hold potential for disease modification. Probiotics and microbiome-targeted therapies have demonstrated promising effects in maintaining metabolic homeostasis, while nanomedicine-based trace elements provide additional strategies to regulate insulin sensitivity and oxidative stress. Conclusions: The future of T1D management is shifting toward precision medicine and integrated technological solutions. While these advancements present promising therapeutic avenues, challenges such as long-term efficacy, safety, accessibility, and clinical validation must be addressed. A multidisciplinary approach, combining biomedical research, artificial intelligence, and nanotechnology, will be essential to translate these innovations into clinical practice, ultimately improving the quality of life for individuals with T1D.

In the context of thermal injury, local tissue integrity and systemic homeostasis are compromised, often resulting in delayed healing, infections, and disturbances of the skin and intestinal microbial balance. Despite several reviews addressing probiotics in wound healing, none has specifically focused on their role in thermal injuries and burn-associated pathophysiology. This review uniquely integrates evidence on the gut–skin axis, postbiotic innovations, and regenerative perspectives tailored to burn care. We conducted a critical synthesis of recent preclinical and clinical trials evaluating the use of probiotics and their derivatives to promote tissue regeneration following burn injury. Previous reviews have addressed probiotics in general wound repair, but the present synthesis advances the field by bridging mechanistic insights (immune modulation, angiogenesis, microbiome restoration) with translational evidence in burn patients, offering a framework for personalized regenerative approaches. Based on a structured review of the literature—including in vitro models, animal experiments, and randomized trials with topical, enteral, and systemic administration of probiotic—we identified four main mechanisms of action: modulation of the immune response by balancing cytokines and polarization of T lymphocytes; stimulation of tissue repair by increasing the proliferation of keratinocytes and fibroblasts, increased collagen synthesis, and induction of angiogenesis; direct antimicrobial activity against biofilms and multiresistant pathogens; and the restoration of eubiosis with the improvement of the function of epithelial barriers. While these findings endorse the adjunctive use of probiotics in burn management, large multicenter trials are required to standardize strains, dosages, and formulations before their routine clinical adoption.