caffeine citrate (Cafnea)

Monitoring and dose adjustment of regional citrate anticoagulation for continuous renal replacement therapy.

Yessayan Lenar L, Szamosfalvi Balazs B, Tolwani Ashita A

Regional citrate anticoagulation (RCA) is the preferred anticoagulation strategy for many patients receiving continuous renal replacement therapy (CRRT). Safe implementation requires a coordinated prescription integrating citrate delivery, citrate removal within the extracorporeal circuit, individualized calcium replacement, CRRT fluid composition, and structured biochemical monitoring. This review summarizes practical approaches to RCA prescription, monitoring, and dose adjustment, emphasizing recent advances in citrate kinetics, calcium homeostasis, impaired citrate metabolism, metabolic complications, and systems-based safety. Randomized trials and meta-analyses continue to demonstrate that RCA prolongs circuit life and reduces bleeding compared with systemic heparin anticoagulation, although a mortality benefit has not been demonstrated. Recent studies have refined understanding of citrate dose, systemic citrate load, first-pass citrate extraction, individualized calcium replacement based on anticipated effluent calcium losses, and recognition of impaired citrate metabolism. They also support baseline ionized calcium assessment before CRRT initiation, integration of lactate trends into assessment of citrate metabolism, individualized CRRT fluid selection, and distinguishing true citrate accumulation from other metabolic effects of RCA. RCA is most effectively managed as an integrated CRRT prescription in which citrate delivery and removal, individualized calcium replacement, CRRT fluid composition, and operational parameters are coordinated to optimize circuit anticoagulation while maintaining electrolyte and acid-base homeostasis. Prescription adjustment should focus on four recurring clinical scenarios: inadequate circuit anticoagulation, negative calcium balance, excessive bicarbonate generation from citrate metabolism, and impaired citrate metabolism. Standardized protocols, structured monitoring, staff training, and workflow integration remain central to safe RCA implementation.

Caffeine and Cardiovascular Health: What the Science Says.

Rubin Rita R

Electrospun Zein/hydroxypropyl methylcellulose/silver citrate nanofibres with enhanced thermal and morphological stability for wound healing.

Aguila Marco Antonio Lopez MAL, Jia Jiaojiao J, Xu Yingde Y, Liang Yanqin Y et al.

Wound dressing is a critical in wound healing, yet natural electrospun nanofibres often lack thermal and morphological stability, limiting clinical utility. To address this, Zein nanofibrous mats with silver citrate nanorods (AgCit) were fabricated by electrospinning, crosslinked with citric acid (catalysed by sodium hypophosphite), and reinforced with hydroxypropyl methylcellulose (HPMC). FE-SEM revealed bead-free fibres at 5 mM AgCit, 40 wt% Zein, and 0.5 wt% HPMC, with an average diameter of 930 ± 5.5 nm. Morphological stability was achieved by HPMC reinforcement and AgCit, which prevent fibre collapse under aqueous immersion, while crosslinking was insufficient. Thermal stability was enhanced by citrate-Zein interactions and compact chain packing induced by HPMC, as confirmed by DSC (Tg1 above 100 °C) and TGA (reduced degradation rates). These strategies provided dual advantages: resilience under physiological conditions and improved durability during processing. Cell assays demonstrated cytocompatibility, proliferation, and migration, with AgCit supporting wound closure. Time-kill curves showed a 90.67 ± 0.49% and 92 ± 0.96% of antibacterial efficiency against E. coli and S. aureus, respectively within 9 h. The mechanism involves hydrogen bonding and chain entanglement between Zein and HPMC, reinforced by citrate crosslinking, while AgCit contributes antibacterial activity and HPMC provides antioxidant effect.

Mitochondrial metabolite transporters at the crossroads of metabolic reprogramming, epigenetic regulation and therapeutic vulnerabilities in colorectal cancer.

S Kaviya K, Arockiasamy Sumathy S, Srinivas K Satish KS, Shirley Sundersingh S

Metabolic reprogramming is a defining hallmark of CRC. The Warburg effect is the principal metabolic feature of CRC cells, wherein glucose is preferentially catabolized into lactate to sustain accelerated proliferation. In parallel, CRC cells exhibit strong glutamine reliance to replenish tricarboxylic acid (TCA) cycle intermediates required for adenosine triphosphate (ATP) production, lipid biosynthesis and redox homeostasis. Consequently, mitochondria play a central role in supporting the augmented biosynthetic and energetic demands beyond basal energy homeostasis. In this regard, the mitochondrial pyruvate carrier (MPC), mitochondrial citrate carrier (CIC) and the mitochondrial glutamine carrier (SLC1A5_var) located in the inner mitochondrial membrane, are emerging areas of investigation in CRC metabolism. MPC is frequently lost or downregulated in CRC, whereas CIC was found to be upregulated and promote CRC growth and survival. In contrast, SLC1A5_var has been reported to exhibit elevated expression in colon cancer cells. Recent evidence indicates that its inhibition reduces CRC cell viability; however, its specific role in CRC progression remains to be elucidated. Notably, these transporters may influence the metabolic-epigenetic landscape of CRC through metabolite-dependent regulation of chromatin and transcriptional processes. This review highlights current insights into mitochondrial metabolite transporters in CRC and their potential metabolic and epigenetic implications. Thus, elucidating the roles of these transporters may provide novel therapeutic strategies for CRC management.