Hyperammonemic encephalopathy is an uncommon but potentially life-threatening and reversible cause of acute altered sensorium, most often associated with hepatic dysfunction but increasingly recognized in patients receiving chemotherapy. We report the case of a 50-year-old woman who developed progressive disorientation and reduced responsiveness one hour after completing her first cycle of FOLFOX-6 (5-fluorouracil, leucovorin, and oxaliplatin) following hemicolectomy for splenic flexure carcinoma. Initial neuroimaging and infectious workup were unremarkable. Despite correction of transient renal dysfunction, neurological status did not improve. Serum ammonia was markedly elevated, and a diagnosis of non-hepatic hyperammonemic encephalopathy secondary to chemotherapy was made. Prompt discontinuation of FOLFOX and initiation of lactulose resulted in rapid and complete clinical recovery. This case highlights the importance of early recognition of chemotherapy-induced metabolic encephalopathy, particularly fluoropyrimidine-associated toxicity, and emphasizes serum ammonia estimation in unexplained post-chemotherapy neurological deterioration to ensure timely management and favorable outcomes.

5-Fluorouracil (5-FU) is an effective chemotherapeutic agent; however, its clinical use is frequently limited by toxicity in normal tissues, including the lungs. This study investigated the prophylactic protective effect of trigonelline (TRIG), a naturally occurring alkaloid, against 5-FU-induced pulmonary injury, with particular emphasis on oxidative stress, inflammation, and apoptosis. Twenty-eight male Sprague-Dawley rats were randomly assigned to four groups (n = 7): Control, TRIG, 5-FU, and TRIG + 5-FU. TRIG (50 mg/kg) was administered orally for seven consecutive days before a single intraperitoneal injection of 5-FU (100 mg/kg). Pulmonary injury was evaluated using biochemical, histopathological, and immunohistochemical analyses. Administration of 5-FU reduced body weight gain, increased relative lung weight, disrupted oxidant-antioxidant homeostasis, and induced histopathological alterations in lung tissue. These changes were accompanied by increased TNF-α, NFκB-p65, MAPK, and Bax expression together with decreased Bcl-2 expression, indicating activation of inflammatory and apoptotic pathways. Prophylactic TRIG administration restored oxidant-antioxidant balance, suppressed TNF-α, NFκB-p65, MAPK, and Bax expression, increased Bcl-2 expression, and markedly improved histopathological findings, demonstrating attenuation of oxidative stress, inflammation, and apoptosis. TRIG protects against 5-FU-induced pulmonary injury through coordinated antioxidant, anti-inflammatory, and anti-apoptotic mechanisms. These findings provide experimental evidence supporting the prophylactic use of TRIG as a potential adjunctive strategy for reducing chemotherapy-associated pulmonary toxicity. Further experimental and preclinical studies are warranted to validate its efficacy, elucidate its molecular targets, and evaluate its translational potential.

Colorectal cancer (CRC) is one of the most common malignant neoplasms worldwide, being the third most frequently diagnosed cancer and the second leading cause of death. Due to the high incidence of CRC cases, its biological complexity, and high morbidity and mortality, the development of more effective and less aggressive therapeutic approaches is an urgent need. Extracellular vesicles (EVs), especially EXs, are a very viable alternative as a nanocarrier for anticancer molecules for the treatment of CRC, as EXs are biologically relevant EVs with considerable therapeutic potential. EXs are nanoscale vesicles approximately 30-200 nm in diameter, identical in composition to the membrane of their parent cells, and carry a bioactive cargo of proteins, lipids, nucleic acids, and glycoconjugates. Beyond their physiological functions, EXs are gaining prominence as next-generation drug delivery platforms. Their ability to improve the efficacy of antitumor therapies, potentially reducing adverse effects associated with conventional chemotherapy and radiotherapy, makes them very promising. Furthermore, functionalizing the surface with targeting ligands, such as MUC1 aptamers, AS1411, or iRGD peptides, can further increase its specificity for CRC cells. Advances in drug delivery techniques, including passive incubation, electroporation, and chemical modification, have enabled the incorporation of conventional chemotherapeutic agents such as doxorubicin, 5-fluorouracil, and SN-38, as well as nucleic acid-based therapies, including microRNA and siRNA. Due to the limitations and invasive nature of current treatments for CRC, new studies to obtain innovative and targeted therapeutic strategies are essential to reduce harmful effects. Therefore, exosome-based drug delivery systems represent a promising and clinically relevant avenue for future cancer therapy.

Maintaining the efficacy of β-lactam antibiotics against Staphylococcus aureus is a clinical priority given the prevalence of methicillin-resistant S. aureus (MRSA). We previously showed that the pyrimidine analogs 5-fluorouracil (5-FU) and 5-fluorouridine (5-FUrd) synergize with β-lactams. Here, we extended this by evaluating additional nucleotide metabolism-targeting agents. Gemcitabine (Gem) and mitomycin C (Mito), such as 5-FU and 5-FUrd, exhibited intrinsic anti-MRSA activity and potentiated β-lactams, whereas the purine analog 6-thioguanine (6-TG) showed distinct, often antagonistic effects. Transcriptomic analysis revealed that pyrimidine-targeting agents repress lysine and glutamate biosynthesis, while 6-TG induced these pathways, implicating amino acid metabolism in β-lactam potentiation. Consistent with this, pyrimidine analogs also suppressed GlmS expression, potentially limiting UDP-GlcNAc production required for cell wall synthesis, and synergized with fosfomycin. Fluorescence microscopy confirmed that the potentiation of oxacillin activity by pyrimidine-targeting agents, but not 6-TG, was accompanied by impaired peptidoglycan synthesis. Additionally, glutathione-mediated attenuation of killing implicated reactive oxygen species in the bactericidal activity of cloxacillin combinations. Finally, these agents displayed strong antibiofilm activity, further enhanced in combination with daptomycin and rifampicin. Together, these findings highlight the potential of pyrimidine analogs to potentiate cell wall-targeting antibiotics and identify an important role for modulation of cell wall precursor pathways in this anti-MRSA activity.

This study evaluates the antimicrobial properties of Juniperus phoenicea L. against multidrug-resistant microbes, highlighting potential synergistic effects of combining the J. phoenicea L. newly synthesized nanoparticles with conventional antibiotics and anticancer agents. Juniperus phoenicea L. ethanolic and ethyl acetate extracts were prepared. Antibacterial activity against a panel of multidrug-resistant microbes showed the ethanolic extract as superior to the ethyl acetate extract, with Acinetobacter baumannii being the most susceptible organism (minimum inhibitory MIC = 12.5 µg/mL). Phytochemical profiling of the ethanolic extract revealed predominant components, namely: Apigenin-7-glucoside, α-pinene, and Cedrol. Network pharmacology-based analysis suggested the potent effect of these compounds as anticancer and antibacterial agents. J. phoenicea L. nanoparticles were synthesized by a combined hot-melt dispersion and homogenization approach. Characterization yielded a zeta vesicle size of 98.6 nm, PDI 0.23, zeta potential + 48.5 mV, EE% 92.4%, and TEM size 76.2 nm. The nanoparticles markedly enhanced antibacterial activity (MIC = 6.25 µg/mL) with complete eradication of A. baumannii after 16 h. The combination with Amoxicillin and Cefoxitin showed synergistic effects. In anticancer assays, nanoparticles outperformed Fluorouracil, with IC50 = 9.05 ± 0.49 µg/mL (≈ 8.7-fold higher anticancer potency than the crude extract). The Fluorouracil-nanoparticle combination further reduced IC50 to 6.12 ± 0.41 µg/mL. Hence, it was concluded that J. phoenicea L. ethanolic extract exhibits potent antibacterial and anticancer properties and provides an effective nanoparticle precursor. Synergistic interactions with antibiotics and Fluorouracil suggest a multifaceted therapeutic strategy against infections and cancer, meriting further in vivo studies and mechanistic exploration.

Wernicke encephalopathy (WE) is an acute neurologic disorder caused by thiamine deficiency. A 55-year-old Caucasian female patient undergoing treatment with neoadjuvant folinic acid, fluorouracil, and oxaliplatin for locally advanced rectal adenocarcinoma presented with intractable nausea and vomiting resulting in clinically significant weight loss and malnutrition. Oculomotor dysfunction and gait disturbance were noted, and empiric treatment for WE was initiated with high-dose intravenous thiamine. A contrast-enhanced MRI brain was obtained and showed no acute abnormality. Diagnosis was confirmed by therapeutic response to thiamine in conjunction with a low serum thiamine level.

Hypertrophic scar (HS) is a fibrotic disorder caused by imbalanced tissue repair after skin injury. Its core features include persistent inflammation and excessive collagen deposition. Current clinical treatments are limited by poor efficacy, severe local adverse reactions, and low transdermal delivery efficiency of topical drugs. In this study, a pH-responsive borax-dextran hydrogel (TA/5-FU@BDHs) co-loaded with triamcinolone acetonide (TA) and 5-fluorouracil (5-FU) was developed for transdermal treatment of HS. First, (2-hydroxypropyl)-β-cyclodextrin (HP-β-CD) was used to prepare HP-β-CD@TA/5-FU inclusion complexes, taking advantage of its hydrophobic cavity to encapsulate TA and 5-FU, thereby enhancing the aqueous solubility and stability of the two drugs. The inclusion complexes were encapsulated into a borax-cross-linked dextran hydrogel, forming a composite carrier for pH-responsive drug release and efficient transdermal delivery. The physicochemical properties of the inclusion complexes and hydrogel were systematically characterized by particle size and zeta potential analysis, storage stability testing, X-ray diffraction (XRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and swelling and degradation behavior assessment. It enabled rapid drug release in the weakly acidic HS microenvironment, significantly promoting transdermal absorption and cellular uptake. In vitro and in vivo studies demonstrated that TA/5-FU@BDHs induced macrophage polarization from M1 to M2 phenotype by modulating inflammatory mediators, exerting anti-inflammatory effects. Meanwhile, it inhibited abnormal activation of hypertrophic scar fibroblasts (HSFs) and downregulated the expression of fibrosis-related proteins. In summary, TA/5-FU@BDHs enable precise pH-responsive release, effectively ameliorate the core pathological processes of HS via macrophage polarization, and exert anti-inflammatory and antifibrotic effects. This system provides a safe, effective, and clinically translatable strategy for transdermal local treatment of HS.